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Alan Franciscus
Editor-in-Chief
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In This Issue:
Company in Hepatitis Case
Violated Rules
Study Probes A-B Residents' Health
Fludarabine May Place Patients at Risk Of Hepatitis
B From Virus Reactivation
Changes in Formularies May Lead to Discontinuation
of Drug Therapy New Findings Suggest
Stealth Merger: Drug Companies and Government
Medical Research
Liver Transplant Thwarted by Blackout Succeeds
on 2nd Try
Access To Clean Needles - A Health Issue
Micrologix licenses Hepatitis B Compound to Spring
Bank Technologies
Organetix, Inc. Announces Positive Test Results
for Hepatitis C Treatment
Insulin Resistance, Chronic Hepatitis C and
Fibrosis Progression
Judge Rules for HIV Patient in Transplant
Lamivudine Controls Viral Replication in Relapsed
Hepatitis B Patients Although Resistance Eventually Develops
Hepatitis C Virus-Positive Renal Donations Heighten
Mortality Risk
Organetix, Inc. Commences Production of A4+L,
Proprietary Liver Product
December 6th, 2003
Company in Hepatitis
Case Violated Rules
By Olga R. Rodriguez
Source: Associated Press
MONTERREY, Mexico (AP) - U.S. inspectors
visiting green-onion producers in northwestern Mexico found
that one of the four companies linked to a deadly U.S. hepatitis
outbreak failed to meet hygiene standards, Mexican officials
said Friday.
Javier Trujillo, undersecretary for food
safety and quality in Mexico's Ministry of Agriculture, said
Dos M Sales de Mexico, a company located near the border city
of Mexicali, in Baja California state, was washing its scallions
with water from a nearby reservoir, rather than with purified
drinking water, as required.
"The deficiencies where found at the
company's packing operation but that is not conclusive proof
that this was the origin of the hepatitis outbreak in the
United States," Trujillo said.
The other three companies linked to the
outbreak that killed three people and sickened more than 600
in Pennsylvania are Agricola La Laguna, a.k.a. Sun Fresh,
of Ensenada; Tecnoagro International in San Luis Rio Colorado
and Ensenada, and Agro Industrias Vigor in Tijuana, Ojos Negros
and San Quintin, Baja California.
The probe by three inspectors from the
U.S. Food and Drug Administration and one from U.S. Centers
for Disease Control and Prevention - accompanied by Mexican
officials - started Monday, and will continue next week when
inspectors will visit scallion-exporting companies not linked
to the hepatitis A outbreak, Trujillo said.
But Trujillo said the FDA rushed to judgment
by publicly identifying suspected companies before completing
an investigation that followed the green-onions through the
supply chain.
"The hypothesis that the outbreak
could have originated in Mexico is one, but there is also
the likelihood of contamination in the transportation, or
at the restaurant," Trujillo said. "It's really
surprising that the FDA would only emphasize the hypothesis
of contamination at the point of origin."
Ellen Morrison, director of the Office
of Crisis Management for the FDA, said the FDA has been very
careful with the investigation and sent the inspection team
to Mexico only after not finding sources of contamination
at the different restaurants.
She said it's premature to speak of the
inspectors' findings while the investigation is in progress.
The hepatitis strains found in the rash
of illnesses among customers at a Chi-Chi's restaurant at
the Beaver Valley Mall northwest of Pittsburgh are very similar
to those found in smaller outbreaks that occurred in Tennessee
and Georgia in September. Those earlier outbreaks were traced
to three companies known to have supplied Mexican green onions
in those states. It is unclear whether they are the same companies
currently being investigated.
Back to top
Study Probes
A-B Residents' Health
By Josh B. Wardrop / Staff Writer
Residents of Allston-Brighton are some
of the healthiest in all of Boston's various neighborhoods
- even if they're not necessarily the happiest, according
to a study by the Boston Public Health Commission.
The recent study, based on the 2000 Census,
hospital discharge files and a survey of Allston-Brighton
residents, found that rates of infant mortality, low birth
weight, hepatitis C, AIDS, HIV and sexually transmitted diseases
were all significantly lower in Allston-Brighton than in Boston
as a whole.
The study was intended to measure how Allston-Brighton
stacked up against 15 other Boston neighborhoods, and against
the city as a whole, in terms of public health issues such
as hospitalization rates, causes of death and incidence rates
for certain diseases and health problems.
"We go all over the city once a year,"
said Barbara Ferrer, deputy director of the commission, as
she presenting the results Monday at St. Elizabeth's Hospital.
"This gives us an opportunity to share information about
your neighborhood, and hear from you regarding what health
issues you're concerned about."
For the most part, the results of the BPHC
study - based on numbers from the year 2001 - revealed that
Allston-Brighton is one of the healthier communities in Boston.
In fact, Allston-Brighton had the second-lowest rates of infant
mortality (babies who die before their first birthday) with
only four deaths per 1,000 births. Only East Boston had a
lower percentage. And the STD rate for diseases such as gonorrhea,
syphilis and chlamydia - 192 cases per 100,000 residents -
was lower than any community except West Roxbury.
According to Ferrer, the study was age-adjusted, so the high
concentration of young and healthy college students in Allston-Brighton
does not explain the high marks. "The college-age community
was allowed for in this process," she said.
The overall positive results were tempered
by a few categories in which Allston-Brighton compared unfavorably
with the rest of Boston. Hospitalization for matters related
to psychoses, for example, accounted for the second highest-number
of hospitalizations in both A-B and Boston as a whole, after
pregnancy. However, the hospitalization rate for psychoses,
- seven hospitalizations per 1,000 people - was about 40 percent
higher in A-B than in Boston as a whole. Ferrer admitted that
the high concentration of halfway houses in A-B may have had
some bearing on those numbers, "especially if they report
those homes as their legal residence."
Depression also seems to strike A-B residents
in slightly greater numbers than those in other neighborhoods.
The BPHC study revealed that 10 percent of reporting A-B residents
said that they felt sad, blue or depressed for 15 or more
days out of the month, which was higher than the 8 percent
for Boston as a whole.
And obesity - a pandemic problem in America
today - is certainly a concern here in Allston-Brighton as
well. According to the BPHC study, 35 percent of A-B adult
residents are overweight or obese, which Ferrer terms "a
high rate, but actually one of the lowest in the city."
The rate for Boston as a whole is 47 percent, with communities
like Hyde Park, Mattapan and South Boston reaching 60 percent
or higher.
The high obesity numbers were attributed
to a lack of exercise. Approximately 58 percent of A-B adult
residents reported engaging in no physical exercise or in
exercise of less than 30 minutes a day, five times a week.
This was roughly equal to the numbers for Boston as a whole.
The leading causes of death in Allston-Brighton
were heart disease, at 188 deaths per 100,000 residents, followed
by cancer at 181 deaths per 100,000 residents. For Boston
as a whole, cancer was the leading cause while heart disease
came second.
Back to top
Fludarabine
May Place Patients at Risk Of Hepatitis B From Virus Reactivation
By Jill Taylor
Fludarabine, alone or in combination with
other (non-steroid) antineoplastic drugs, is a powerful trigger
of severe hepatitis due to hepatitis B (HBV) reactivation
in HBsAg-positive and anti-HBc-positive patients, say Italian
researchers.
Previous studies have shown that chemotherapy
can cause hepatitis flare-up through viral reactivation in
patients with past virus contact. An effect of fludarabine,
a nucleoside analog effective in treating indolent non-Hodgkin's
lymphoma (NHL), is profound and prolonged immunosuppression
with a decrease of CD4+ and CD8+ lymphocytes, which predisposes
to opportunistic infections.
However, little data exists regarding the
genotype of reactivated viruses. Dr. Marco Picardi of Federico
II University Medical School, Naples, Italy, and colleagues
performed a prospective study on HBV reactivation and reactivated
virus genotype in NHL patients undergoing fludarabine-based
chemotherapy.
The study included 40 consecutive adult
patients with grade I follicular, nodal small lymphocytic
or marginal zone B-cell NHL. Patients received diagnostic
tests prior to each treatment course, and monthly after chemotherapy
completion.
