| Ribapharm
sues to block Roche rival hepatitis C drug
NEW YORK, Aug 26 (Reuters) - Ribapharm Inc. <RNA.N> on Monday said it
had filed a lawsuit to prevent Swiss drug maker Roche Holding Ltd. <ROCZg.VX>
from selling a hepatitis C treatment in the United States that would
compete with Ribapharm's big-selling pill called ribavirin.
The Costa Mesa, California firm earlier this month had already filed
suits against Roche in the Netherlands and Germany, alleging the Swiss
pharmaceuticals giant would be violating its patents if it were to
launch its own form of ribavirin to treat hepatitis C.
Ribapharm filed its latest suit against Roche in U.S. District Court
in Los Angeles, saying it intends to enforce its U.S. patents on
ribavirin, a pill that Ribapharm licenses to Schering-Plough Corp <SGP.N>.
Ribapharm spokesman Joe Schepers said Ribapharm has patents in the
United States, Europe and Japan that exclusively allows its form of
ribavirin to be used against hepatitis C.
"We're saying to Roche that we have these patents and if you violate
them by selling ribavirin we will seek damages against you and may
ultimately seek an injunction to stop continued sales of your product,"
Schepers said.
But Roche spokeswoman Pamela Van Houten said her company has every
right to sell ribavirin and hopes to get a green light from U.S.
regulators as soon as early December.
"For the U.S., we believe the Ribapharm patents are invalid," she
said.
Roche has said it is entitled to sell its own form of ribavirin
because no patents stand in its way and it has conducted its own
clinical trials of the hepatitis C drug.
Schering-Plough sells ribavirin and an injectable interferon called
Peg-Intron -- which when taken together for 48 weeks are able to
eliminate the hepatitis C virus in more than half of patients with the
often-deadly disease.
An estimated 4 million Americans are infected with hepatitis
C, a blood-borne virus which quietly attacks the liver for years
before symptoms or liver failure appear. The disease is the biggest
cause of liver transplants in the United States.
Use of Peg-Intron together with ribavirin is considered the current
gold standard of treatment for hepatitis C, making the combination
treatment the second-biggest product line for New Jersey-based
Schering-Plough.
Combined sales of the two Schering-Plough drugs more than doubled to
$659 million in the second quarter after legions of hepatitis C patients
on a waiting list began treatment.
But Roche is expected later this year to challenge the
Schering-Plough franchise by launching two similar hepatitis C drugs in
the United States -- its own interferon product called Pegasys and its
own form of ribavirin called Copegus. Pegasys was approved in Europe in
June.
Much is at stake for tiny Ribapharm, which is heavily reliant on
royalties from ribavirin. Industry analysts have predicted
Schering-Plough will pay Ribapharm royalties of up to $250 million this
year and up to $290 million in 2003 on ribavirin sales, compared with
royalties of $143 million in 2001.
Shares of Ribapharm were down 8 cents to $5.77 in Monday afternoon
trade on the New York Stock Exchange, while shares of Roche eased
slightly in Switzerland.
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The Business of Organ Transplants
Friday, August 30, 2002
FRIDAY, Aug. 30 (HealthScoutNews) -- The Transplantation Society
issued a statement today reiterating its position against the buying and
selling of human organs and calling on all countries to outlaw
commercial trafficking in tissues and organs.
The society, which has 3,000 members in 65 countries, issued the
statement on the final day of its international congress in Hollywood,
Fla.
The buying and selling of organs is a hot topic. There have been
suggestions that financial incentives be used to address organ
shortages. There have also been a number of recent news reports about a
growing black market in transplant organs and tissues.
Anyone who applies for membership in the Transplantation Society must
sign a statement that says, "Organs and tissues should be freely given
without commercial consideration of financial profit."
Prospective members also must agree with the society's recommendation
that, "all countries should enact legislation forbidding all commercial
trafficking in tissues and organs. No transplant surgeon/team shall be
involved directly or indirectly in the buying or selling of
organs/tissues or in any transplant activity aimed at commercial gain to
himself/herself or an associated hospital or institute."
The statement was created by the Transplantation Society's ethics
committee in 1986.
"Since arriving at our position in 1986, the ethics committee has,
over the years, maintained a consistent position regarding the selling
of organs. In the current climate, it is even more important that the
Transplantation Society take seriously its role of monitoring and
policing transplantation activity in order that such activity adheres to
the proper principles of practice," says ethics committee member Dr.
Eduardo A. Santiago-Delpin.
More information
Here's an overview on Organ Transplants.
