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Date: Thu Jan 3, 2002
4:40 am
Subject: Info: Hepatzyme: Saftey Analysis of Phase I Study
Heptazyme: safety analysis of phase I study
NATAP - www.natap.org
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Heptazyme: a new antiviral for treating HCV
AASLD conference, Dallas, Nov 2001
Reported for NATAP by Andrew Talal, MD, NY-Cornell
Hospital, NYCsee NATAP website for AASLD coverage
www.natap.org
Abstract #646. Safety analysis of a phase I study of
heptazyme, a nuclease resistant ribozyme targeting
hepatitis C (HCV) RNA
BKG/objectives: Ribozymes are catalytic RNA molecules
designed to cleave specific RNA sequences. Ribozymes
have been stabilized to resist enzymatic and chemical
degradation. Ribozyme cleavage of RNA in cells results
in a reduction of the RNA available for translation, a
reduction in viral protein synthesis, a reduction in
minus-strand RNA intermediate, and a reduction in
nascent plus strand RNA. The ultimate result would be
a decrease in progeny virions that can contribute to
viral load. Heptazyme, a particular form of ribozyme,
has been designed to cleave the HCV 5-UTR and can
inhibit virus replication in vitro in an HCV-polio
virus chimera. The goal of the current trial was to
evaluate the safety of Heptazyme in individuals with
chronic HCV infection.
Methods: Prospective, 28-day trial in patients
proscribed one of four doses of Heptazyme:
A- 3 mg
B- 10 mg
C- 30 mg
D- 90 mg
Results: 19/24 subjects reported a total of 39 adverse
events that were rated as possibly or probably related
to Heptazyme. Gastrointestinal side effects and
changes in emotional state were particularly common.
Conclusions: Heptazyme was safe and well-tolerated and
a phase II study using the medication in patients with
chronic hepatitis C has been arranged.
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Levothyroxine use
could increase number of transplantable donor organs
Last Updated: 2002-01-03 16:20:36 EST
(Reuters Health)
By Megan Rauscher
NEW YORK (Reuters Health) - Administering
thyroid hormone to brain-dead patients, who are potential organ donors,
could lead to a dramatic increase in the number and quality of organs for
transplantation, according to Dr. George C. Velmahos, of the University of
Southern California, Los Angeles.
As many as 25% of potential organ donors are lost due to
sudden physiologic deterioration after brain death, Dr. Velmahos and
colleagues note in Archives of Surgery for December 2001. "Even more organs
are lost as a consequence of the high dose of vasopressor required to
maintain adequate perfusion to the brain-dead organ donor," they write.
Diminished thyroxine (T4) levels are believed to be responsible for
hemodynamic instability after brain death.
"If we can sustain their organs for a longer period of
time by stabilizing their physiologic status through the administration of
T4, we increase dramatically the likelihood that other persons will be
saved," Dr. Velmahos told Reuters Health.
In a prospective study of 19 hemodynamically unstable
patients with traumatic or nontraumatic intracranial lesions who were
declared brain-dead, levothyroxine significantly decreased vasopressor
requirement and prevented cardiovascular collapse.
Dr. Velmahos said he was not surprised by the findings.
"With this study we just placed a scientific stamp to a protocol that we
have been practicing for the last 5 years," he said. Unfortunately, the
wider transplant community has not fully embraced the practice.
The clinical implications of thyroid hormone use in
brain-dead potential organ donors are "enormous," Dr. Velmahos said. "For
every brain-dead patient, another six to eight persons can stay alive after
organ donation," he said, through the harvesting of the heart, lungs, liver,
pancreas, and kidneys.
Arch Surg 2001;136:1377-1380.
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Second group announces 'knock
out' cloned pigs
By Merritt McKinney and Richard Woodman
NEW YORK, Jan 03 (Reuters Health) -
Scientists have cloned four "mini-pigs" that lack one copy of a gene that
triggers a hostile immune response in humans, bringing researchers a step
closer to transplanting organs from pigs to people, according to a report
published in the journal Science on Thursday.
The publication follows the announcement by a second group
of researchers on Wednesday that they have also produced similar cloned
piglets. Those results are not yet published in a scientific journal.
The cloned pigs lack one copy of the gene for a molecule
called alpha-1,3-galactosyltransferase (GGTA1). The molecule, normally found
on the surface of pig cells, has been a major obstacle for pig-to-human
transplants because it triggers a strong immune reaction in humans,
resulting in rejection of a transplanted organ.
Two of the piglets died shortly after birth, and another
died a few weeks later, but the four surviving piglets are healthy. The baby
pigs are from a strain of specially bred "miniature swine," but are even
smaller than other noncloned piglets of the same strain.
The animals appear healthy, although the investigators did
detect some abnormalities that do not appear to have a harmful effect on the
animals, including an eye defect and small ear flaps on one animal. They
also found heart defects in two animals, including one that died.
To be successful, scientists need to create pigs that lack
two copies of the gene for GGTA1. The researchers hope to obtain an animal
free of the molecule by breeding the cloned pigs.
Since the number of patients waiting for an organ
transplant greatly exceeds the available supply of human organs, one
potential solution has been to transplant organs from other species into
people. The pig is the leading candidate for transplants across the species
barrier, a technique known as xenotransplantation.
The study published in Science was conducted by a team of
researchers led by Dr. Randall S. Prather, of the University of Missouri in
Columbia. Several of the researchers are employees of Immerge
BioTherapeutics in Charlestown, Massachusetts, a joint venture company of
BioTransplant Incorporated and Novartis Pharma AG.
"This is going to have significant implications in the
field of xenotransplantation," Prather told Reuters Health in an interview.
The successful "knocking out" of the gene may also be
useful to agricultural researchers as well as scientists who study models of
human diseases in pigs, according to Prather. The Missouri researcher also
noted that cloned pigs are from a specially engineered line of pigs whose
tissues are unlikely to pass disease to people. The big concern with
xenotransplantation, Prather explained, is that endogenous retroviruses,
which are harmless in the donor species, will infect the recipient of a
transplant.
"In this line of pigs, that doesn't occur," he said.
"We have been actively developing a line of miniature
swine that offers many advantages as a potential donor for
xenotransplantation, including their organ size, which is appropriate for
human recipients," said Julia Greenstein, CEO and President of Immerge.
Robert Hawley, associate director of animal genetic
engineering at Immerge said, "Based on the success reported today, we can
now proceed with pig strains chosen solely for their advantages in
xenotransplantation rather than their large-scale availability.
"We believe this line of miniature swine offers the
greatest potential for clinical use in humans, and we are working closely
with the University of Missouri-Columbia and our commercial partner, Infigen
Inc, to develop these swine with this goal in mind."
On Wednesday, Scottish biotech firm PPL Therapeutics Plc.,
which helped create Dolly, the world's first cloned sheep, announced its
cloning techniques had resulted in the birth on Christmas Day of five
similar "knock-out" piglets.
A PPL spokesperson denied the firm's announcement before
publication in a scientific journal was designed to upstage Immerge
BioTherapeutics.
Ian Smith, biotechnology analyst at Lehman Brothers, said
that if xenotransplantation proved possible it would be a "massive step
forward in relieving the current shortage of suitable organs.
"But there are a number of serious issues, including the
possibility of introducing pathological viruses into humans. The risk from
viruses is an unanswered question--and it won't be answered until you have
had organs transplanted into humans over many years."
The British Union for the Abolition of Vivisection
criticized the research, saying it caused unacceptable suffering to animals.
"Not only do we question the right to genetically engineer animals to use as
spare-parts, we also believe that the science of xenotransplantation is so
poorly developed that clinical trials cannot reasonably be considered."