Prior to starting chemotherapy, patients
were assessed for HBsAg, HBeAg, and for antibodies against
HBs, HBe, HBc, Hä, HCV, HAV, cytomegalovirus, Epstein
Barr virus and herpes simplex virus. HBV-DNA and HCV-RNA were
measured by a quantitative polymerase chain reaction procedure.
Pre-treatment assessment of viral serological
status showed that 12 patients were HBV-positive, 6 were HCV-positive,
and the others were seronegative for both viruses. Among HBV-positive
patients, 4 were healthy carriers of HBsAg, 2 were anti-HBc-positive
without anti-HBs, and the remaining 6 were anti- HBs-positive
(together with anti-HBe and/or anti- HBc).
Hepatitis flare-up occurred in 4 HBsAg-positive
patients and in 1 anti-HBc-positive patient from between 1
and 4 months after chemotherapy, when the CD4/CD8 ratio was
still inverted. HBV reactivation occurred in all 5 instances.
Lamivudine was used as first-line treatment
in all 5 cases of hepatitis. Of these patients, 2 responded
to treatment, 1 died of acute liver failure, and 2 had persistent
severe hepatitis.
Interestingly, a rough correlation was
observed between clinical response to lamivudine and the degree
of genomic mutations of the corresponding etiological viral
isolate. HBV genome sequencing demonstrated that deviation
from the closest related published sequences was 1.0% and
1.1% in lamivudine-responsive patients, and 1.5%, 1.8%, and
1.7% in lamivudine-resistant patients.
The high rate of genome mutations and amino
acid substitutions at critical conserved domains and prolonged
CD4 depletion may be important factors for viral reactivation,
hepatitis severity, and lack of response to lamivudine, the
researchers conclude.
Haematologica 2003;88:1296-1303.
Back to top
Changes
in Formularies May Lead to Discontinuation of Drug Therapy
New Findings Suggest
Source: Health Daily News
Switching from a one-tier to a three-tier
formulary has a large effect on specific drug use while resulting
in increased out-of-pocket expenditures for enrollees, according
to a study appearing in the Dec. 4 issue of The New England
Journal of Medicine.
Researchers compared patterns of utilization and spending
for two large employers one year before and one year after
the employers implemented a three-tier formulary in 2000.
Employer 1 switched from a one-tier formulary to a three-tier
formulary and increased copayments across all tiers. Employer
2 made a more moderate change from a two-tier to a three-tier
formulary that involved increases in the copays for only the
nonpreferred brand name drugs that were assigned to tier three.
Separate comparison groups of enrollees covered by employers
that had a stable two-tier formulary throughout the study
period were identified for both employers.
Results showed that many enrollees covered by Employer 1 stopped
taking necessary drugs. Sixteen percent of patients using
tier three ACE inhibitors for cardiovascular disease stopped
taking the therapy versus 6 percent in the comparison group;
21 percent of patients using cholesterol-lowering statins
halted therapy versus 11 percent in the comparison group;
and 32 percent stopped taking proton-pump inhibitors (PPIs)
versus 19 percent in the comparison group.
The findings also showed a major shift in spending from the
plan to the enrollee with large increases in copays. Some
employees even switched the drug they were taking to a drug
in a lower tier; 41.6 percent, 49.4 percent and 35.1 percent
of Employer 1's enrollees initially taking tier three ACE
inhibitors, statins and PPIs, respectively, switched to a
drug of a lower tier after the policy change. In the comparison
group, the respective rates were 4.2 percent, 17.3 percent
and 1.5 percent.
For enrollees of Employer 2, the effects of formulary administration
were much smaller. Employer 2's enrollees were more likely
to switch from a non-preferred brand name drug to a less expensive
brand name or generic drug. Nearly 41 percent, 48.5 percent
and 17.6 percent of patients taking ACE inhibitors, statins
or PPIs, respectively, switched to a lower-tiered drug versus
14.9 percent, 8 percent and 2.1 percent in the comparison
group who switched.
"As three-tier formularies become increasingly prevalent,
we need much greater knowledge about these details in order
to reap the advantages in cost savings without causing deleterious
consequences for patients," the researchers said.
Back to top
December 7th, 2003
Stealth Merger:
Drug Companies and Government Medical Research
Some of the National Institutes of Health's top scientists
are also collecting paychecks and stock options from biomedical
firms. Increasingly, such deals are kept secret
By David Willman, Los Angles Times Staff Writer
BETHESDA, Md. — "Subject No.
4" died at 1:44 a.m. on June 14, 1999, in the immense
federal research clinic of the National Institutes of Health.
The cause of death was clear: a complication
from an experimental treatment for kidney inflammation using
a drug made by a German company, Schering AG.
Among the first to be notified was Dr.
Stephen I. Katz, the senior NIH official whose institute conducted
the study.
Unbeknown to the participants, Katz also
was a paid consultant to Schering AG.
Katz and his institute staff could have
responded to the death by stopping the study immediately.
They also could have moved swiftly to warn doctors outside
the NIH who were prescribing the drug for similar disorders.
Either step might have threatened the market potential for
Schering AG's drug. They did neither.
Questioned later, Katz said that his consulting
arrangement with Schering AG did not influence his institute's
decisions. His work with the company was approved by NIH leaders.
Such dual roles — federal research
leader and drug company consultant — are increasingly
common at the NIH, an agency once known for independent scientific
inquiry on behalf of a single client: the public.
Two decades ago, the NIH was so distinct
from industry that Margaret Heckler, secretary of Health and
Human Services in the Reagan administration, could describe
it as "an island of objective and pristine research,
untainted by the influences of commercialization."
Today, with its senior scientists collecting
paychecks and stock options from biomedical companies, the
NIH is no longer an island.
Interviews and corporate and federal records
obtained by the Los Angeles Times document hundreds of consulting
payments to ranking NIH officials, including:
• Katz, director of the NIH's National
Institute of Arthritis and Musculoskeletal and Skin Diseases,
who collected between $476,369 and $616,365 in company fees
in the last decade, according to his yearly income-disclosure
reports. Some of his fees were reported in ranges without
citing exact figures. Schering AG paid Katz at least $170,000.
Another company paid him more than $140,000 in consulting
fees. It won $1.7 million in grants from his institute before
going bankrupt last year.
• Dr. John I. Gallin, director of
the NIH's Clinical Center, the nation's largest site of medical
experiments on humans, who has received between $145,000 and
$322,000 in fees and stock proceeds for his consulting from
1997 through last year. In one case, Gallin co-wrote an article
highlighting a company's gene-transfer technology, while hiring
on as a consultant to a subsidiary of that company.
• Dr. Richard C. Eastman, the NIH's
top diabetes researcher in 1997, who wrote to the Food and
Drug Administration that year defending a product without
disclosing in his letter that he was a paid consultant to
the manufacturer. Eastman's letter said the risk of liver
failure from the drug was "very minimal." Six months
later, a patient, Audrey LaRue Jones, who was taking the drug
in an NIH study that Eastman oversaw, suffered sudden liver
failure and died. Liver experts found that the drug probably
caused the liver failure.
• Dr. Ronald N. Germain, deputy director
of a major laboratory at the National Institute of Allergy
and Infectious Diseases, who has collected more than $1.4
million in company consulting fees in the last 11 years, plus
stock options. One of the companies collaborated with his
laboratory on research. The founder of another of the companies
worked with Germain on a separate NIH-sponsored project.
• Jeffrey Schlom, director of the
National Cancer Institute's Laboratory of Tumor Immunology
and Biology, who has taken $331,500 in company fees over 10
years. Schlom helped lead NIH-funded studies exploring wider
use for a cancer drug — at the same time that his highest-paying
client was seeking to make the drug through genetic engineering.
• Jeffrey M. Trent, who became scientific
director of the National Human Genome Research Institute in
1993 and, over the next three years, reported between $50,608
and $163,000 in industry consulting fees. Trent, who accepted
nearly half of that income from a company active in genetic
research, was not required to file public financial-disclosure
statements as of 1997. He left the government last year.