(SOURCE: Transplantation Society, news release, Aug. 30, 2002) |
Date: Wed Aug 28, 2002 1:11 am
Researchers develop model
to predict post-transplant survival in liver transplant patients
SourceURL:http://www.gastrohep.com/news/news.asp?id=1520
Researchers develop model to predict post-transplant survival in liver
transplant patients
Survival following liver transplantation can be accurately predicted
based
on a model using 8 straightforward factors, finds a study reported in the
September issue of the Annals of Surgery.
Researchers from California and Pennsylvania, USA, developed a prognostic
model that determines patient survival outcomes after orthotopic liver
transplantation (OLT), using readily available pretransplant variables.
Variables that may affect patient survival following OLT were analyzed in
hepatitis C (HCV) recipients at the authors' center. This was because HCV
is the most common indication for OLT.
The resulting patient survival model was examined and refined in both HCV
and non-HCV patients in the United Network for Organ Sharing (UNOS)
database.
Among HCV recipients, mortality was predicted using recipient age,
recipient creatinine levels, donor female gender, and urgent UNOS
classification.
The above variables, in addition to donor age, total bilirubin,
prothrombin
time (PT), retransplantation, and warm and cold ischemia times, were then
applied to the UNOS database.
Of the 46,942 patients transplanted over the last 10 years, 25,772
patients
had complete data sets.
An 8-factor model that accurately predicted survival was derived.
A post-transplantation mortality index was calculated using a combination
of these variables, and was applicable to first or second liver transplants.
Patient survival rates, based on model-predicted risk scores for death
and
observed posttransplant survival rates, were similar.
Additionally, the model accurately predicted survival outcomes for HCV
and
non-HCV patients.
Dr Rafik M. Ghobrial, of the David Geffen School of Medicine at UCLA, Los
Angeles, California, said on behalf of fellow authors, "Post-transplant
patient survival can be accurately predicted based on 8 straightforward
factors."
"The balanced application of a model for liver transplant survival
estimate, in addition to disease severity, would markedly improve survival
outcomes and maximize patients' benefits following OLT," it was concluded.
Ann Surg 2002; 236 (3): 315-23,
28 August 2002
New techniques may boost
tolerance of donor organs
Last Updated: 2002-08-27 10:01:05 -0400 (Reuters Health)
By Alicia Ault
NEW YORK (Reuters Health) - Suppressing the immune systems of organ
recipients before transplant and then reducing or even eliminating
immunosuppressant drugs after transplant seems to promote acceptance of the
new organ, at least for a short period of time, according to new research
to be presented this week.
The researchers also found that giving recipients infusions of stem cells
and other types of tissue from living donors before transplant appeared to
block rejection.
The studies are being presented in Miami, Florida, at the XIX
International
Congress of the Transplantation Society.
Tolerance means that the recipient's immune system accepts a transplanted
organ as the body's own. This is an elusive goal; the immune system will
generally reject the new organ if immunosuppressant drugs are not given.
High-dose immunosuppression has been successful, but can make a person
more
susceptible to infection. The drugs can also have extreme side effects.
Even with immunosuppression, half of kidneys from living or cadaveric
donors will be rejected within 10 to 12 years, said Samuel Strober, a
Stanford University professor and transplant pioneer.
Strober and colleagues were able to wean two of four kidney transplant
recipients off immunosuppressives within a year of undergoing their
experimental protocol. The recipients were given both stem cells and a
kidney from the same donor. All four donors did not match the tissue type
of the recipients.
Weeks before the transplant, the four donors were given drugs to boost
stem
cell production. The kidney was transplanted, and then, beginning the day
after surgery, recipients had 10 radiation treatments, targeted at the
lymph nodes, spleen and thymus, to weaken immune system function. They were
also given thymoglobulin to deplete immune system T cells. Then, the stem
cells were transfused into the recipients.
For 2 to 3 months, three patients showed signs of donor and host cell
mixing, or chimerism. Two showed no immune system reaction to the donor
cells, and those two had been completely weaned off immunosuppressive drugs
by one year post-transplant.
But after 5 months of being drug-free, the patients showed signs of
rejection. They were treated and returned to low-dose immunosuppression.
The third patient is about to be weaned completely, and the fourth was
never weaned because of rejection.
In another study, Indian researchers transplanted kidneys into 43
patients
after infusion of stem cells from the same donor into their blood, marrow,
liver and thymus gland. Thirty-two were weaned off drugs within a year.
They are rejection-free, said H. L. Trivedi of the Institute of
Transplantation Sciences in Gujarat, India.