SOURCE: Sciencexpress 2002;10.1126.
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Thursday January 03 07:00
PM EST
Round Up
the Unusual Suspects
By Sharon Lerner
Village Voice Writer
After a businessman sick with smallpox arrived in New
York in 1947, infecting four people before dying himself, officials
sprang into action. The city vaccinated 6 million people in a month.
That contained the epidemic, but at a cost: Between four and eight
people died from reactions to the vaccine. In fact, with only three
people succumbing in the initial outbreak, the vaccine was ultimately
more deadly than the disease itself.
"It raises the classic public-health dilemma," says
David Rosner, professor of public health and history at Columbia
University. "Is a solution going to harm more people than it helps?"
In the wake of September 11, that dilemma is back with
a few new twists. Two weeks ago, the federal government released a
revised version of legislation the Bush administration hopes every state
will pass, which would solidify government authority to enforce
vaccination and isolate people exposed to infectious diseases. Though
the law does not distinguish among contagious diseases that could set
off the emergency powers, it seems designed to counter smallpox—the
deadly virus that bioweapons experts fear may have fallen into terrorist
hands.
But while the bill lays out an emergency strategy, in
which those exposed to a contagious disease are either inoculated or
quarantined, the smallpox vaccine now being stockpiled by the government
can endanger—and even kill—people with suppressed immune systems. Under
the proposed law, it's unclear how these people—including an estimated
900,000 Americans infected with HIV (news
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web sites) and more than 200,000 living with transplants, as well as
cancer patients and people with chronic diseases—will be treated in the
event of a true health emergency.
The Model State Emergency Health Powers Act, drafted
by the Centers for Disease Control and Georgetown health policy
professor Larry Gostin, would allow for forced isolation in the event of
a public health emergency. Health officials would also have the power to
seize hospitals and property (including cell phones, if they're jamming
circuits), identify infected individuals, ration medication, and mandate
testing, treatment, and vaccination. The act even allows health
officials to call in the militia if they see the need.
But beyond specifying that authorities are not allowed
to compel people to be vaccinated if it is "reasonably likely to lead to
serious harm," the law doesn't outline protections for the growing
number of immune-suppressed people who may be harmed by the vaccine.
Because of advances in treating people with cancer, AIDS (news
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web sites), and other serious diseases, "the number of [these
people] is much greater than at any other time," says Joel Kuritsky,
director of the National Immunization Program and Early Smallpox
Response and Planning at the CDC.
Some emergency planners have focused on
immune-suppressed people as threats to the general public during a
possible outbreak, both because they are more vulnerable to infection
and more likely to pass it on, since they emit more viral particles in
their breath. Peter Jahrling, senior scientist at the U.S. Army Medical
Research Insitute of Infectious Disease in Fort Detrick, Maryland, has
said that "having a lot of immune-compromised people during a smallpox
outbreak will be like pouring kerosene on the fire."
The situation can be even more frightening from
vulnerable people's perspective. In the event of a smallpox outbreak,
Kuritsky says, they and their doctors would have to decide "whether the
risk [posed by the vaccine] outweighed the benefit." A June 22 issue of
the CDC publication Morbidity and Mortality Weekly Report details
some of these risks, citing the deaths of two HIV-infected people who
participated in smallpox vaccine trials, as well as an HIV-positive
military recruit who developed severe vaccinia, a life-threatening
condition in which sores spread all over the body.
Because of the seriousness of these problems and their
frequency (roughly 5.2 in 1000 people vaccinated report side effects
ranging from rashes to encephalitis), health authorities say that even
in the event of a serious outbreak they would likely inoculate only a
few thousand people—those directly exposed to the virus and their
contacts. But what might happen if some of those exposed were immune
suppressed to begin with?
According to Gostin, who has also written extensively
about quarantine, isolation would be a "rare but necessary" last resort.
"If people were a risk to others, then they would be subject to
isolation," he says. If such people were unable to be vaccinated, "we
would provide care and treatment and a safe place. If they were exposed,
we would place them in isolation but make sure they were given due
process, food, and clothing."
But according to AIDS activists, this resurrection of
quarantine—a public-health relic that has fallen out of use with the
taming of infectious diseases like measles, scarlet fever, and
smallpox—raises serious concerns about civil liberties.
Many point to the past misuses of quarantine, which
has not been used on a wide scale in the U.S. for more than 80 years.
Before that, forced isolation was often applied unevenly. When a cholera
outbreak was reported on a ship in New York Harbor in 1892, the Port
Authority sequestered only poor immigrant passengers in unsanitary
conditions below deck—58 of whom died—while moneyed travelers were
allowed to go free. In San Francisco, the quarantine set off by a
bubonic-plague epidemic in 1900 applied only to Chinese businesses and
homes.
The modern-day quarantine laid out in the new law is
likely to be similarly abused, according to civil libertarians. "It's a
recipe for discriminatory application," says Donna Lieberman, executive
director of the New York Civil Liberties Union. Lieberman points to a
section of the law that grants the power to isolate and quarantine a
broad swath of "individuals or groups" who have not been vaccinated,
treated, or tested. "We are concerned that emergency powers will be used
to target minority groups, whether they be gays or people of color or
those perceived to be most at risk of infection."
Advocates contend the rounding up of certain groups,
were it to happen, would be doubly unfair. "This isn't a situation in
which people are unwilling to comply with a requirement," says Tanya
Ehrmann, director of public policy at AIDS Action in Washington, D.C.
"It's that the vaccine would kill us. What are we supposed to do?"
Perhaps the most cutting criticism of quarantine comes
from the author of the emergency health powers bill himself. "It is
probable that a population exposed to a biological weapon will have
dispersed well beyond any easily definable geographic boundaries before
the infection becomes manifest and any disease containment measures can
be initiated" is how Gostin and his colleagues summed up the dubious
effectiveness of quarantine against bioterrorism in a recent issue of
the Journal of the American Medical Association (news
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web sites).
Nevertheless, emergency health bills seem destined for
passage across the country. In New York, Richard Gottfried, chair of the
State Assembly's health committee, is planning to hold public-comment
sessions on the proposed legislation next month. Criticism of the bill
already has sparked revisions. A first version—which actually made it to
the Assembly floor in October—left open the possibility that existing
health problems such as AIDS and hepatitis could be considered medical
emergencies, giving states the authority to mandate testing and
reporting, regardless of existing law. Gottfried is confident that this
version of the bill will not pass and that a more measured one
ultimately will. Calling Gostin's draft "an excellent starting point,"
Gottfried maintains that it is necessary to update the state
public-health code, sections of which are more than 50 years old.
That law already gives health commissioners the power
to quarantine entire buildings and even whole towns. As recently as
1992, when drug-resistant tuberculosis was on the rise, the state health
commissioner invoked this power, routinely filling locked wards at
Bellevue with patients who were unwilling or unable to take their TB
medications. What's more, state law still includes a version of the
provision that allowed Typhoid Mary, a turn-of-the-century food preparer
who refused to wash her hands, to be exiled to an island near what is
now La Guardia Airport.
Given these already vast powers, some question the
necessity of the emergency bill. When asked whether he wanted more power
to deal with the anthrax threat and other unprecedented health concerns
that have come up since September 11, Wilfredo Lopez, general counsel of
the city health department, replied, "No. The health authorities have
always had the authority to isolate and quarantine. We don't need new
legislation to provide that authority."
George Annas, chair of the health law department at
the Boston University School of Public Health, agrees. Annas says
September 11 should have convinced lawmakers that health care workers
and patients need not be forced to act in the public's interest. "Now we
know how people react, and they react really well on their own," says
Annas. "In a bioterrorism event, the American public is not the enemy."