Hidden From View
Increasingly, outside payments to NIH scientists are being
hidden from public view. Relying in part on a 1998 legal opinion,
NIH officials now allow more than 94% of the agency's top-paid
employees to keep their consulting income confidential.
As a result, the NIH is one of the most
secretive agencies in the federal government when it comes
to financial disclosures. A survey by The Times of 34 other
federal agencies found that all had higher percentages of
eligible employees filing reports on outside income. In several
agencies, every top-paid official submitted public reports.
The trend toward secrecy among NIH scientists
goes beyond their failure to report outside income. Many of
them also routinely sign confidentiality agreements with their
corporate employers, putting their outside work under tight
wraps.
Gallin, Germain, Katz, Schlom and Trent
each said that their consulting deals were authorized beforehand
by NIH officials and had no adverse effect on their government
work. Eastman declined to comment for this article.
Dr. Arnold S. Relman, the former editor
of the New England Journal of Medicine, said that private
consulting by government scientists posed "legitimate
cause for concern."
"If I am a scientist working in an
NIH lab and I get a lot of money in consulting fees, then
I'm going to want to make sure that the company does very
well," Relman said.
Relman and others in the field of medical
ethics said company payments raised important questions about
public health decisions made throughout the NIH:
• Will judgment calls on the safety
of individual patients be affected by commercial interests?
• Can study participants trust that
experimental treatments are chosen on merit and not because
of officials' personal financial interests?
• Will scientists shade their interpretations
of study results to favor their clients?
• Will officials favor their clients
over other companies that seek NIH grants or collaborations?
Conflict-of-interest questions also arise
in the potentially lucrative awarding of patents.
Thomas J. Kindt, the director of in-house
research at the National Institute of Allergy and Infectious
Diseases, accepted $63,000 in consulting fees from a New York
biotechnology company, Innovir Laboratories, and wound up
an inventor on one of its patents.
Asked why the government received no consideration,
Kindt said that he had contributed to the "basic idea"
while using vacation time.
"No work was done on it as a government
employee," said Kindt, whose annual salary at the NIH
is $191,200. His consulting with Innovir was approved by NIH
officials, Kindt said.
Others worry that the private arrangements
can undermine the public interest.
"The fact that paid consulting is
happening I find very disturbing," said Dr. Curt D. Furberg,
former head of clinical trials at the National Heart, Lung
and Blood Institute. "It should not be done."
Private consulting fees tempt government
scientists to pursue less-deserving research and to "put
a spin on their interpretation" of study results, he
said.
"Science should be for the sake of
gaining knowledge and looking for the truth," Furberg
said. "There should be no other factors involved that
can introduce bias on decision-making."
Dr. Ruth L. Kirschstein, who as the deputy
director or the acting director of the NIH since 1993 has
approved many of the top officials' consulting arrangements,
said she did not believe they had compromised the public interest.
"I think NIH scientists, NIH directors and all the staff
are highly ethical people with enormous integrity," she
said. "And I think we do our business in the most remarkable
way."
In response to The Times' findings, Kirschstein
said, she would "think about" whether administrators
should learn more about a company's ties to the NIH before
approving the consulting arrangements.
"Systems can always be tightened up,"
Kirschstein said on Oct. 29. "And perhaps, based on this,
we will do so."
On Nov. 20, NIH Director Elias A. Zerhouni
told agency leaders that he would form a committee to help
"determine the appropriateness" of employees' consulting
and other outside arrangements.
"I believe we can improve our performance
by subjecting ethics deliberations to a more transparent process,"
Zerhouni said in a memo.
In a brief telephone interview last week,
Zerhouni said he wanted the NIH "to manage not just the
reality, but the perception of conflict of interest."
"If there is something that could
be viewed as improper, I think we need to be able to advise
our scientists not to get into these relationships,"
he said. "My sense is our scientists are people of goodwill."
Temptations Abound
The NIH traces its beginnings to the Laboratory of Hygiene,
founded in 1887 within a Navy hospital on Staten Island in
New York. It became the federal government's first research
institution for confronting such epidemic diseases as cholera,
diphtheria, tuberculosis and smallpox.
The laboratory's success convinced Congress
of its value in seeking cures for diseases.
In 1938, the renamed National Institute
of Health moved to its present, 300-acre headquarters in Bethesda,
about nine miles north of the White House.
The agency's responsibilities — and
prominence — have grown steadily.
In 1948, four institutes were created to
support work on cardiac disease, infectious diseases, dental
disorders and experimental biology. "Institute"
in the agency's name became "Institutes."
President Nixon turned to the NIH in 1971
to lead a war on cancer. The agency has led the government's
fight against AIDS. Two years ago, President Bush enlisted
the NIH to help counter biological terrorism.
Republican and Democratic administrations
have boosted spending for the 27 research centers and institutes
that compose today's NIH. Since 1990, the annual budget has
nearly quadrupled, to $27.9 billion this fiscal year.
Senior NIH scientists are among the highest-paid
employees in the federal government.
With billions of dollars in product sales
potentially at stake for industry, and untold fortunes riding
on biomedical stock prices, commercial temptations abound:
Researchers poised to make a breakthrough
in their NIH labs can, the same day, land paid consulting
positions with companies eager to exploit their insights and
cachet. Many companies cite their connections to NIH scientists
on Web sites and in news releases, despite an agency rule
against the practice. Selection of a company's products for
an NIH study can provide a bankable endorsement — attracting
investors and boosting stock value. If the study yields positive
results, the benefits can be even greater.
Conflicts of interest among university
medical researchers have received wide attention in recent
years. U.S. Rep. W.J. "Billy" Tauzin (R-La.) also
raised questions recently about cash awards that several nonprofit
institutions made to a previous director of the National Cancer
Institute.
The consulting deals between drug companies
and full-time, career employees at the NIH, however, have
gone all but unnoticed.
The wide embrace of private consulting
within the NIH can be traced in part to calls from Congress
for quicker "translation" of basic federal research
into improved treatments for patients.
And for decades industry has pressed for
more access to the government's scientific discoveries.
As the number of government-held patents
soared, companies sought legislation encouraging commercialization
of federally funded inventions. The proponents said the changes
also would make U.S. firms more competitive with foreign companies
whose research and development programs were subsidized by
their governments.
Laws enacted in the 1980s for the first
time authorized formal research collaborations between companies
and scientific arms of the government, including the NIH.
Starting in late 1986, in-house researchers at the NIH were
permitted to arrange cooperative research agreements with
companies. The agreements were intended to benefit both sides
while advancing scientific discovery.
Other changes in law permitted the government
agencies, and the researchers, to share in future patent royalties
for inventions.
The new laws said nothing about government
employees being hired by the companies.
Yet by the end of the 1980s, more companies
were putting NIH researchers on their payrolls, albeit within
limits imposed by the NIH.
Agency leaders in the 1990s began weakening
those restrictions.
In November 1995, then-NIH Director Harold
E. Varmus wrote to all institute and center directors, rescinding
"immediately" a policy that had barred them from
accepting consulting fees and payments of stock from companies.
The changes, he wrote, would bring the
NIH ethics rules more in line with new, less stringent, executive
branch standards. Loosening of restrictions on employees'
outside pursuits was occurring throughout the government.
And with biomedical companies ready to hire, few were better
positioned to benefit than employees at the NIH.
Varmus' memo — which until now has
not been made public — scuttled other restraints affecting
all employees, including a $25,000 annual limit on outside
income, a prohibition on accepting company stock as payment
and a limit of 500 hours a year on outside activities.
His memo also offered a narrowed definition
of conflict of interest:
Employees had been barred from consulting
for any company that collaborated with their NIH lab or branch.
But Varmus said the ban would be applied only if the researcher
was personally involved in the company's collaboration with
the agency.
Furberg, the former NIH official, said
Varmus' actions invited, at minimum, appearances of conflict
of interest.
"I'm amazed at what he did,"
said Furberg, a professor at Wake Forest University. "And
to do it in secrecy I find very objectionable. This is a critical
change in the NIH policy."
In 1999, Varmus wrote a letter to the institute
directors that cautioned them to "avoid even the appearance
of a conflict of interest." But in an attachment to the
letter, he told them that employees "may briefly discuss
or mention current work" to outsiders, in effect giving
agency scientists permission to reveal their unpublished,
confidential research.