In another study by the same group, 26 patients were drug-free 3 months
after surgery. They had received stem cell infusions into their blood and
marrow before transplantation, and were also given infusions of crushed
donor kidney tissue directly into the thymus 19 days before surgery--if
from a living donor--and during transplant if from a cadaveric donor.
Scientists from the Thomas E. Starzl Institute at the University of
Pittsburgh presented results of several tolerance trials. Kareem Abu-Elmagd
and colleagues gave 22 candidates for small intestine transplants a
one-time dose of thymoglobulin before surgery. Seventeen were receiving
grafts that had been irradiated before transplant. Fifteen of the 22 met
criteria for weaning, which began 90 days post-transplant. They were
started with a single dose of tacrolimus daily for a few weeks; patients
were monitored for rejection clinically and through endoscopic biopsies.
With no rejection, they were moved to an every-other-day dosing, and then
to once a week. Four of the 15 had weaning delayed, and another three
developed rejection. One is on once-weekly dosing, and five are on an
every-other-day dose, Abu-Elmagd said.
On Wednesday, Starzl will report similar success rates in weaning kidney
and liver transplant recipients with the same protocol, and suggested that
the current practice of high-dose immunosuppression should stop.
"What we're looking at here is drastic reduction of immunosuppression,
and
that, of course, is a necessary step...if you're going to get real
tolerance," Starzl said at a press briefing.
Several transplant experts disagreed, saying that tolerance was not that
simple. Megan Sykes, of the Massachusetts General Hospital, said that
despite promising studies, "our understanding of human (tolerance) right
now is very limited."
Alan Kirk, from the National Institutes of Health, said no patient should
reduce their immunosuppressive regimen just because of the upbeat results.
"None of these protocols are ready for prime-time as it were," said Kirk,
adding that, "the important thing is that they go forward so we can learn
how to make them generally applicable."
Copyright © 2002 Reuters Limited
News from Hepatitis Week of September 8, 2002 / Vol. 2 No. 36
Early Study Results Show New
Interferon Effective for Hepatitis C
Early results from studies show that GenOdyssee's new interferon drug for
the treatment of the hepatitis C virus and cancer are up to 100 times more
effective than similar drugs currently on the market.
The studies compared GenOdyssee's nine IFN alpha variants to the
currently marketed IFN alpha 2a and 2b variants in viral infectious disease
models for hepatitis C and immunotherapy models for cancer.
"GenOdyssee's interferons display excellent toxicity profiles and are
much more specific and active than interferons 2a and 2b that are currently
on the market for hepatitis C and cancer," said researcher Michael Tovey,
viral oncology laboratory director at the French National Center for
Scientific Research.
Tovey said the significant improvements shown in preclinical results
could herald a major advance in patient treatment for both conditions.
Study Finding
Pegylated Interferon Superior Said Flawed
A recent study pointing to the superiority of the pegylated interferon drug
Pegasys is flawed, according to the co-director of the Center for Liver
Disease & Transplantation at Columbia Presbyterian Medical Center in New
York.
The study authored by Dr. David Bernstein, director of hepatology at
North Shore University Hospital in New York, reported that Pegasys appears
to provide a better quality of life for hepatitis C patients (see
earlierHepatitis Week story).
Writing in the September issue of Hepatology, Dr. Robert S. Brown Jr.,
said flaws in the study weaken the researchers' conclusions, although he
acknowledged that Pegasys probably does offer an advantage.
The major flaw, according to Brown, is the "inappropriate" pooling of
data. He said the improprieties involved the pooling of doses on the
pegylated interferon side and comparing the results without doing the same
for the interferon group.
"Interferons have dose-dependent side effects, yet there was no
consideration in the final analysis for the different dosing in each of the
constituent trials," Brown said. "The different doses will impact both
potential side effects and efficacy in opposite directions."
"Unfortunately, this report does not meet the standards of reporting
quality of life data, " Brown said. "The conclusion that Pegasys is better
tolerated and offers an improved quality of life compared to interferon 2a
cannot be supported without appropriate pooling of data and dose-specific
comparisons."
Bernstein replied that he and his colleagues strongly believe the
conclusions reached in their report are valid, noting that the methodology
used in the study for pooling of the data and dose-specific comparisons have
been appropriate. "We have properly concluded that pegylated interferon
alfa-2a at a dose of 180 µg/mL is better tolerated and offers improved
health-related quality of life over standard interferon alfa-2a therapy," he
said.