Yet, as with the federal anti-terrorism legislation
drafted since the country entered its security panic, the Emergency
Health Powers Act is harnessing legitimate fears to fuel restrictive
measures. Ultimately this reflex can backfire, according to Catherine
Hanssens, staff attorney of the Lambda Legal Defense and Education Fund.
"The only way for a public-health system to work is through the trust of
the public," she warns. "You need people to feel safe accessing medical
facilities where infectious diseases will be detected. You can't just
lock everybody up."
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Wednesday January 02
02:55 PM EST
Man
who came out on public TV dies at 50
By Gay.com / PlanetOut.com Network
SUMMARY: Lance Loud, who received national
attention by coming out on a 1973 television documentary series, died
Saturday in Los Angeles at the age of 50.
Lance Loud, who received national attention by coming
out on a 1973 television documentary series, died Saturday in Los
Angeles at the age of 50.
He died from complications of hepatitis C, according
to his sister Delilah.
Loud and his family were the subject of "An American
Family," a PBS series that prefigured the "reality shows" of today. Shot
over seven months in 1971, the show aired in 1973 and became popular as
a real-life soap opera.
"In 1970, television ate my family," Loud wrote years
later. "The Andy Warhol prophecy of 15 minutes of fame for any and
everyone blew up on our doorstep."
While many praised Loud's courage to be openly gay on
the show, others criticized Loud and his family members for
participating in "the most expensive home movie in history," according
to the Washington Post.
As a freelance journalist, Loud wrote for the
Advocate, Details and Interview, among other publications. He also was
an actor and a former musician with a band called the Mumps.
He is survived by his parents and siblings.
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Lilly and Vertex
Pharmaceuticals Select Novel Oral Anti-Hepatitis C Compound - First
Announcement of Hepatitis C Protease Inhibitor Designated as Development
Candidate
INDIANAPOLIS, Ind. and CAMBRIDGE, Mass., Jan. 7 /PRNewswire/ -- Eli Lilly
and Company (NYSE: LLY - news) and Vertex Pharmaceuticals Incorporated (Nasdaq:
VRTX - news) announced today that they have selected LY570310 (VX-950), a
novel small molecule protease inhibitor for the potential treatment of
hepatitis C virus (HCV) infection, as a development candidate. The compound
is the first drug development candidate of a new class of antiviral drugs
being studied to inhibit hepatitis C NS3-4A protease, an enzyme considered
essential for HCV viral replication. Preclinical studies of LY570310 are now
underway in preparation for the expected commencement of Phase I clinical
trials in early 2003. Under the terms of the collaboration agreement, Vertex
has received a $5 million milestone payment from Lilly in connection with
the selection of this development candidate.
(Photo: http://www.newscom.com/cgi-bin/prnh/20000119/VERTEXLOGO ) ``HCV
protease has proved to be a challenging target for drug discovery, but
Vertex and Lilly have successfully identified a potent, oral inhibitor
suitable for development,'' said John Thomson, Ph.D., Vice President of
Research for Vertex. ``The flat active site of the enzyme and the difficulty
of achieving viral replication in the laboratory presented substantial
initial hurdles for our chemists and biologists. Through the design of novel
chemical scaffolds and development of proprietary surrogate assays, Lilly
and Vertex scientists have pioneered the design of the first HCV protease
inhibitor drug candidate. Indeed, LY570310 represents a major achievement
for the Vertex and Lilly team.''
``We are excited that hard work on the part of Lilly and Vertex
scientists has yielded a promising drug development candidate with potential
to treat HCV,'' said Gail Cassell, Ph.D., Vice President of Infectious
Disease Research for Lilly. ``HCV infection is recognized as a major threat
to public health. A drug that directly blocks HCV viral protease has the
potential to be a potent new option for the treatment of chronically
infected patients.''
Chronic hepatitis C infection afflicts approximately 2.7 million people
in the U.S., many of whom are unaware of the infection, which is often
undetected for up to 20 years following initial infection. Worldwide, the
disease strikes as many as 185 million people. HCV causes inflammation of
the liver, which may lead to fibrosis and cirrhosis, liver cancer, and
ultimately, liver failure. Each year, 8,000 to 10,000 people in the U.S. die
from complications of HCV. Current treatments have been effective for only
40 to 60 percent of chronically infected HCV patients and are associated
with significant side effects.
``Therapeutics that directly inhibit viral assembly paved the way for
important treatment advances for patients infected with HIV,'' said Vicki
Sato, Ph.D., President of Vertex. ``While our HCV protease inhibitor has not
yet been tested in patients, we are optimistic that drugs such as LY570310
could usher in a similarly significant treatment advance for patients with
HCV.''
Vertex Pharmaceuticals Incorporated is a global biotechnology company.
Vertex seeks to discover, develop and commercialize major pharmaceutical
products independently and with partners. Chemogenomics, Vertex's
proprietary, systematic, genomics-based platform, is designed to accelerate
the discovery of new drugs and to expand intellectual property coverage of
drug candidate compounds and classes of related compounds. Vertex's first
approved drug is an HIV protease inhibitor. Vertex has more than 10 drug
candidates in clinical and preclinical development to treat viral diseases,
inflammation, cancer, autoimmune diseases and neurological disorders.
Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of best-in-class pharmaceutical products by applying the latest
research from its own worldwide laboratories and from collaborations with
eminent scientific organizations. Headquartered in Indianapolis, IN, Lilly
provides answers -- through medicines and information -- for some of the
world's most urgent medical needs. Additional information about Lilly is
available at www.lilly.com.
This press release may contain ``forward-looking'' statements, including
statements that Lilly and Vertex anticipate initiating clinical studies with
LY570310 (VX-950) in early 2003, and that HCV protease inhibitors could
provide a major clinical advance in treatment of HCV. While Lilly's and
Vertex's management use their best efforts to be accurate in making forward-
looking statements, those statements are subject to risks and uncertainties
that could cause actual results to vary materially. Those risks and
uncertainties include, among other things, that preclinical studies may not
lead to the initiation of Phase I clinical trials, that clinical trials may
not result in a marketable product and that Lilly and Vertex may be unable
to secure regulatory approval of, or successfully market, a drug candidate.
For further discussion of these and other risks and uncertainties, see
Lilly's and Vertex's filings with the United States Securities and Exchange
Commission. Both Lilly and Vertex disclaim any intention or obligation to
update or revise any forward-looking statements, whether as a result of new
information, future events or otherwise.
Vertex's press releases are available at www.vrtx.com, or by
fax-on-demand at (800) 758-5804, Code: 938395
Lilly Contact:
Terra L. Fox, Manager, Financial Communications, (317) 276-5795
Vertex Contacts:
Michele Karpf Belansky, Associate Director, Corporate Brand Management,
(617) 444-6259
Michael Partridge, Director, Corporate Communications, (617) 444-6108
SOURCE: Vertex Pharmaceuticals Incorporated
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| Summary
of FDA Peg-Intron Hearing
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This is a report from the FDA hearing held
on Peg-Intron held December 12 . The FDA presented their data analysis
from the large Peg-Intron phase III study of Peg-Intron plus ribavirin
in compared to standard interferon plus ribavirin breaking it down by
genotype and viral load. The FDA reported 28% with genotype1 and hi
viral load receiving standard IFN+RBV had a sustained viral response (SVR)
compared to 29% for those receiving Peg-Intron+RBV 800mg with genotype
1/hi viral load. Regarding patients with genotype 2-6 and low viral load
the FDA reported responses: 74% who received standard IFN/RBV had SVR
compared to 72% receiving Peg-Intron/RBV 800mg. Schering reported
patients with genotype 2/3 & hi-viral load (>2 million) had 77% SVR with
IntronA/Rebetol and 76% SVR with Pegintron 1.5 ug/kg/Rebetol 800mg.