Varmus, now president and chief executive
of the Memorial Sloan-Kettering Cancer Center in New York,
declined to be interviewed for this article. His spokeswoman,
R. Anne Thomas, said that Varmus, who in 1989 shared a Nobel
Prize for research into the genetic basis of cancer, believed
that NIH employees should take personal responsibility for
avoiding conflicts of interest, regardless of what agency
rules allow.
Kirschstein, after taking over as Varmus'
interim successor at the NIH three years ago, said in a May
2000 speech to medical researchers that conflicts of interest
posed "a major concern."
"While the federal government was
once the dominant force for supporting clinical research,
today we share the arena with biotechnology companies, pharmaceutical
firms and many others — all interested in the possibility
of financial gain from their research.
"Profit raises issues of public trust,"
she said. "When scientific inquiry generates findings
that can make a profit for the researcher and the institution,
their images become clouded."
Yet officials have lifted controls on consulting
even as industry's stake in NIH research has deepened. When
Zerhouni, the current NIH director, appeared before the House
Subcommittee on Environment, Technology and Standards last
year, he cited 274 ongoing research and development agreements
between the federal agency and industry.
At the same time, NIH leaders have moved
to what they describe as "managing" conflicts of
interest. Employees are allowed to consult if they receive
prior clearance from an administrator at their institute or,
in the case of most institute directors, from NIH headquarters.
An Honor System
Potential conflicts are typically addressed by allowing employees
to sign "recusals." Under these agreements, NIH
employees pledge not to participate in decisions affecting
an outside client. Agency officials, Kirschstein said, rely
on an honor system to enforce recusals and other conflict-of-interest
rules.
The Times found instances in which the
recusals did not work as intended.
In the mid-to-late 1990s, Eastman, the
diabetes researcher, participated in a series of decisions
affecting the drug company employing him as a consultant,
despite having signed a recusal. Separately, Katz, the director
of the arthritis institute, signed a recusal involving his
client, Schering AG, which nevertheless supplied the NIH with
the drug involved in the kidney patient's death in 1999.
Katz said that he did not know at the time
that Schering AG was the maker of the drug his institute was
testing.
Compliance with the recusals can, itself,
undercut the interests of the NIH and taxpayers, who support
the agency. When heads of institutes and laboratories recuse
themselves, they sometimes constrain their ability to carry
out their government duties.
Kirschstein, who for the last eight years
has personally reviewed requests from the institute directors
to consult privately for pay, said she tended to approve the
deals, unless she saw "real conflict."
"I've disapproved some — and
I've approved many," she said.
In her view, recusals have worked "extremely
well" in avoiding conflicts of interest.
Other present and former officials say
it is difficult, if not impossible, for researchers to keep
separate their confidential government information when they
consult for companies.
"You can't police the thing,"
Philip S. Chen Jr., a senior advisor in the NIH director's
office who has served as an agency scientist or administrator
since the 1950s, said in an interview last year. "The
rules are there — whether they follow the rules is another
thing."
A former NIH director voiced surprise at
the agency's loosened approach to conflicts of interest.
"There has been a lot of relaxation,"
said Dr. Bernadine P. Healy, who served as director from 1991
to 1993. Before, Healy said in an interview, "there were
very strict ethics rules for NIH scientists. You couldn't
have virtually any connection with a company if your institute
was in any way doing research involving their products."
At least one vestige of the old days remains.
During last year's holiday season, workers
were advised to refuse gifts from outsiders worth more than
$20.
"Just a reminder," ethics coordinator
John C. Condray wrote, introducing a five-page memo, "that
sometimes gifts and events can create the appearance of a
lack of impartiality."
Fewer Public Filings
While making it easier for scientists to cut consulting deals,
the NIH has made it harder for the public to find out about
them.
The Ethics in Government Act requires yearly
financial-disclosure reports from senior federal employees.
This year, employees paid $102,168 or more generally must
disclose outside income by filing a "278" form,
which is available for public review. Other employees may
file a "450" form — which does not specify
the amount of money received from an outside party and is
kept confidential.
At the NIH, 2,259 employees make more than
$102,168, according to data provided by the NIH. Those records
show that 127 of the employees — about 6% — are
filing disclosure forms available to the public.
From 1997 through 2002, the number of NIH
employees filing public reports of their outside income dropped
by about 64%, according to the agency records. Most of those
employees have switched to filing the confidential 450 form.
At the National Institute of Allergy and
Infectious Diseases — which researches treatments for
AIDS and other life-threatening maladies — only three
officials file public reports revealing their outside income,
according to NIH records.
Officials at the NIH said that an advisory
legal opinion from the U.S. Office of Government Ethics gave
them the discretion to bypass public disclosure.
Issued in 1998, the opinion said that the
threshold for public disclosure was to be set, not by a federal
employee's actual salary, but by the low end of his or her
pay grade. If the minimum salary in an employee's grade is
beneath the $102,168 threshold, he or she is exempt from filing
a public report.
The NIH has shifted many of its high-salaried
employees into pay plans with minimums that dip below the
threshold.
For instance, two prominent NIH laboratory
leaders, Schlom and Germain, make $180,400 and $179,900, respectively.
Within roughly the last year, NIH changed each of their pay
plans, and they now are exempt from public disclosure.
They file confidential forms, which instruct
employees to not specify the dollar amounts they receive from
outside parties.
Asked why the NIH has assigned highly paid
staff to plans that eliminate public disclosure of employees'
outside income, an NIH spokesman, John Burklow, provided a
written response:
"The primary benefit of the alternate
pay plans is to attract and retain the best scientists in
a highly competitive environment."
Said Donald Ralbovsky, another NIH spokesman:
"What it really boils down [to] is that fewer people
are filing 278s because of changes in pay plans."
The shift imparts an implicit message to
employees, said George J. Galasso, a former NIH researcher
and administrator who retired in 1996:
"If you've got something to hide,
you file a 450. If you don't, you file a 278."
Make-or-Break Grants
As director of the National Institute of Arthritis and Musculoskeletal
and Skin Diseases, Katz is one of the few at the NIH who still
must file public financial-disclosure reports.
Katz, 62, is paid $200,000 a year —
more than members of Congress, justices on the Supreme Court
and the vice president.
His institute leads the government's research
into the causes, treatment and prevention of disorders of
the joints, bones and overall muscle-skeletal system.
With a yearly institute budget of $485.4
million, Katz's decisions are watched closely by industry.
The director's office decides how much of the budget will
be spent on grants and contracts coveted by companies.
And Katz has been available for outside
consultation: From 1993 through 2002, Katz took between $476,369
and $616,365 in fees from seven biotech and pharmaceutical
companies, according to his annual disclosure statements.
He consulted while chief of the dermatology branch at the
National Cancer Institute and continued after becoming arthritis
institute director in 1995.
Katz said that his private consulting broke
no rules and that he relied in part on Varmus' 1995 memo while
entering arrangements with companies.
"The consultations provided my global
knowledge as a dermatologist and research scientist,"
Katz said in written responses to questions from The Times.
"I have always received official permission to perform
these consultations and have performed these consultations
outside of my normal NIH work schedule and according to strict
government guidelines and rules."
One of his clients was Advanced Tissue
Sciences Inc.
The struggling biotech company in San Diego
hired Katz as a consultant in 1997, a year after he had announced
a new NIH research initiative for bone and connective-tissue
repair.
Advanced Tissue installed Katz on its scientific
advisory board and paid him fees between $142,500 and $212,500
from 1997 through 2002, according to his income-disclosure
reports.
During that time, Katz's institute pledged
$1.7 million in small-business research grants to the company.
The company announced nearly every grant in a news release;
Advanced Tissue's president termed the grants "an endorsement
by the government."
In his written response, Katz said that
he had signed a recusal "withdrawing myself from any
interactions between Advanced Tissue Sciences and the government
to remove any real or potential conflict of interest."
The grants were awarded following evaluations by NIH reviewers
outside of Katz's institute.