Maxim Advances Enrollment of
Ceplene Phase 2 Clinical Trial in Hepatitis C Nonresponder Patients
Data Safety Monitoring Board Reports Interim Safety Review and Recommends
that Maxim Complete Phase 2 Clinical Trial of Ceplene(TM) Triple-Drug
Combination Therapy
Tuesday September 10, 3:17 am ET
SAN DIEGO--(BUSINESS WIRE)--Sept. 10, 2002-- Maxim Pharmaceuticals (Nasdaq:MAXM
- News; SSE:MAXM) today announced that the Data Safety Monitoring Board (DSMB)
responsible for reviewing its Phase 2 trial of Ceplene (histamine
dihydrochloride) for the treatment of hepatitis C nonresponder patients has
concluded that there have been no safety concerns associated with the
triple-drug combination of Ceplene, Peg-Intron® (peginterferon alfa-2b) and
Rebetol® (ribavirin, USP).
The randomized, controlled Phase 2 study is designed to compare the
treatment of nonresponder hepatitis C patients with a triple-drug
combination of Ceplene, Peg-Intron and Rebetol versus treatment with Peg-Intron
and Rebetol combination therapy alone. The study will include up to 282
patients who failed to respond to prior therapy with the combination of
interferon-alpha and ribavirin. The DSMB reported to Maxim that it has
reviewed the safety data through 12 weeks of treatment for the first 41
patients enrolled in the trial, and has concluded that there have been no
safety concerns and that the trial should proceed under its approved
protocol.
"This report from the DSMB is an important step in the development of
Ceplene as this study represents the first time that Ceplene has been
administered in humans in combination with Peg-Intron and Rebetol for the
treatment of hepatitis C," said Philippe Prokocimer, M.D., Maxim's Vice
President of Drug Development. "As with any new drug combination, patient
safety is a primary concern. We are pleased that initial results from this
large Phase 2 study support the feasibility of adding Ceplene to the current
standard of care in an attempt to improve the treatment of hepatitis C
patients who have failed prior treatments."
The DSMB includes world-leading clinicians experienced in the treatment
of hepatitis C who review the safety data from this Phase 2 clinical trial
on an ongoing basis. Maxim is conducting the Phase 2 trial under an
agreement whereby Schering Corp., a division of Schering-Plough Corp., is
contributing two of its products, Peg-Intron and Rebetol, and performing the
viral testing for the study.
The Maxim Phase 2 trial is designed to evaluate the Ceplene triple-drug
combination therapy for the treatment of nonresponder patients infected with
hepatitis C who failed to respond to prior therapy. Patients will be treated
for up to 48 weeks and followed for an additional 24 weeks after completion
of treatment. The primary measures of efficacy in the study are sustained
complete viral response and sustained biochemical response (normalization of
the liver enzyme ALT, a standard measure of liver function) at 72 weeks. The
trial is being conducted in Western Europe and Israel.
Hepatitis C
Hepatitis C is the leading blood-borne infection in the United States.
The U.S. Center for Disease Control and Prevention estimates that over 4.5
million Americans are infected with the hepatitis C virus. The World Health
Organization and other sources estimate that at least 200 million people are
infected worldwide. Hepatitis C is a viral infection in which oxidative
stress causes inflammation and tissue damage in the liver and, in many
cases, permanent cirrhosis (scarring). The cycle of disease from infection
to significant liver damage can take 20 years or more. Some experts estimate
that without substantial improvements in treatment, deaths from hepatitis C
will surpass those from HIV. Hepatitis C is the leading cause of liver
cancer and the primary reason for liver transplantation in many countries.
The standard treatment for hepatitis C is interferon-alpha, an
immunotherapeutic agent given in combination with the anti-viral drug
ribavirin. The most recent advance in hepatitis C therapy approved for sale
is a pegylated, or sustained release, formulation of interferon-alpha given
in combination with ribavirin. Even with recent advances, approximately half
of patients still do not attain a sustained response with current therapies.
"While we need to continue to improve the treatment available to all
hepatitis C patients, the largest unmet need today is patients who have
failed prior therapy," stated Larry G. Stambaugh, Maxim's Chairman and Chief
Executive Officer. "The steady accumulation of patients over the past
several years who have failed existing therapies has resulted in a large
population of patients in need of the next generation of treatment, and this
group is the focus of our current Phase 2 trial."
Overview of Ceplene and Maxim Pharmaceuticals
Research has shown that oxygen free radicals released by certain immune
cells can suppress the immune system and damage normal tissue, a process
commonly referred to as oxidative stress. Oxidative stress, implicated in
numerous diseases, is most pronounced in the liver and can damage or destroy
liver tissue in patients with hepatitis and other chronic liver diseases.