For those patients with lo viral load & genotype 1, PegIntron/RBV showed
72% SVR vs 44% using standard IFN/RBV. For patients with genotype 2-6 &
lo viral load, 72% receiving standard IFN/RBV had SVR vs 81% using
PegIntron/RBV. Schering reported that for genotype 2/3 and <2 million
80% receiving IntronA/Rebetol had SVR and 91% receiving PegIntron 1.5 ug/kg/Rebetol
800 mg had SVR.
Pegasys is still in the FDA review process for approval, which is
expected in the 2nd half of 2002. Therefore, although Pegasys+RBV data
has been presented publicly by Roche, it has not been presented yet by
the FDA nor has the data been published yet. At AASLD at the Roche
symposium in November 2001, Morris Sherman, MD reported data on response
to Pegasys+RBV for various genotypes and viral load levels from their
large phase III study. In persons with genotype 1 and high viral load
(>2 million), 41% receiving Pegasys+RBV 1000-1200mg had an SVR vs 33%
for patients receiving standard IFN+RBV 1000-1200. In patients with
genotype 2/3 and high viral load 74% receiving Pegasys/RBV had an SVR vs
59% receiving standard IFN/RBV.
Differences in response in patients with low viral load were also
reported between Pegasys+RBV vs standard IFN+RBV: genotype 1 + low viral
load - 56% had an SVR receiving Pegasys/RBV vs 44% receiving standard
IFN/RBV; genotype 2/3 + low viral load - 81% had an SVR receiving
Pegasys/RBV vs 65% receiving IFN/RBV.
Ribavirin (RBV) Weight Based Dosing
In the large phase 3 study of Pegintron+RBV only one dose regimen
consisting of 800 mg per day was studied in combination with Pegintron.
Although Schering culled data in a retrospective nature from this study
suggesting therapy may be more effective in terms of antiviral response,
the FDA finds the data inadequate and is requiring Schering to conduct a
large prospective study, which is ongoing. The FDA said the cost/risk
benefit of RBV weight based dosing is not resolved. Data shows more
adverse events occur at higher doses of RBV. The following data on
weight based dosing was gathered from a post hoc (after the study)
retrospective analysis. The FDA expressed several concerns about the
data on weight based dosing from Schering's analysis. Preliminary
antiviral efficacy data suggests benefit to higher dosing, but the
number of patients in parts of the analysis were too small to make
conclusions about the potential anitiviral benefit. For example,
patients receiving <10.7 mg/kg of RBV plus PegIntron 1.5 ug/kg numbered
326 and 156 had a SVR. 126 patients received10.7 to 13.3 mg/kg RBV +Peg
1.5 and 70 had an SVR. This suggests a better SVR for those patients
receiving the higher RBV dose based on weight. But in higher weight
based dosing categories the number of patients were small. Only 38
patients received 13.3-14.7 RBV mg/kg along with Peg 1.5 and 25 had an
SVR. This suggests a better response with higher weight based dosing. In
the higher weight category where only 21 patients received 14.7 or more
mg/kg of RBV, 13 had a SVR. The FDA said the numbers of patients in the
higher dosing groups were too small to draw a conclusion that higher
dosing concentration is beneficial to antiviral effect. The FDA said the
true reason for better response at higher RBV concentration by weight
could be due to patient body weight: body weight could be a surrogate
for RBV dosing. The Schering analysis was not randomized and said there
were additional unknown factors. They felt across arm comparisons were
inappropriate. The FDA data showed patients receiving higher RBV dosing
(>10.7) had more incidence of dose modification (IFN or RBV) for all
causes as well as for anemia and neutropenia. The incidence of anemia
was higher for patients with lower body weight and greater RBV
concentration (>10.7). But the incidence of severe anemia was not
greater. As well, the incidence of neutropenia as well as the incidence
of severe neutropenia was greater for patients at lower body weights &
higher concentration of RBV dosing (>10.7). In HIV/HCV coinfected the
potential for certain adverse events such as decreased hemoglobin
(anemia) and neutropenia may be particularly concerning. Therefore, as
part of the FDA Peg-Intron approval Schering is conducting a phase 4
retrospective study to explore the question of weight-based dosing.
Several committee panelists expressed concern that since the PegIntron
monotherapy study does not show a difference in SVR between the
PegIntron 1.0 dose and the 1.5 dose and since adverse events may be less
using the lower dose, the FDA approved dosing of 1.5 may not be well
founded. But since it has already been approved it may be too late to
make changes. The already in progress phase 4 studies are based on using
the FDA approved 1.5 dose. |
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Expanding the Donor Pool with
Living Donors
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Expanding the Donor Pool with Living Donors
Linda Ohler, RN, MSN, CCTC, Editor in Chief
[Progress in Transplantation 11(3):160-161, 2001. © 2001 NATCO]
Introduction
In the past few months, the Washington Post has covered several
stories about transplantation, organ donation, and artificial hearts
that have made front-page news. These newspaper articles have shed a
positive light on issues we have been facing for several decades: the
supply and demand for organ and tissue donations. In the same period
of media coverage, I participated in a conference on "The Non-
Directed Donor: What's Next by Practice and Ethics," sponsored by the
National Kidney Foundation and held in Boston, Mass. A few days
later, I attended a weeklong intensive bioethics course at the
Kennedy Institute of Bioethics at Georgetown University,
Washington, DC. The media and meetings all addressed a common theme:
increasing organ donation using ethically and morally sound
approaches with living donors.With creative efforts aimed at
increasing the organ supply for those who wait, unique programs for
living donation have become a reality. Living donor and cadaveric
exchanges, paired exchanges, and nondirected donations are
being evaluated as they are implemented in various parts of the
country.
Ethicists, transplant clinicians, organ procurement organizations,
the United Network for Organ Sharing, and government agencies that
oversee transplantation are assessing the implementation of programs
that are utilizing these newer initiatives to meet the demands of
organ and tissue transplantation. The media and public are watching
closely too.
Living Donor and Cadaveric Exchange
An article describing a new initiative appeared recently in the
Washington Post.1 The title, "Organ Exchanges Push Boundaries," at
first sight appeared to have a negative spin. However, the article
was well written and discussed strategies that are used to attract
living donors. The story centered on the country's first reported
living donor and cadaver exchange at the New England Medical Center
in Boston. A mother donated her kidney to a stranger, thus enabling
her 13-year-old son to move to the top of the waiting list for a
cadaveric transplant. Two weeks after her donation to a stranger, her
son received a cadaveric transplant. The mother could not donate her
kidney directly to her son because she had an incompatible blood
type. Thus, she donated one of her kidneys to a stranger with the
same blood type. Programs such as this one are gaining favor in the
United States as the waiting list for kidney transplants grows
longer. With the living donor and cadaveric exchange, a living donor
who is incompatible with a family member or friend donates a kidney
to a compatible person on the transplant list. In exchange for this
gift, the family member or friend of the living donor rises to the
top of the list in his or her blood type. Implementation of this
exchange program has elicited discussions within the public and the
media.