Responsibility for administering the grants
to Advanced Tissue was delegated to one of his subordinates,
Katz said.
The NIH policy manual says officials may
not take fees from companies seeking or receiving agency grants
"if the employee is working on or involved in these matters"
or "supervising others who work on these matters."
Katz said his subordinate "handled
all decisions regarding these grants without informing me."
However, Advanced Tissue kept him apprised
as NIH grants were obtained, a company executive said.
"He was informed," said Anthony
J. Ratcliffe, the firm's vice president for research until
its collapse a year ago. "We would have made a written
report to the SAB [scientific advisory board] members twice
a year. There would have been a report to the SAB meetings
on all grants, all grant activities."
Ratcliffe said the company dealt with Katz's
potential conflict of interest by paying him in fees alone,
and not stock options. Both men said Katz did not advise the
company on the NIH grants.
His consultations, Katz said, were limited
to his scientific expertise and "never involved, directly
or indirectly, the preparation or discussion of material which
could relate to any financial dealings between [Advanced Tissue]
and the NIH."
Kirschstein, the senior NIH official who
each year approved Katz's consulting with Advanced Tissue,
said she did not learn the company held grants with the arthritis
institute until The Times inquired.
"I didn't even know there were grants,"
Kirschstein said.
As it turned out, the grants would be among
the few positive financial developments for Advanced Tissue.
By December 2001, its cumulative net operating
losses were approximately $292.7 million. Barely a year later,
the company entered bankruptcy and shut its doors, having
collected about $1.5 million of the $1.7 million in small-business
research grants.
Life-and-Death Decisions
While Katz was consulting for Advanced Tissue, he also was
on the payroll of Schering AG, which made Fludara, a drug
that his research staff was using as an experimental treatment
for autoimmune diseases.
From the time he began consulting for Schering
AG in 1996 through 2002, Katz collected between $170,000 and
$240,000 in fees from the company, his disclosure reports
show.
In his responses to questions, Katz said
that he "first became aware" that Fludara was a
Schering AG product when The Times made inquiries.
Fludara had been approved by the Food and
Drug Administration in 1991 to treat leukemia, but the company
wanted to expand its use to other diseases, a goal the NIH
studies could advance.
Two people died in the studies conducted
by Katz's institute.
In one study using Fludara to treat muscular
disorders, a patient suffered what agency researchers reported
in July 1998 as a "sudden death … not thought to
be drug related."
The second fatality, indisputably, resulted
from the treatment. It involved "Subject No. 4,"
who had enrolled in a separate study, designed to treat kidney
inflammation related to lupus, a disease of the immune system.
Schering AG provided Katz's institute with
a supply of Fludara and with analyses of patients' blood samples
through its U.S. affiliate, Berlex Laboratories, records and
interviews show. The company also contributed a total of $60,000
to the institute to support the research, eliciting a July
1, 1998, thank-you letter from Katz.
Participants entering the study were warned
of some risks. The NIH advised them that Fludara might cause
damage to their blood cells and that, as a result, "blood
transfusions may be required."
That is what befell Jamie Ann Jackson,
identified in NIH documents as "Subject No. 4."
Jackson, a registered nurse, lived with
her husband, their two daughters and a son in Plainville,
Mass., about 37 miles southwest of Boston. She received four
transfusions between March and May of 1999, yet grew sicker.
On June 1, trembling with chills, Jackson
was admitted to the NIH Clinical Center in Bethesda. Within
days, lab results confirmed that she was in the grip of graft-versus-host
disease. The graft of outside material — in this instance,
blood from a transfusion — attacks and overwhelms the
immune system and organs of the new host.
Fatal in about 90% of cases, the malady
had been documented in leukemia and other cancer patients
who took Fludara. For that reason, the risk of graft-versus-host
disease was noted in the product labeling — as was a
warning about irradiating transfusions as a prevention.
But the NIH doctors did not specify that
transfusions should be irradiated for patients in the lupus
study. In an interview, Dr. John H. Klippel, then the institute's
clinical director, said he could not recall whether he or
his colleagues took stock of the label warning.
In Britain, authorities were more cautious,
recommending that blood transfusions for all patients taking
Fludara be irradiated. The British recommendations were described
in 1996 in The Lancet, a medical journal with an
international circulation.
Two weeks after being admitted to the NIH
Clinical Center, 42-year-old Jamie Ann Jackson died.
"Steve Katz was notified almost immediately,"
Klippel said.
Katz's subordinates warned the remaining
patients and their personal doctors about the death and, for
the first time, advised them to irradiate any transfusions.
The FDA was informed.
But the NIH office responsible for conducting
an inquiry into research deaths was not promptly notified.
And while Katz's institute stopped enrolling
recruits, the treatment of those already in the study continued
for nine months after Jackson's death.
After five of the other 12 patients given
Fludara experienced abnormal changes in their blood, increasing
their risk of infection, the experiment was stopped, 20 months
before its scheduled conclusion.
'Absolutely No Role'
While Fludara's use for anything other than leukemia remained
experimental, an increasing number of doctors were prescribing
it "off-label" for diseases of the immune system,
including rheumatoid arthritis.
Yet the NIH was slow in warning them about
the lethal, but preventable, problem of graft-versus-host
disease.
It was not until October 2000, 16 months
after Jackson died, that doctors from the NIH briefly summarized
the death in Transfusion, the journal of the American Assn.
of Blood Banks.
Meanwhile, three articles written by NIH
doctors and published from March 2000 through May 2001 referred
to the agency's work with Fludara without mentioning the risk
of graft-versus-host disease or the death in their study.
In an article published in the May 2001
issue of the journal Pharmacotherapy, the doctors, three from
Katz's institute, wrote that Fludara "was well tolerated"
and thanked the company for providing the drug and "analytical
support."
Not until last week — 4 1/2 years
after the event — did the same doctors appear as authors
of a full-length article describing Jackson's death. It was
published in Transfusion.
In his responses to The Times,
Katz said that, to his knowledge, "all matters concerning
the adverse event were handled according to standard operating
procedures."
Katz said that he had signed a recusal,
pledging not to participate in matters involving Schering
AG. He said he had nothing to do with initiating the study,
"was not advised that it was ongoing and had absolutely
no role in overseeing its conduct."
The Times documented three instances
in which he discussed the study: The July 1998 letter acknowledging
the company's first half of the $60,000 donation; the June
1999 phone call from Klippel notifying him of the death; and
a meeting in April 2000 with Kirschstein to discuss the fatality
and his institute's response to it.
Katz confirmed all three incidents in a
series of e-mail exchanges.
He said he wrote the letter without realizing
that Berlex Laboratories was the American arm of Schering
AG.
"At that time, I was unaware of any
relationship between Berlex Laboratories and Schering AG and
was, therefore, unaware that my sending the thank you letter
might present any conflict of interest."
Katz declined to identify when he learned
that Berlex was the U.S. affiliate of Schering AG.
The relationship between Schering AG and
Berlex has not been a secret. News articles describe Berlex
as Schering AG's U.S. business unit. The Berlex and Schering
AG Web sites make clear the affiliation. In 1998 — two
years after Katz was hired — Berlex accounted for 17%
of Schering AG's net global sales.
Oliver Renner, a spokesman in Berlin for
Schering AG, said: "Berlex Laboratories is a fully owned
subsidiary of Schering AG. We are distributing our products
under the name of Berlex in the United States. We also conduct
research and development work through our Berlex entities."
Katz, asked about the phone call he received
when Jackson died, said he did not then realize what company
made the study drug. Although the study was ongoing, he said
he did nothing in response to being notified of the death.
"No further action was required or
undertaken by me," Katz said.
He said he remained uninformed about Schering
AG's connection to the study when he met with Kirschstein
in April 2000.
"The reason that I did not exclude
myself from any contact regarding the lupus [clinical] trial
was that I was unaware, and no one on the staff brought to
my attention, that the trial had any relationship to Schering
AG," Katz said. He noted that the arthritis institute
first used Fludara for lupus in 1993, before he arrived as
director.
Representatives of Schering AG said the
company did nothing out of the ordinary in collaborating with
the NIH — and in hiring Katz.