Ceplene, based on the naturally occurring molecule histamine, has been
shown in preclinical work to prevent the production and release of oxygen
free radicals, thereby reducing oxidative stress. Accordingly, treatment
with Ceplene has the potential to prevent or reverse damage induced by
oxidative stress, thereby protecting critical cells and tissues, including
the liver.
In addition to hepatitis C, Ceplene is currently being tested in Phase 3
clinical trials for advanced metastatic melanoma and acute myelogenous
leukemia, and Phase 2 trials of Ceplene have been completed in advanced
renal cell carcinoma (kidney cancer). Clinical trials are also planned in
chronic liver diseases such as nonalcoholic steatohepatitis (NASH) and
alcoholic liver disease (ALD). More than 1,400 patients have participated in
the company's completed and ongoing clinical trials. Ceplene is an
investigational drug and has not been approved by the U.S. Food and Drug
Administration or any international regulatory agency.
Maxim Pharmaceuticals is a global biopharmaceutical company with a
diverse pipeline of therapeutic candidates for life-threatening cancers,
hepatitis C and other chronic liver diseases. Maxim's research and
development programs are designed to provide hope to patients most in need
by developing safe and effective product candidates that extend survival
while maintaining quality of life. Maxim has attracted an experienced
international management group and a team of employees dedicated to
commercializing life-enhancing product candidates. Joining this motivated
team in its mission are world-leading scientific and clinical investigators
and major pharmaceutical development partners.
In addition to Ceplene, Maxim is also developing small-molecule
inhibitors and activators of programmed cell death, also known as apoptosis,
that may serve as drug candidates for cancer, cardiovascular disease and
other degenerative diseases. Furthermore, the company's MaxDerm(TM)
technology is designed for the treatment of medical conditions for which
topical therapy is appropriate such as oral mucositis, herpes, decubitus
ulcers, shingles, burns and related conditions.
This news release contains certain forward-looking statements that
involve risks and uncertainties. Such forward-looking statements include
statements regarding the efficacy and intended utilization of Ceplene, the
apoptosis modulator compounds and MaxDerm, and regarding the Company's
clinical trials. Such statements are only predictions and the Company's
actual results may differ materially from those anticipated in these
forward-looking statements. Factors that may cause such differences include
the risk that products that appeared promising in early research and
clinical trials do not demonstrate safety or efficacy in larger-scale
clinical trials, the risk that the Company will not obtain approval to
market its products, the risk that clinical trials may not commence when
planned, and the risks associated with the dependence upon collaborative
partners. These factors and others are more fully discussed in the Company's
periodic reports and other filings with the Securities and Exchange
Commission.
Note: Ceplene(TM), MaxDerm(TM) and the Maxim logo are trademarks of the
Company.
Editor's Note: This release is also available on the Internet at
http://www.maxim.com.
--------------------------------------------------------------------------------
Contact:
Maxim Pharmaceuticals, San Diego
Larry G. Stambaugh, 858/453-4040
Chairman, President and CEO
or
Burns McClellan (Investors)
John Nugent, 212/213-0006
or
Coffin Communications Group (Media)
Sean Collins/Valerie Bent, 818/789-0100
Roche's Pegasys launch unaffected by Weston snagWednesday September 4, 6:59
am ET LONDON, Sept 4 (Reuters) - Switzerland's Roche Holding AG (ROCZg.VX)
said on Wednesday the launch of its new hepatitis C drug Pegasys would not
be affected by problems at needle-free injection specialist Weston Group
Medical Plc (London:WMG.L - News). Shares in the British firm crashed 87
percent on Tuesday after it delayed the launch of its flagship Intraject
device due to design problems. Weston Medical has agreements with a number
of drug companies, including Roche, that are interested in using in
Intraject -- but Roche stressed it was not reliant on the device. "The delay
with Weston Medical's Intraject device does not in any way, shape or form
impact the timely launch of Pegasys in the U.S. or anywhere else," it said
in a statement. The drug will be made available initially in conventional
pre-filled syringes and vials. "Roche has a collaborative agreement with
Weston Medical that would allow Roche to use its Intraject technology once
this technology has resulted in a reliable device," the firm added. The need
for design modifications means the Intraject device will not now be ready
for launch before mid-2005. Pegasys is the Swiss group's biggest new drug
hope. It expects to win U.S. regulatory approval by the end of the year for
the product's use both as mono-therapy and in combination with ribavirin .
U.S. biotech firm Ribapharm Inc (NYSE:RNA - News) is attempting to block the
combination application and has filed a lawsuit to prevent Roche from
selling a competitor to its ribavirin product in the U.S. But Roche insists
it has every right to sell its own form of the medicine.