Nondirected Living Donors
A second article in the Washington Post,2 "The Kindness of
Strangers," addressed the growing number of nondirected living
donors. The story nicely describes a man who anonymously donated his
kidney to someone in need after he read about a similar donation in
North Carolina. Nondirected living donors are becoming more common
and are prompting some members of our transplant community to ask if
these gifts are truly acts of pure altruism or if there is some
underlying motive on the part of the donor. Only experience and
prospective studies may hold the answer to that question. Some
ethicists point out that purely altruistic live donations do occur
from donors who have no expectations other than the satisfaction of
giving to someone in need.
Both articles published in the Washington Post were positive and
provided public education on the merits of living donors. These
articles also conveyed the great need for organs and tissues.
Paired Exchange Programs
The paired exchange living donor programs are not unlike directed
living donations. In this situation, a family member or friend offers
to donate a kidney to a loved one but the blood type is incompatible
or there are HLA specificities. Working with the organ procurement
organization or transplant center, this pair then seeks out another
couple or pair with whom blood type may be compatible. Thus, the
kidneys are shared with compatible pairs in what has become known as
a paired exchange.
The Washington Regional Transplant Consortium (WRTC) plans to move
forward with living donor and cadaveric exchanges in the Washington,
DC, area later this year. WRTC has also developed a paired exchange
program and a living donor registry. In addition, WRTC has developed
guidelines for nondirected donors and receives several calls a day
about living donation. This program has been well thought out with
ethicists, physicians, and laypeople participating in the planning.
The United Network for Organ Sharing supports programs such as those
developed at WRTC and the New England Organ Bank (NEOB). Living donor
registries have been endorsed by the Live Organ Donor Consensus
Group, which met in Kansas City, Mo, in 2000.4
The Nondirected Living Donor Conference
The conference on nondirected living donors assembled in Boston on
May 30 and 31, 2001, and was led by Dr Frank Delmonico of Harvard
University. The agenda included topics such as advertising for
donors, process of donor evaluation, informed consent, ethics of
recipient selection, communication between the nondirected donor and
recipient, economics, and donor follow-up. The group included
physicians, ethicists, a social worker, a nurse, a clergyman,
executive directors of NEOB and WRTC, a representative of the
Division of Transplantation, and a representative from the insurance
industry. Important questions regarding the distribution of a
nondirected organ were discussed. Is it the transplant center's organ
to allocate or should the organ go into a regional pool? Participants
of the conference agreed that the cold ischemic time should be
minimized to decrease the risk of delayed graft function.
The group focused its attention on nondirected kidney donors,
recognizing a reluctance of most transplant centers to accept
nondirected living lung or liver lobes with the associated risks for
each procedure. The experience of several transplant centers, NEOB,
and WRTC served as the basis for much of the discussions as ethical
and practice guidelines for nondirected donation were considered. A
paper will be published from this conference, which will address the
recommendations for initial screening of nondirected donors,
determining medical suitability of donors, psychological evaluations
of living donors, recipient selection, compensation, prisoners as
donors, communication between nondirected donors, and recipients and
media attention to the process. A variance for the allocation of
nondirected donations may be needed to ensure fair and equitable
distribution with the shortest ischemic time.
Intensive Bioethics Course at Georgetown University
It was timely that the articles appeared in the Washington Post
during our week of bioethics classes at Georgetown University. The
issues of nondirected donation and living donor and cadaveric
exchanges became points of discussion. Course participants included
200 individuals from 14 countries and at least as many disciplines.
Thus, ethical discussions of altruism, autonomy, nonmaleficence,
informed consent, and beneficence were lively and provocative. In his
book, Transplantation Ethics,3 Dr Robert Veatch of Georgetown
University nicely addresses ethical issues surrounding living
donors, paired exchanges, and live donor and cadaveric exchanges.
This book will be reviewed in the December issue of the Journal.
Perhaps the title of the Washington Post article was not as negative
as I originally feared. It is true; we are pushing the boundaries.
The supply of cadaveric donors is insufficient to meet the needs of
potential recipients; thus, boundaries need to be pushed. It is up to
us to keep the ethical and moral issues on the radar screen as we
test these new strategies. With the multidisciplinary focus of
transplantation, our colleagues in bioethics are sure to keep us on
the straight and narrow.
References
Okie S. Organ exchanges push boundaries. Washington Post. June 9,
2001:1, 10.
Kirsch F. The kindness of strangers. Washington Post Parade. June 10,
2001:1, 4-6.
Veatch R. Transplantation Ethics. Washington, DC: Georgetown
University Press; 2000.
Live Organ Donor Consensus Group. Consensus statement on the live
organ donor. JAMA. 2000;284:2919-2926.
Hepatitis C Research
Gets a Boost
|
Hepatitis C Research Gets a Boost
By Kristen Philipkoski
SAN FRANCISCO -- When researchers at Vertex Pharmaceuticals chose
hepatitis C as the disease they hoped to treat, they didn't realize
the uphill battle they faced. But thanks to new drug discovery
technologies, they've come up with a drug that, if successful, will
work much like many of the drugs effective against HIV.
Drug discovery is not easy. It often takes about 10 years and $5
million to $10 million to bring a drug to market. But there are some
things that can make it harder than normal, such as a disease
molecule that just doesn't want to stick to a drug.
In such cases, many companies give up. Vertex was tempted to, and
would have had no choice a decade ago. But new computer-based
technologies, especially protein structure analysis techniques,
helped them build a potential drug to the exact specifications of
the
hepatitis C disease protein.
"We knit together the biophysics, testing in the lab, the structural
information and all of the processes. That's what we do best,"
Joshua
Boger, the Vertex CEO, said.
Vertex announced the potential drug, a molecule called LY570310,
also
known as VX-950, on Tuesday at the J.P. Morgan H&Q Healthcare
conference. The drug is at the point where they're ready to test it
in animals, and soon after, humans.
Hepatitis C is an infectious disease of the liver that chronically
affects approximately 2.7 million in the United States. It's nearly
always fatal; kills slowly, often with no symptoms; and is usually
caused by intravenous drug use.
The drug is a "hepatitis C protease inhibitor." If that sounds
familiar, it's because the breakthrough drugs for treating AIDS are
also protease inhibitors. Protease inhibitors prevent a virus from
creating infectious copies of itself.
But unfortunately for Vertex researchers, that's where the
similarity
ends.
The HIV protease molecule is physically attractive to drug
designers.
It has what looks like a big tunnel going through it, and
researchers
were able to design a drug that neatly stuck inside.
Vertex researchers figured out exactly what the hepatitis C protease
protein looks like down to the last atom in 1996, but its three-
dimensional structure was a bit disconcerting.
They found its surface was practically smooth, with no big valleys
or
holes to stick a drug into. Instead they saw nothing more than a
slight indentation.
"There was kind of a little dimple on the surface," Boger said.
Researchers have enough trouble making chemical compounds, that will
dock onto a protein to counteract a disease when there is a clear
place to put it. One with no "docking station" poses an even bigger
problem.
Vertex has one drug already on the market for HIV, also a protease
inhibitor called Agenerase, which received FDA approval in 1999.
Finding the chemical compound that eventually became Agenerase was
easy compared to the hepatitis C drug, Boger said.
To find their hepatitis C molecule, Vertex researchers used X-ray
crystallography to analyze the finest details of that little dimple.
Eli Lilly signed on as a partner to find a drug candidate, initially
investing $5 million.
Researchers tried the entire library of Lilly's chemical compounds
against the hepatitis C protein, to no avail.
Pummeling a disease protein with as many chemical compounds as are
available is the old, inefficient method of discovering drugs. Now,
researchers have found ways to guide discovery by analyzing the
physical structure of the proteins.
"The structural information was absolutely essential," Boger said.
Scientists had to create a chemical compound with every atom
positioned in exactly the right spot to fit on the dimple.