"The discovery and development of
new pharmaceuticals often involves a combination of government
and private industry efforts," the company said in a
statement. "It is also a common practice for pharmaceutical
companies to work with many leading external experts….
In keeping with this practice, we have a consulting agreement
with a Dr. Stephen Katz from the NIH involving his expertise
in the field of dermatology."
Schering AG is no longer pursuing development
of Fludara as a treatment for autoimmune diseases.
Kirschstein, the NIH official who approved
Katz's consulting for Schering AG, said she had not known
its drug was being tested by his institute.
Kirschstein said she did recall being visited
by Katz and his top aide in April 2000. The NIH's human protection
office had just opened an internal review of the lupus-related
study, questioning the researchers' failure to protect against
graft-versus-host disease, as well as their failure to report
the death to agency investigators in a timely fashion.
"Dr. Katz and his scientific director
came to me … to tell me about a study in which a drug
was used and there was a death," Kirschstein said. "They
did not tell me the name of the drug, and did not tell me
much about the study, but told me that they and the [department]
were looking into it."
In a follow-up letter two years later,
the internal review absolved the institute of responsibility
for Jackson's death. Her husband has filed a wrongful-death
lawsuit against the government in U.S. District Court. The
lawsuit does not refer to Katz.
Jackson's mother, Carmella Tarte, said
time had not eased her grief.
"We all went to the hospital, but
we never even got to talk to her," Tarte said in an interview.
"It's been four years and, well, Thanksgiving was just
another day, you know? She has children she didn't see graduate."
About This Report
In late 1998, the Los Angeles Times began examining
payments from drug companies to employees of the National
Institutes of Health and the agency's research collaborations
with industry. This report is based on records from the federal
government and from companies, as well as scores of interviews.
In early 1999, the newspaper first sought
income-disclosure reports for all eligible employees of the
27 research institutes and centers of the NIH. The newspaper,
as of this month, had filed 36 requests with the NIH for documents
under the Freedom of Information Act.
According to NIH staff, the agency has
provided documents totaling 13,784 pages, including annual
financial-disclosure reports, memos and internal e-mails.
A significant number of NIH employees had
by this year stopped filing yearly income reports that are
open to public inspection. To assess the relative extent of
public financial disclosure at the NIH, The Times
in July queried dozens of other federal agencies under the
Freedom of Information Act.
Other documentation, describing products
and hundreds of research collaborations between the NIH and
industry, was retrieved from company and NIH Web sites, from
filings with the Securities and Exchange Commission, and from
lawsuits filed in federal and state courts. Other related
documents were obtained from the Food and Drug Administration
under the Freedom of Information Act.
Contributors
Times researcher Janet Lundblad in Los Angeles assisted in
this report. Researchers Robert Patrick and Christopher Chandler
in Washington also contributed.
Back to top
Liver
Transplant Thwarted by Blackout Succeeds on 2nd Try
By Denise Grady
Source: NY Times
Since the middle of August, every time
the telephone rang, Delyla Torres hoped it would be Mount
Sinai Hospital, calling to tell her a liver was on the way
and it was time for her transplant.
On Wednesday the call finally came. Ms.
Torres, whose transplant was canceled at the last minute when
the power failed on Aug. 14, got a new liver.
Her surgeon, Dr. Sasan Roayaie, said the
operation took about six hours and went well. He expected
Ms. Torres, 49, to make a good recovery. The liver she received
had been removed that morning from a patient who died in Buffalo.
In a telephone interview on Wednesday shortly
before the surgery, Ms. Torres said she felt elated but also
nervous as she waited in a hospital room with her son, 21,
and her daughter, 31. "It's hard to believe I'm here,"
she said. "But it's scary. I'm praying."
Last night, Ms. Torres began experiencing
some difficulties breathing, and doctors shifted her condition
to guarded from stable, said Mel Granik, a hospital spokesman.
Ms. Torres had cirrhosis and liver cancer,
caused by hepatitis C. As she waited, for weeks and then months,
for another liver, she grew more anxious and her health declined.
She thought about death. A transplant was her only hope, but
she feared the cancer would spread before an organ became
available, making her ineligible for the operation. She underwent
treatments in which doctors tried to contain the tumor by
heating it and choking off its blood supply.
She had first been put on the transplant
waiting list last May. A liver, also from a deceased patient
in Buffalo, became available on Aug. 14.
That afternoon, as Ms. Torres lay on a
gurney waiting to be wheeled into the operating room at Mount
Sinai, the lights went out, in what became the largest blackout
in North America. Though the hospital had its own generator,
Dr. Roayaie (pronounced roy-EYE) decided it was not safe to
begin such a long, complicated operation on backup power.
With little time to spare, since a liver is good for only
16 hours once it is removed from a donor, the organ meant
for Ms. Torres was sent on to Pittsburgh, the nearest transplant
center with full power and a patient who had the right blood
type, B. The patient was Clifton Birr, 52, a Vietnam veteran
who also had hepatitis C and cirrhosis.
Ms. Torres's name went back on the regional
waiting list — but she lost her first-place slot. Patients
sicker than she was, people facing death from liver failure,
had moved ahead of her. Livers are in short supply, and patients
with the most urgent need get transplants first. Nationwide,
17,266 people are waiting for transplants, and only 3,777
have received them so far this year. Hepatitis C, caused by
a blood-borne virus, is the leading reason for liver transplants
in the United States.
Dr. Roayaie said: "I wouldn't have
thought she would have to wait for so long. The list is so
unpredictable."
Despite the delay, he said, the outlook
for Ms. Torres is good, though, like virtually all recipients
who have had hepatitis C, she is at risk that the virus will
infect her new liver.
Mr. Birr, who said it had troubled him that his good fortune
had come at someone else's expense, was delighted to hear
that Ms. Torres finally got her transplant.
Back to top
Access To
Clean Needles - A Health Issue
Source: PressofAtlanticCity.com
The shame of it is that it seemed as though
there was a real chance this time.
But once again, New Jersey has missed an
opportunity to pass legislation that the scientific and medical
communities, backed by volumes of research, insist would save
lives.
A bill that would have legalized the possession
and over-the-counter sale of hypodermic needles and syringes
was pulled from consideration last week in the Senate Commerce
Committee.
Proponents say they will address criticisms
by the state Attorney General's Office and reintroduce the
bill in the next legislative session. But in the meantime,
those caught in the sickness of drug addiction will continue
to share whatever needles are available - and the HIV, Hepatitis
C and other deadly infections they carry.
New Jersey now has a governor who supports
the general idea of access to clean needles. Former opponents
of the concept, including Sen. William Gormley, R-Atlantic,
supported the bill. The legislation itself avoided the divisive
issue of needle-exchange programs and was crafted so that
it would not cost the state anything.
But New Jersey remains one of the last
states that still refuses to admit that this is a health issue,
not a debate on the evils of drug use.
The argument against access to needles
has an element of common sense: Illegal drug use is bad, and
supplying needles to addicts condones drug use. The Republican
legislative team from Ocean County tried to frame the issue
as part of the war against drugs and cited a Vancouver study
that claims there is no evidence that needle programs are
effective.
But the moral high ground crumbles under
the weight of research that has convinced the Centers for
Disease Control, the American Medical Association, the National
Academy of Sciences and the state Health Department that the
availability of clean needles does not create drug addicts.
But more importantly, the research shows
that access to clean needles slows the spread of AIDS and
other diseases, saving money spent on health care in the process.
Nationally, 25 percent of HIV infections are related to shared
needles. In New Jersey, the rate is 46 percent.
Those statistics translate to real people.
They may be drug addicts, but we should not turn our backs
on people who need the protection that this type of legislation
can easily provide.
Needle-access proponents promise to push
their bill again. They are confident they can address the
Attorney General's Office's concerns, which include the proper
disposal of needles, preventing clean needles from being sold
in illicit markets and providing literature about drug counseling
and treatment.
Legislators should do whatever it takes
to get some sort of program in place. More stalling in this
case will only cost more lives.