SciClone Pharmaceutical
To Test Combination Of Unapproved Drugs
Wednesday September 4, 1:42 pm ET
By Christopher Scinta, Of DOW JONES NEWSWIRES
WASHINGTON -(Dow Jones)- SciClone Pharmaceuticals Inc. (NasdaqNM:SCLN -
News) said it will save about $20 million through a deal struck with Swiss
drug giant Roche AG , which will provide its Pegasys interferon free of
charge for clinical trials with SciClone's Zadaxin immune system enhancer to
treat the hepatitis C virus.
But SciClone now finds itself in an odd spot because it enrolled patients
for a trial to test its Zadaxin as a combination therapy with Pegasys
pegylated interferon, although neither has been approved by the Food and
Drug Administration.
SciClone has warned in filings with the Securities and Exchange
Commission that if Pegasys isn't approved by the FDA, the company would need
to repeat the Zadaxin HCV trial with an approved interferon, causing delays
and increased expenses. The company is conducting a phase 3 trial in the
U.S. of Zadaxin to boost the effects of interferon in patients with the
hepatitis C virus, or HCV, who previously didn't respond to interferon
therapy.
HCV is a chronic infection that attacks the liver. The pegylated form of
interferon remains in the body longer, cutting down the number of doses.
A Roche spokeswoman said the company would provide Pegasys for the trial
at no charge to SciClone if SciClone shares its trial data with Roche.
SciClone Chief Financial Officer Rick Waldron told Dow Jones Newswires
the company will test Zadaxin in 1,000 patients it plans to enroll in a
multi- center, placebo-controlled trial for HCV.
"Using two unapproved drugs is rare but the FDA cleared (the trial),"
Waldron said.
An FDA spokeswoman said it isn't unheard of for the agency to allow
trials of a combination of two unapproved products as long as the company
has sufficient data from preclinical tests showing the drugs are safe.
Under FDA rules, even if two drugs weren't approved on an individual
basis, they could be packaged together and sold as one therapy if the agency
found the drugs were safe and effective and approved them in combination.
Minor Risks Exist
In July, the FDA gave priority review designation to Pegasys in
combination with ribavirin for the treatment of HCV and Roche has said it
expects U.S. approval by the end of the year for the drug. But recently no
marketing application has been a sure bet with the FDA.
Waldron said he expects approval of Pegasys by the end of the year, and
though there is a small risk that Pegasys wouldn't be approved, it still is
a risk, so SciClone had to include it in its filings with the SEC.
Pegasys was approved in June by the European Union. Waldron said Zadaxin
is already approved in 28 countries, mostly developing countries, and
generated about $14 million in sales during 2001, mainly for the treatment
of hepatitis B.
H.C. Wainwright analyst Ron Opel said it is difficult to gauge the risk
from the Roche deal because he doesn't follow Roche and has no insight on
the odds for approval of Pegasys, but he said he has heard from Pegasys
users who found the product superior to Schering-Plough Corp.'s PEG-Intron,
a pegylated interferon that already has FDA approval.
It is important for SciClone to break into the U.S. market with Zadaxin,
Opel said, because the level of third-party reimbursement in the U.S. offers
a much greater market opportunity than SciClone has found so far in places
like China.
The analyst rated the company a speculative buy, stating that buy is the
firm's second-highest rating, but SciClone is considered speculative because
of its small market capitalization. Opel's firm did investment banking for
SciClone more than two years ago.
Multiple Drugs A More Common Approach
Using multiple drugs to treat disease has become more common in recent
years, particularly since the success of using drug cocktails to treat
HIV/AIDS. Currently, HCV patients usually get a combination of interferon
and ribavirin.
Schering-Plough currently sells PEG-Intron in combination with Rebetol, a
ribavirin licensed from Ribapharm Inc. (NYSE:RNA - News) , for HCV
treatment.
Aside from its collaboration with SciClone, Roche is seeking approval of
Pegasys for the treatment of HCV in combination with its own version of
ribavirin, though Ribapharm recently sued Roche in the U.S. and Europe
alleging infringement of its ribavirin patent.
Schering-Plough's sales of Intron/Ribavirin products, which are mainly
used for HCV, totaled $659 million for the quarter ended June 30, according
to a company filing with the SEC.
Waldron said SciClone originally planned to test Zadaxin with alpha
interferon but waited until the company could get access to longer lasting
pegylated interferon. The company was concerned pegylated products would
take over the HCV market and feared it would get approval for Zadaxin in
combination with something patients no longer used.