Researchers may be able to do two physical tests in the lab per day,
but in the same time they can perform millions of computer
simulations. They combined both to guide their development of a
precisely designed potential drug.
Now that they've identified the hepatitis protease inhibitor, tests
in animals and eventually humans (Vertex hopes), will tell whether
their efforts will result in a marketable product.
1F7 Shows Positive Data for Hepatitis
|
|
VANCOUVER, B.C.--(BUSINESS WIRE) --Jan. 8, 2002--Immune
Network Ltd. (OTCBB:IMMKF)(CDNX:IMM.) announced today the
publication of results with its 1F7 antibody in tests designed
to
find out whetherit may be able to improve the response of the
immune
system toinfection.
The 1F7 antibody is thought to have specific reactivity with
antibodies from both the human immunodeficiency (HIV) and the
hepatitis C (HCV) viruses.
"As others have previously demonstrated for HIV, we
now show that antibodies against HCV share a common structural
feature recognized by 1F7," said Dr. Michael Grant, a member of
the
immunology research group in the Faculty of Medicine at Memorial
University in Canada and collaborator with Immune Network. "It's
reasonable to speculate that antibodies produced in other
chronic
diseases share the same features." Dr. Grant has shown that 1F7
selectively binds antibodies against multiple components of HCV
in
addition to previous studies showing the binding of 1F7 to
anti-HIV
antibodies. This is exciting news, since it means that 1F7 has
the potential to boost the human immune system when either or
both
infections are present. Further work is planned with 1F7 to test
for
its reactivity with antibodies to other viruses causing chronic
infections, to further establish its mechanism of action, and to
develop it as a potential human therapeutic drug.
The Journal of Medical Virology published Dr. Grant's
work under the title "Antibody Convergence Along a Common
Idiotypic
Axis in Immunodeficiency Virus and Hepatitis C Virus
Infections" in its January issue. The abstract can be viewed on
the
World Wide Web at
http://www3.interscience.wiley.com/cgi-
bin/abstract/88511251/START.
Copies of the abstract and the complete publication
can also be obtained from Immune Network. This work was funded
by
Immune Network and by the Canadian Institute for Health
Research.
More about 1F7:
Monoclonal antibody 1F7 has profound effects on the
function of the immune system and the action of immune cells.
Numerous
publications suggest that 1F7 may be able to extend the ability
of
the immune system to generate antibodies against HIV, even after
the
virus mutates, possibly preventing the virus from "escaping"
from the
immune system. Other data from Dr. Grant's laboratory, published
in
Immunology and Cell Biology in February 2000, demonstrated that
1F7
had specific effects on human immune cells (CTL cells) from HIV
infected patients to prevent these cells from killing other
immune
cells (uninfected helper T cells).
If the beneficial effects of 1F7 on the immune system can be
confirmed, it would be an important new approach to the
treatment
of HIV infection and AIDS. Now, with the demonstration that 1F7
has
activity that could have an impact on other chronic viral
diseases
such as HCV, the relevance of accelerating the development of
1F7 is
evident. Immune Network is forming a team in 2002 to develop a
plan
for the clinical evaluation and future commercialization of this
product as well as that of another Immune Network anti-HIV
antibody,
hNM01. Further information on these products and the team
working on
them will be available later in this quarter.
On behalf of the Board of Directors
Allen Bain, Ph.D., CEO
"Safe Harbor" Statement under the Private Securities
Litigation Reform Act of 1995:
This news release contains forward looking statements
that are not historical facts and are subject to risks and
uncertainties which could cause actual results to differ
materially
from those set forth in or implied herein. These risks are
described
in detail in the company's Securities and Exchange Commission
filings.
The Canadian Venture Exchange has not reviewed and
does not accept
responsibility for the adequacy or accuracy of the
content of this news
release.
CONTACT:
Immune Network Ltd.
Investor Relations, 604/222-5541
or 1-877/644-5541 ext. 466
Fax: 604/222-5542
E-mail:
info@i...
Website: www.immunenetwork.com
|
|
|
Heavy Demand Strains Schering?
The following is an article from the Newark Star ledger on the Peg-Intron
wait list.
Two HCV community advocates are quoted, Thelma Thiel of HFI and myself.
Unfortunately the paraphrase of my comments is misleading. To set the
record straight, here is the full quote I actually gave to the reporter:
"The company in its marketing hype for this drug created a backlog of
patients who have been waiting for treatment, yet the company is now unable
to meet demand for the product, so will ration it.
Despite he marketing hype, Peg-Intron+ribavirin is only EQUIVALENT in
efficacy, NOT superior to
standard interferon+ribavirin for the vast majority of patients (Genotype 1
high viral load and all genotype 2/3 patients) as shown in the rigorous
intent-to-treat analysis in its FDA approved label. With this level of
efficacy, there was no medical need to rush this drug to market only to now
create a shortage and frustration for patients and providers".
From analyst sources the following information is also of interest:
"Per the company, there is no Access Assurance
program in Europe. Which of course raises the question, how can you
delay treatment for U.S. citizens if you are not doing the same thing in
the rest of the world? In response to such a question, the company
responded that because the drugs had been available in Europe for quite
some time, there was no surge in demand there - it was the U.S. built-up
pool of patients that they were dealing with.
Interestingly, from a previous statement(s) from SP, the capacity for
PEG-Intron for the U.S. marketplace is about 60,000 patients. One of
our sources thought that even though the document just released says
there are 60,000 patients enrolled in Access Assurance, it was his
belief that there only 20 - 30,000 actually on the drug at this point in
the U.S."
So is the demand really so heavy?
Brian Klein
HAAC-SF
-------------------------------------------------------------------------------------------------------------
Heavy demand strains Schering
01/16/02
BY DAVID SCHWAB
STAR-LEDGER STAFF
Schering-Plough's new treatment for the chronic liver disorder hepatitis C
may be more than the company bargained for.
The company can't make enough of the drug Peg-Intron to keep up with demand
and expects to begin putting patents on a waiting list for the treatment
shortly.
Kenilworth-based Schering- Plough and some patient activists say any delay
shouldn't pose a serious medical problem, in part because other treatments
are available and because the disease often remains dormant in the body for
years.
But the company's inability to make enough of the drug eventually could cost
it tens of millions of dollars in lost sales, as Immunex Corp. found out
with its new arthritis drug, Enbrel.
Shares of Schering-Plough fell 97 cents yesterday, or 2.8 percent, to close
at $34.20.
In addition, some activists say they don't like the idea of Schering- Plough
or any company making decisions about waiting lists. That they would rather
leave to doctors.
"I would have to be a little concerned about it myself," said Thelma Thiel,
chairman of the Hepatitis Foundation International in Cedar Grove. Four
million Americans are infected with hepatitis C.
Schering-Plough spokesman Robert Consalvo said patients with an urgent
medical need will not have to go on a waiting list. An independent medical
review board will study such cases.
Consalvo said the company expects patients placed on the waiting list to
receive the medicine by April.
Before any talk of waiting lists, 60,000 patients signed up for the new
hepatitis C treatment, which became available last October, according to
Schering-Plough. Hepatitis drugs are the company's second-biggest sellers,
after the allergy blockbuster Claritin.
The hepatitis treatment consists of a daily injection of Peg-Intron and
capsules called Rebetol, a combination that is supposed to be better than
the previous treatment called Intron-A.
The problem is that tens of thousands of patients were waiting for the new
treatment to be approved by the Food and Drug Administration, so there was a
sudden surge of demand when the products went on sale. So Schering- Plough
instituted a special program requiring patients to register in order to get
the drug, which must be taken for 48 weeks.