Back to top
December 09, 2003
Micrologix
licenses Hepatitis B Compound to Spring Bank Technologies:
US$2.6 Million NIH Grant Funding Approved for Development
VANCOUVER, BC, and MILFORD, MA, PRNewswire-FirstCall/ -- Micrologix
Biotech Inc., a developer of anti-infective drugs (TSX: MBI;
OTC: MGIXF), has completed a license agreement with Spring
Bank Technologies, Inc. (Spring Bank) of Milford, MA, under
which Spring Bank acquired exclusive worldwide rights to MBI-1313,
a nucleotide analogue under development as a treatment of
Hepatitis B Virus (HBV) chronic infections. As part of the
development agreement, Spring Bank has received a US$2.6 million
grant from the National Institutes of Health (NIH) to advance
development of the compound.
Under the terms of the agreement, Micrologix will receive
up to US$3.5 million in milestone payments during development
of the compound, collect royalties upon commercialization,
and obtain an equity position in Spring Bank. Spring Bank
will take over and fund all development of MBI-1313 and assume
responsibility for patent prosecution. Further terms of the
agreement were not disclosed.
Last year, Micrologix acquired the rights to a portfolio of
over 1,200 analogues for HBV and Hepatitis C Virus (HCV),
including MBI-1313 for HBV, as part of the asset acquisition
of Origenix, a Quebec-based biotechnology company focused
on the development of antiviral drugs.
Jim DeMesa, M.D., President & CEO of Micrologix stated,
"This agreement represents another example of our commitment
to leverage our broad intellectual property portfolio through
selected early stage alliances to help augment future value
creation, while allowing us to more effectively develop other
assets in our pipeline. This agreement, combined with our
other hepatitis programs, validates our acquisition of the
Origenix anti-viral portfolio and underscores the value of
the assets we acquired. Ultimately, our intent would be to
have multiple such out-license arrangements, thereby maximizing
our chances for several commercial opportunities."
"We are pleased to complete this license agreement with
Micrologix for MBI-1313 for the treatment of chronic Hepatitis
B infection", said Kris Iyer, Chief Scientific Officer,
Spring Bank Technologies. "Chronic Hepatitis B infection
is a major global health problem that will require novel therapeutic
approaches. We are excited to be working in collaboration
with the NIH, and are gratified by their continued support
for the development of this novel molecule. The $2.6 million
NIH grant awarded Spring Bank will fund ongoing preclinical
development leading to IND submission, with additional potential
future funding for early clinical studies."
About MBI-1313
MBI-1313 is a -nucleotide analog originally discovered by
Dr. Iyer and developed in collaboration with the NIH, Georgetown
University (Dr. Brent Korba) and Utah State University (Dr.
John Morrey). The molecule has shown high potency against
HBV in in vitro assays and has demonstrated efficacy in an
established animal model of HBV infection.
Background on Hepatitis B (HBV)
There are approximately 350 million people worldwide with
chronic hepatitis B virus infection, of whom approximately
33% have potentially progressive and life-threatening liver
disease associated with their chronic HBV infection. Chronic
hepatitis B can lead to cirrhosis, liver failure and liver
cancer. Globally, hepatitis B accounts for over one million
deaths annually, making it the ninth leading cause of death
worldwide
About Spring Bank
Spring Bank, a privately held biotechnology company based
in Milford, Massachusetts, is focused on the discovery and
development of novel drugs for the treatment of infectious
disease. Dr. R. P. Iyer, Vice President and Chief Scientific
Officer has published 90 papers in nucleic acids chemistry
and small molecule chemistry and is an inventor in 30 issued
and filed patents. He has been involved in the discovery and
development of a number of compounds against infectious diseases
and other therapeutic areas.
About Micrologix
Micrologix Biotech Inc. is engaged in the research, development,
and commercialization of drugs that advance therapy, improve
health, and enrich lives. The Company's focus is toward anti-infective
drug development with three product candidates in human clinical
development, multiple product opportunities in preclinical
development, and several early-stage technologies in various
stages of research and evaluation.
Certain statements in this news release constitute "forward-looking
statements" within the meaning of the Private Securities
Litigation Reform Act of 1995, which involve known and unknown
risks, uncertainties and other factors that may cause our
actual results to be materially different from any future
results, performance or achievements expressed or implied
by such statements. Forward-looking statements in this release
include, but are not limited to, Micrologix receiving up to
US$3.5 million in milestone payments during development of
the compound, collecting royalties upon commercialization.
These statements are only predictions and actual events or
results may differ materially. Factors that could cause such
actual events or results expressed or implied by such forward-looking
statements to differ materially from any future results expressed
or implied by such statements include, but are not limited
to: early stage of development; technology and product development;
dependence on and management of current and future corporate
collaborations; future capital needs; uncertainty of additional
funding; no assurance of market acceptance; dependence on
proprietary technology and uncertainty of patent protection;
intense competition; manufacturing and market uncertainties;
and government regulation. These and other factors are described
in detail in the Company's Annual Information Form and Annual
Report on Form 20-F, forthcoming news releases and other filings
with the Canadian securities regulatory authorities and the
U.S. Securities & Exchange Commission. Forward-looking
statements are based on our current expectations and Micrologix
is not obligated to update such information to reflect later
events or developments.
The Toronto Stock Exchange has not reviewed and does not accept
responsibility for the adequacy or accuracy of this release.
Source: Micrologix Biotech Inc.
CONTACT: Investor & Media Relations Contacts: Jonathan
Burke, Micrologix
Biotech Inc., Telephone: (604) 221-9666 Extension 241, Toll
Free:
1-800-665-1968, Email: jburke@mbiotech.com;
Shayne Payne or Dian Griesel,
Ph.D, The Investor Relations Group, Telephone: (212) 825-3210,
Email:
theproteam@aol.com;
Doug Jensen, Spring Bank Technologies, Telephone:
(334) 382-4347, Email: djensen@springbank.us;
To request a free copy of this organization's annual report,
please go to
http://www.newswire.ca/
and click on reports@cnw.
Back to top
December 9th, 2003
Organetix,
Inc. Announces Positive Test Results for Hepatitis C Treatment
NEW YORK--(BUSINESS WIRE)--12/09/2003--Organetix,
Inc.(www.organetixinc.com)
(OTCBB:OGTX) announced that previous testing of Organetix'
A4+L has demonstrated positive results in treating patients
suffering from Hepatitis C.
Dr. Jose Cabanillas along with two independent
doctors, Joseph Nystrom, M.D. from Florida and Dr. Hugo Marquez
S. from Lima conducted the tests on Hepatitis C patients from
Canada. The following was their conclusion:
"Most importantly, all patients reported
dramatic improvement in symptomatology. We expect further
prospective study and follow-up to demonstrate continued improvement
in all parameters."
Dr. Cabanillas' research is based on the
success of treating numerous individuals with Hepatitis C
for more than a decade. Testimonials of patient success stories
using the liver product to treat Hepatitis C have been documented
in the Canadian media. Various stories have been documented
by the Vancouver Sun, The Province (also a Vancouver newspaper)
and the Canadian Broadcasting Corporation (CBC) - Radio Division
in Canada.
CBC Radio in Canada released an investigative
story on Hepatitis C patients treated with the liver product
in October 2002. The story received the Dan McArthur Award
for investigative journalism by the Radio and Television News
Directors Association in May of 2003.
Research indicates that A4+L appears to
be regenerating liver tissue which allows the liver to begin
functioning again despite years of damage from the virus.
As a result, this liver product may be useful for all liver
disorders. Studies have indicated that A4+L is capable of
eliminating most of the symptoms associated with Hepatitis
C quickly and effectively, without any known side effects.
By contrast, current therapies for Hepatitis C can typically
cause serious side effects for its users.
To date, there are three major companies
that share the existing multi-billion dollar Hepatitis C market:
Schering-Plough, Genta, and Roche. Worldwide drug sales for
Hepatitis C rose from $900 Million in 1998 to several Billion
less than two years later. It is estimated that the market
for such drugs may exceed $6 Billion by 2004.
Dr. Cabanillas, a Medical Advisor to Organetix, has been a
speaker at conferences and seminars and has several credited
publications in relevant journals. He recently lectured to
Cornell University's pre-med students at their bio-diversity
laboratory in Punta Cana, Dominican Republic.