Though SciClone spoke to Schering-Plough as well as Roche, Roche's offer
was difficult to refuse from a business standpoint, Waldron said. Due in
part to the deal, as well as the revenue from foreign sales, SciClone didn't
need to partner with a larger company to fund the trials and so expects to
keep a larger percentage of any Zadaxin revenue.
Ironically, Zadaxin was originally developed at Roche. However, Roche was
also developing interferon at the time and put off Zadaxin, Waldron said.
SciClone eventually acquired all the rights to the drug for about $3.2
million in 1998, according to SEC filings.
Waldron said Zadaxin works in several ways to boost the immune system
against HCV. The injectable product, a manufactured version of a naturally
occurring substance, helps stem cells differentiate into virus-fighting
immune system cells. The drug also helps ease potential side effects by
working to prevent the immune system from fighting the effects of interferon
therapy.
SciClone's trial, which started patient enrollment in April, is planned
for 500 patients with HCV but no liver cirrhosis and 500 HCV patients with
some cirrhosis. It will take about two years to complete the trial and
organize the data for regulatory filings with the FDA.
A Roche spokeswoman said the company could benefit from a Zadaxin
approval but doesn't get any rights to Zadaxin through its deal with
SciClone.
Waldron said other HCV treatments are needed on the market as interferon
and ribavirin combinations only work for about 30% of HCV patients with the
highest viral loads - those with the highest number of virus copies in their
blood. SciClone is focusing its Zadaxin testing on this group.
SciClone has yet to partner with a big drug maker, but it will need to
establish some kind of partnership because of the size of the HCV market,
Waldron said. SciClone plans to see what results the clinical trials yield
before it gets into any partnering discussions.
-By Christopher Scinta, Dow Jones Newswires; 202-628-7699;
chris.scinta@dowjones.com
Oklahoma Hospital Nurse Reused
Needles on Patients
Thu Sep 12, 5:35 PM ET
NORMAN (Reuters) - Six people contracted hepatitis at an Oklahoma
hospital and about 350 other patients were undergoing tests after a nurse at
the facility reused hypodermic needles, a hospital spokesman said on
Wednesday.
Six patients at Norman Regional Hospital, near Oklahoma City, became
infected with hepatitis C virus from the tainted needles, he said.
Officials said nurse-anesthetist James C. Hill admitted reusing needles
while injecting pain medication in patients, from December 31, 2001 through
August 19 of this year.
"We have seen approximately 350 individuals who could possibly have been
exposed," hospital spokesman Grant Farrimond said. "The hospital has
contacted those individuals and offered to test them at their convenience."
About 200 have been tested so far, he added.
Farrimond said that in addition to hepatitis C and B testing, exposed
patients were also being tested for HIV ( news - web sites) infection.
Hill and his supervising physician have been removed from the hospital
and their privileges have been revoked, Farrimond noted.
A lawsuit was filed in Norman on Wednesday against Hill and the
supervising physician Dr. Jerry W. Lewis, by a patient who received
injections at the clinic.
The hospital said Hill used the same needle for at least 15 patients a
day, but would not speculate why he reused needles. The lawsuit is charging
the nurse with negligent and malicious behavior.
Farrimond said the pain clinic, which operated in the hospital, was
privately staffed and operated by Lewis.
GenOdyssee Announces Positive Results of Proprietary Interferon-alpha
Variants for the Treatment of Hepatitis C and Cancer
- In Preclinical Disease Models Variants Demonstrate Increased Efficacy
Compared to Those Currently Available on the Market -
Paris, France, September 5, 2002 - GenOdyssee S.A.,
a biotherapeutics company specializing in discovering and developing
drugs from functional genomics, today announced preclinical results for
its proprietary interferon (IFN) alpha variants for the treatment of
hepatitis C (HCV) and cancer. In the studies conducted by independent
French laboratories, GenOdyssee's variants demonstrated up to one
hundred times greater efficacy compared to IFN alpha molecules currently
on the market.
Professor Michael TOVEY, Director of the Viral Oncology Laboratory at
CNRS Research Institute (French National Center for Scientific Research)
commented, "GenOdyssee's interferons display excellent toxicity profiles
and are much more specific and active than interferons 2a and 2b that
are currently on the market for HCV and cancer. Such a significant
improvement could herald a major advancement in patient treatment for
both conditions. Undoubtedly, GenOdyssee's unique approach has
significantly contributed to our understanding of the underlying
mechanisms behind interferon activity, which are currently not well
documented."