The shortages are compounded by the fact that Peg-Intron is a complex
biological product that requires more time to grow and more specialized
manufacturing facilities than conventional drugs, which essentially are
mixtures of chemicals.
Schering-Plough manufactures Peg-Intron at a plant in Brinny, Ireland, which
is running at full capacity, Consalvo said.
Brian Klein of the Hepatitis C Action and Advocacy Coalition said a
potential shortage is not a big deal because the new hepatitis treatment is
no better than the older treatment, Intron-A.
The creation of a waiting list "only creates frustration and anxiety for
patients," he said.
David Schwab can be reached at dschwab@starledger.com or (973) 392-5835.
Schering may resort to waiting list for drug
NEW YORK (Reuters) - Schering-Plough Corp., citing insufficient supplies of
its PEG-Intron treatment for chronic hepatitis C, said on Tuesday it may
resort to a waiting list for patients seeking the drug.
"The overwhelming response to PEG-Intron and Rebetol combination therapy
since its launch has recently led the company to conclude that demand for
PEG-Intron would exceed its near-term ability to ensure supply of product in
the United States at current new-patient enrollment rates," the company said
in a statement.
Goldman Sachs analyst James Kelly said in a research note that supply
constraints could limit sales gains for the drug in 2002. Schering-Plough
declined to discuss the company's manufacturing capacity of its fastest
growing medicine and the second-largest product.
Schering-Plough said it started what it calls an "access assurance" program
in October that is aimed at tracking how much drug is needed and that
patients would be granted a continued supply. The waiting list is expected
to start for newly enrolled patients in the next 10 days, the company said.
Patients on the waiting list would be expected to begin treatment in about
10 to 12 weeks, the company said.
Schering-Plough's biotechnology production facility in Ireland is running at
full capacity for PEG-Intron and the company is building another
biotechnology facility in Singapore for PEG-Intron and other products, the
company said.
The combination therapy of PEG-Intron and Rebetol is used for a 48-week
period, rather than for a lifetime, as is the case with other therapies,
Schering-Plough spokesman Robert Consalvo said.
Shares of Kenilworth, New Jersey-based Schering-Plough were down $1.07 at
$34.10 in late afternoon trading on the New York Stock Exchange.
Shares of Enzon Inc., which receives a royalty for technology used to make
PEG-Intron, fell 4.4 percent, or $2.37, to $51.52. Enzon shares were as low
as $49 during the day's trading.
Kelly said in a research note that the "wait list" procedure to enroll
patients in the hepatitis treatment program could limit sales gains in 2002.
"This will limit the total pool of patients to approximately 60,000
individuals for the near-term," said Kelly, who has a "market outperformer"
rating on Schering-Plough.
Consalvo said 60,000 patients in the United States are enrolled in the
access assurance program, so far. This also includes some patients who were
receiving treatment before the access assurance program was started in
October.
Consalvo did disclose Schering-Plough's production capacity of the drug or
the total number of patients.
The capacity problems are reminiscent of those last year at biotech firm
Immunex Corp., whose rheumatoid arthritis drug Enbrel had sales capped at
$750 million last year when demand could have easily increased that figure.
There is enough PEG-Intron to treat all patients currently receiving
therapy, at an estimated wholesale cost of $22,000 for the average American
patient's treatment of PEG-Intron and Rebetol.
The latest combination is about 60 percent effective in eliminating the
hepatitis C virus, compared with 50 percent for Rebetron, which was Intron-A
and Rebetol. PEG-Intron is a more potent and longer lasting version of
Intron-A developed using Enzon's polyethylene glycol technology.
Consalvo said the company is establishing an independent medical board to
review urgent requests for PEG-Intron therapy and it is allocating some of
its supplies to meet emergencies.
Through the access assurance program, Schering-Plough will not have
individual patient information but will only monitor usage of the drug.
15:53 01-15-02
Copyright 2002 Reuters Limited. All rights reserved.
First Monoclonal Antibody in the Clinic to Show Activity Against
The Hepatitis C Virus
REHOVOT, Israel, Jan. 14 /PRNewswire/ -- XTL Biopharmaceuticals Ltd.
(LSE: XTL) today announces positive clinical data on the antiviral
activity and safety of XTL-002, being developed for the treatment of
hepatitis C virus (HCV) infections. Results of the Phase Ia study, which
included 15 chronic HCV patients, indicate that HCV viral RNA levels were
reduced in over half the patients following a single dose. No serious
adverse events were reported.
The single-centre study, under the regulation of the United States Food and
Drug Administration (FDA) and Ministry of Health, Israel, was designed to
test safety, tolerability and efficacy of a single-dose of XTL-002 in
chronic HCV patients. The 15 patients were divided into 5 groups, with each
group receiving 0.25, 1.0, 2.5, 10 or 40mg of XTL-002 in a single
intravenous infusion. HCV viral RNA levels were measured pre-infusion and at
multiple time intervals following infusion of XTL-002. In 8 out of 15
patients, significant reduction of HCV viral RNA, ranging from 2 to 100
fold, was demonstrated following XTL-002 administration.
XTL-002 is a fully human high-affinity monoclonal antibody which was
shown to reduce viral levels of the HCV virus in XTL's proprietary in
vivo model, the HCV TrimeraXTL model. This model is being used in
conjunction with a variety of corporate and academic partners to screen and
evaluate novel compounds to treat HCV. A peer reviewed scientific article on
XTL's HCV TrimeraXTL model was recently published in the Journal of
Infectious Disease.
Professor Eithan Galun, Director, Goldyne Savad Institute of Gene
Therapy, Hadassah University Hospital and a principal investigator in the
study, commented:
"XTL-002 is a promising new therapeutic modality for treating chronic
HCV patients. In addition, XTL-002 could be employed to prevent HCV
re-infection in HCV-associated liver transplant patients, where no drug
currently exists."
Martin Becker, Ph.D., President and Chief Executive Officer of XTL,
said:
"XTL is the first company to initiate clinical trials with a monoclonal
antibody against HCV. We are pleased that the clinical results with XTL-002,
though early-stage, suggest that XTL-002 is active against the HCV virus.
XTL-002 is the most advanced drug in our broad HCV program, which includes
multiple drug candidates that are either fully owned by XTL or co-developed
with corporate partners."
Hepatitis C is a major public health concern. The World Health
Organization estimates that 170 million people worldwide are chronic
carriers of the hepatitis C virus, with 4 million carriers in the United
States alone. It is estimated that 25-35% of these chronic patients will
develop progressive liver disease including cirrhosis and liver cancer.
Hepatitis C is the leading cause of liver transplantation. The Center for
Disease Control estimates that in the year 2000, about 10,000 people died in
the US as a result of HCV. It is predicted that by the end of this decade,
the number of deaths in the US as a result of HCV will surpass the number of
deaths from AIDS.
Notes
XTL Biopharmaceuticals develops novel therapeutics to treat
life-threatening infectious diseases using fully human monoclonal antibodies
and small molecule drugs. XTL's competitive advantage lies in its ability to
leverage both its proprietary human tissue-based in vivo disease models and
fully human monoclonal antibodies to validate and develop promising drug
candidates. The Company's growing pipeline of therapies, designed to combat
chronic viral infections, drug-resistant bacteria and serious systemic
fungal infections, comprises internally developed products as well as those
being co- developed with a number of biopharmaceutical partners. For more
information about XTL, visit the Company's web site at www.xtlbio.com .