About Organetix, Inc.
Organetix, Inc. is a biotechnology company
that is in the process of treating patients with a unique
nutraceutical that appears to relieve symptoms of Hepatitis
C without any known side effects. Organetix has the exclusive
worldwide rights for this liver product. Hepatitis C is a
life-threatening, blood-borne, liver disease that is caused
by a virus. It is estimated that millions of individuals worldwide
are infected with Hepatitis C making it one of the greatest
public health threats faced in recent years.
Statements contained in this press release,
which are not historical facts, are forward-looking statements
as that term is defined in the Private Securities Litigation
Reform Act of 1995. These forward-looking statements are based
largely on the Company's expectations and are subject to a
number of risks and uncertainties beyond the Company's control,
including but not limited to economic, competitive and other
factors affecting the Company's operations, management team
effectiveness, expansion strategies, available financing,
market prices and recovery costs, government regulations involving
the Company, facts and events not known at the time of this
release, and other factors discussed in the Company's filings
with the Securities and Exchange Commission.
These statements are not guarantees of future performance
and readers are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date
of this release. The Company undertakes no obligation to update
publicly any forward-looking statements.
CONTACT:J.R. Axelrod & Company 516-791-0000
ext. 102.
SOURCE: Organetix, Inc.
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December 10th, 2003
Insulin
Resistance, Chronic Hepatitis C and Fibrosis Progression
Source: www.gastrohep.com
Hepatitis C virus may induce insulin resistance
irrespective of the severity of liver disease, find researchers
in the December issue of Gastroenterology.
Chronic hepatitis C virus infection is
associated with an increased prevalence of type 2 diabetes.
In this study, researchers from Australia
assessed whether virus-induced insulin resistance was a mechanism
for fibrogenesis in chronic hepatitis C virus infection.
The team evaluated 250 hepatitis C virus-infected subjects.
They examined the relationship between
histological findings, and anthropometric and biochemical
data, including insulin resistance. Insulin resistance was
determined by the homeostasis model assessment (HOMA-IR).
The team also compared fasting serum insulin,
C peptide, and HOMA-IR levels in 121 hepatitis C virus patients
with stage 0 or 1 hepatic fibrosis and 137 healthy volunteers.
Insulin resistance was an independent predictor
of the degree of fibrosis.
The researchers found that hepatitis C
virus-infected subjects with stage 0 or 1 hepatic fibrosis
had higher levels of insulin, C peptide, and HOMA-IR than
the controls.
In the 250 hepatitis C virus patients,
viral genotype and portal inflammation were univariate predictors
of HOMA-IR.
Using multiple linear regression analysis,
the team identified BMI, previous failed antiviral treatment,
portal inflammatory grade, and genotype 3 status as independent
predictors of HOMA-IR. Patients with genotype 3 had significantly
lower HOMA-IR than other genotypes. The team also found that
HOMA-IR was an independent predictor for the degree of fibrosis,
as well as the rate of fibrosis progression.
Dr Jason Hui’s team concluded, “Hepatitis
C virus may induce insulin resistance irrespective of the
severity of liver disease, and this effect seems to be genotype
specific”.
“Further, our findings support the hypothesis that insulin
resistance may contribute to fibrotic progression in chronic
hepatitis C virus infection”.
Gastroenterol 2003; 125(6): 1695-1704
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Judge Rules
for HIV Patient in Transplant
Source: The Associated Press
PITTSBURGH (AP) -- An HIV-positive man in need of a liver
transplant was wrongly denied coverage under the state's Medicaid
program, an administrative law judge ruled.
William Jean Gough's liver is deteriorating
because of hepatitis C. The 46-year-old was accepted as a
strong candidate for the lifesaving operation in August by
Pittsburgh's Thomas E. Starzl Transplant Institute.
The state Department of Public Welfare,
which oversees the state's Medicaid program, denied coverage
for Gough, saying that infection with the AIDS virus is a
life-limiting condition that rules out a transplant.
In a ruling made public Wednesday, Judge
Bernadene Kennedy dismissed the state's argument, saying that
scientific advances allow people with HIV to live full lives.
Gough “could live 10, 20, 30 years
or more with a liver transplant,” Kennedy wrote. “Given
his ability to successfully control his HIV, the appellant
may live a prolonged life and maintain quality of life equivalent
to non-HIV transplant patients.”
The judge expedited the case because Gough's
condition worsens by the day and he could be ineligible for
a transplant if his liver deteriorates too much.
Doctors said the Altoona man could die
in nine to 12 months without a transplant. The average wait
is six to 12 months.
`”I've struggled with this disease
for many years and you've got to have hope,” Gough said
Wednesday. “I just think it's a lack of education in
our health care system. It seems to me the state's working
off of old criteria.”
The Department of Public Welfare will not
appeal the judge's ruling, spokeswoman Stephanie Suran said.
It is the second time in two months that
Lambda Legal, a gay legal rights group, has successfully argued
that patients with HIV should not be excluded from transplants
just because they are HIV-positive.
In October, Kaiser Permanente, one of the
nation's largest health maintenance organizations, approved
a kidney transplant for an HIV-positive man in Denver, reversing
an earlier decision. The HMO initially refused John Carl's
request for a new kidney, saying a transplant on someone with
the AIDS virus is too risky because drugs used to prevent
rejection of a new organ can jeopardize their already weakened
immune systems.
On the Net:
Lambda Legal: http://www.lambdalegal.org
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December 11th, 2003
Lamivudine
Controls Viral Replication in Relapsed Hepatitis B Patients
Although Resistance Eventually Develops
By Emma Hitt, PhD
Lamivudine can control viral replication
in HBeAg-negative chronic hepatitis B patients who have relapsed,
but viral resistance eventually develops, new research suggests.
Long-term use of lamivudine appears to
be safe in patients with HBeAg-negative chronic hepatitis
B, although the emergence of lamivudine-resistant hepatitis
B virus (HBV) mutants is a concern.
In a previous study, Grazia Niro, MD, with
the Hospital Casa Sollievo della Sofferenza IRCSS, San Giovanni
Rotondo, Italy, and colleagues demonstrated that combining
lamivudine with interferon could prevent the emergence of
lamivudine-resistant mutations. In that study, no patient
receiving combination therapy developed YMDD mutants during
therapy, whereas 19% of patients treated with lamivudine alone
experienced a virological breakthrough.
In the current study, the researchers evaluated
the benefits of long-term re-treatment with lamivudine monotherapy
in 36 HBeAg-negative chronic hepatitis B patients, 20 of whom
relapsed after a previous course of lamivudine monotherapy
and 16 who relapsed after combination therapy with lamivudine
plus interferon.
The researchers conducted biochemical and
virological tests every 3 months. They also sequenced the
region coding for the YMDD amino acid motif at baseline and
breakthrough.
The length of re-treatment averaged 24
months. The virological response peaked at 6 months (94.4%),
and declined to 66.7% and 50% at 12 and 24 months, respectively.
The rates of breakthrough were 2.9%, 31.4%, and 48.6% at 6,
12 and 24 months, respectively.
By the second year, 62.5% and 40% in the
lamivudine/interferon and lamivudine group, respectively were
considered responders (P = .10). The 18 responders at month
24 were on therapy after 25 to 51 months of treatment. The
researchers report that 14 maintained a response, 9 of them
from the lamivudine/interferon group and five from the lamivudine
group.
"For the first time, these results
establish the benefit of re-treatment with lamivudine monotherapy
for anti-HBe-positive patients," Dr. Niro and colleagues
note.
They conclude that re-treatment with lamivudine
can control viral replication, and the effect is maintained
for the initial 12 months in two-thirds of patients, but the
subsequent response declines due to the development of viral
resistance.
Aliment Pharmacol Ther 2003;18:933-940.
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December 12th, 2003
Hepatitis
C Virus-Positive Renal Donations Heighten Mortality Risk
Drug Week
According to published research from the
United States, "kidneys from donors who are positive
for hepatitis C virus (DHCV) have recently been identified
as an independent risk factor for mortality | 