SOURCE XTL Biopharmaceuticals Ltd
Research Needed To
Understand Poor Outcome In African-Americans/Asian Liver Transplants
Lancet
01/24/2002
By Harvey McConnell
African Americans and Asians have a worse outcome after orthotopic liver
transplantation compared with white Americans and Hispanics.
"The higher rate of chronic rejection in African Americans and a relatively
worse outcome in other minority races merits further examination, " declares
Dr Paul Thuluvath and colleagues from the Division of Gastroenterology Johns
Hopkins University, Baltimore, Maryland.
Dr Thuluvath base his contentions on a study of data from the United Network
of Organ Sharing transplant registry for all liver transplants done between
1988 and 1996 in the United States. The researchers also recorded
information on age, sex, race, blood group, and cause of death for the
donors and recipients.
Due to an overall increase in the number of liver transplantations, a large
number of African Americans, Hispanics, and Asians have undergone orthotopic
liver transplantation (OLT) in the past decade, the clinicians point out.
"From published reports, it is not clear whether there is a difference in
survival among the different races following OLT. There is significant
evidence to suggest that the long-term survival in African Americans is
lower compared with white Americans after renal transplantation."
Inferior histocompatibility matching, poor compliance, and a lower
socioeconomic status have been implicated for the poor survival among
African Americans. However, it is unclear whether these observations might
be extrapolated to patients undergoing OLT. A few studies have analyzed the
survival among African Americans after OLT, with conflicting results.
The study found that two-year graft survival was significantly lower for
African Americans (601 of 884 - 68 percent) and Asians (266 of 416 - 64
percent) compared with white Americans (8,703 of 11,762 - 74 percent ) and
Hispanics (878 of 1,220 - 72 percent).
Patients' two-year and five-year survival were significantly lower for
African Americans: 654 of 884 (74 percent) at two years, and 270 of 565 at
five years (48 percent). Among Asians, the comparable figures were 287 of
416 (69 percent) at two years, and 92 of 252 (37 percent) at five years.
Among white Americans, similar figures were 9,786 of 11,762 (83 percent) at
two years, and 4,357 of 7,514 (58 percent) at five years. Comparable figures
among Hispanics were 964 of 1,220 (79 percent) at two years, and 341 of 657
(52 percent) at five years.
Race was an independent predictor of poor two-year survival, with African
Americans and Asian patients having an increased risk profile of 36 percent
and 25 percent, respectively, when compared with white Americans.
Dr Thuluvath concludes: "Our study suggests that there is a clear need for
prospective studies to examine our observations further. Until then, the
reasons for poor survival in African Americans will remain speculative and
will probably be dismissed as being due to poor compliance with therapy.
"Moreover, the higher rate of chronic rejection in African Americans
suggests that there should be more rigorous drug trials in this patient
population."
Lancet 2002; 359: 287-93.
Idun Pharmaceuticals' Clinical Trial Demonstrates
Safety Of Liver Disease Drug
Phase I Trial Demonstrates Safety and Opens the Door To Treat Multiple
Liver Diseases
SAN DIEGO, Jan. 31 /PRNewswire/ -- Idun Pharmaceuticals, Inc. today
announced the results of its Phase 1 clinical trial of IDN-6556. The drug
was safe and well tolerated in a clinical study involving 50 normal adults.
Evaluation of patients with mild hepatic impairment is ongoing. In the Phase
1 study, IDN-6556 was administered in both single doses and for a week of
therapy with various doses. The drug was well tolerated in all groups of
subjects.
"We are excited to have completed this Phase 1 stage of the drug's
development," said Dr. David Shapiro, Chief Medical Officer and Executive
Vice President at Idun. "This drug may prove to be useful in multiple liver
diseases and we will shortly start Phase 2 studies to evaluate its effects
on different groups of hepatic patients. We will conduct Phase 2 trials of
individuals with hepatitis C virus (HCV) infections, alcoholic liver disease
and, subsequently, additional trials of individuals experiencing acute
alcoholic hepatitis. HCV affects about 4 million Americans and another 200
million people worldwide. Acute alcoholic hepatitis is an often-lethal
condition that affects about 85,000 people in the U.S. alone and for which
there is no effective treatment. We believe that IDN-6556 can play an
important role in the standard care for people with HCV, acute alcoholic
hepatitis, and many other liver diseases."
"There are literally more than a half-billion people in the world
suffering with liver diseases that may benefit from this drug," added Dr.
Steve Mento, Idun's President and CEO. "The success of the Phase 1 trial of
our caspase inhibitor is the first clinical step to a new and important
therapy for patients with liver disease. It also validates Idun's approach
to small molecule drug development and the role that apoptosis modulators
can play in the treatment of a number of diseases. We've always believed
that caspase inhibitors would be effective drugs for a number of diseases.
IDN-6556 is the first broad-spectrum caspase inhibitor to be studied in
humans.
"This is just the beginning of many exciting new opportunities that can
come from Idun's technology. We have programs in earlier stages of
development in cardiovascular disease, inflammation, central nervous system
diseases, and cancer with just as much potential."
Idun Pharmaceuticals, Inc. is a biopharmaceutical company located in San
Diego, CA, creating innovative human therapeutics with a primary focus on
controlling apoptosis, or programmed cell death. Apoptosis is a genetically
controlled normal physiological process mediated by a cascade of
intra-cellular proteins. Too much, inappropriate, or too little apoptosis is
believed to play a role in many important human diseases. Idun believes that
controlling the cell death process will have utility in treating cancer,
neurodegenerative diseases, ischemic disorders and cardiovascular disease.
The company has adopted a commercialization strategy encompassing strategic
collaborations with major pharmaceutical companies; internal, independent
development of selected small molecule therapeutics; and out-licensing of
diagnostics, gene therapies, and bioproduction technologies. Idun has an
extensive patent portfolio covering the fundamental and core technologies
involved in the regulation of cell death and has established partnerships
with Abbott Laboratories in cancer, with Elan Corporation, plc in stroke,
and Becton Dickinson and Company in research reagents.
Some of the statements in this press release are forward-looking
statements and do not guarantee future performance and involve risks and
uncertainties. Actual results may differ substantially from the results that
the forward-looking statements suggest for various reasons. These forward-
looking statements are made only as of the date of this press release.
SOURCE Idun Pharmaceuticals, Inc.
CO: Idun Pharmaceuticals, Inc.
ST: California
IN: MTC BIO
SU:
01/31/2002 08:02 EST
http://www.prnewswire.com
Roche confident new data will let Pegasys drug fly
LONDON, Jan 29 (Reuters) - Swiss healthcare group Roche Holding AG said
on Tuesday it would have new data on its key Pegasys drug for hepatitis C by
early March, paving the way for the product's launch in the second half of
the year.
Roche is relying on the interferon medicine to revive its fortunes after
a dismal year of product setbacks and weak sales.
But the drug has been delayed several times and the company needs to
provide ``bioequivalence'' data to the U.S. Food and Drug Administration to
prove that material from new production capacity is identical to earlier
batches.
Jonathan Knowles, head of research, said Roche would be in a position to
go back to the FDA with the information by the end of the first quarter.
``Things are looking good... I'm quietly confident,'' Knowles said during
a presentation on Roche's alliance with Icelandic genomics firm deCODE
Genetics Inc (NasdaqNM:DCGN - news) in London.
Last October, Roche pushed back the expected launch date for Pegasys to
the second half of 2002 because of the bioequivalence problem. It had
already delayed in August its forecast for initial sales to the first half
2002.
The delay is a blow to Roche because Schering-Plough Corp (NYSE:SGP -
news) has already launched its rival PEG-Rebetron product in the United
States. Industry analysts fear Roche will not be able to make an impact with
its product until 2003. |
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