The studies compared GenOdyssee's nine IFN alpha variants to the
currently marketed IFN alpha 2a and 2b variants in viral infectious
disease models for HCV and immunotherapy models for cancer. Certain IFN
alpha variants demonstrated up to one hundred times greater antiviral,
immunomodulatory and antiproliferative activities than IFN alpha 2a and
2b. Other variants exhibited differential activities, for example,
having greater antiproliferative but reduced antiviral and
immunomodulatory properties. Initial in vivo toxicology studies reveal
few side effects and suggest the company's IFN alpha variants are better
tolerated than those currently on the market. Hence, these variants
could provide a more specific and efficient therapeutic, with reduced
adverse side effects, significantly increasing treatment efficacy. The
company believes that the most potent IFN immunostimulating and
antiproliferative variants will enable the development of novel
immunotherapy treatments for common forms of cancer, including lung,
breast and prostate.
"Genodyssee's variants could act as a stand-alone cancer therapy or
act as an adjunct to therapeutic vaccines, providing greater efficacy
than currently available treatments; they make promising candidates for
the treatment of cancer and HCV," commented Professor Hervé FRIDMAN,
from the Paris Pierre & Marie Curie Medical School and Director of
INSERM (French institute for Health and Medical research) unit 255.
Professor Patrick MAUREL, director of INSERM unit 128, who coordinated
the in vitro preclinical studies on hepatocyte culture, confirmed that "GenOdyssee's
variants, showing unprecedented activity on human hepatocyte HCV
infection, make very promising candidates to significantly improve HCV
treatment."
"With these promising results in hand, GenOdyssee now has a proof of
concept for our innovative approach to drug discovery and development.
By combining our expertise in genetic variability with our understanding
of proteins, we hope to be able to select naturally occurring variants
of existing therapeutic proteins which demonstrate a higher therapeutic
index and fewer side effects," said Dr. Jean-Louis Escary, GenOdyssee's
Founder, President & Chief Executive Officer. "The exciting results
from the studies of our IFN alpha variants should enable GenOdyssee to
start clinical development of the most promising variants in both
hepatitis C and cancer in 2003. The HCV market is currently valued at
more than $2 billion, with ten percent annual growth, and the cancer
therapeutic vaccines and direct immunotherapy markets are estimated at
several hundred million US dollars. Hence, given the poor efficacy and
high toxicity of current treatments, our proprietary IFN alpha variants
represent exceptional commercial opportunities." |
http://www.nrp-euro.com/news/view_newsitem.aspx?ItemID=236
|
Updated Listings for Patients Studies and Trials
In order to get further information, you must go to the below url. This
has
been updated at the end of August :) and listings are in the US as well
as
International.
http://www.centerwatch.com/patient/studies/cat79.html |
Roche's ribavirin Copegus
available in all EU Countries within months
Hepatitis C drug completes Mutual Recognition Procedure in the European
Union
Roche announced today that it had received confirmation that the Mutual
Recognition Procedure has been completed for its proprietary ribavirin,
Copegus. This important milestone means that all EU member states have
agreed to approve Copegus for the treatment of chronic hepatitis C in
combination with interferon alfa-2a (Roferon A) or peginterferon alfa-2a (40
KD) (Pegasys).
"Today's approval of our stand-alone application means that we have
satisfied all European Union member states of the safety and efficacy of the
Copegus/ Pegasys combination treatment in patients infected with the
hepatitis C virus ," said William M. Burns, head of the pharmaceutical
division at Roche, adding that "this paves the way for the commercial
availability of Copegus in all EU countries within one to three months. This
is very important news as combination therapies are now standard for the
treatment of hepatitis C."
The Dutch Medicines Evaluation Board, as the EU Reference Member State,
first approved Copegus on April 9th which started this two-step approval
process. National approvals will follow swiftly as Copegus is now an
approved drug. Copegus is manufactured by Roche as a light pink, oval
shaped, film-coated tablet containing 200 mg of ribavirin.
Copegus is indicated for the treatment of adult patients with chronic
hepatitis C who have not previously been treated, including patients with
fibrosis or compensated cirrhosis. It is also indicated for the treatment of
adult patients who have responded to interferon alpha monotherapy but have
since relapsed. Copegus is always prescribed as a combination regimen with
interferon alfa-2a (Roferon A) or peginterferon alfa-2a (40 KD) (Pegasys).
About Pegasys
Pegasys, a new generation hepatitis C therapy that is different by design,
provides significant benefit over conventional interferon therapy in
patients infected with HCV of all genotypes. The benefits of Pegasys are
derived from its new generation large 40 kilodalton branched-chain
polyethylene glycol (PEG) construction, which allows for true seven-day
viral suppression and is preferentially distributed to the liver, the
primary site of infection. Pegasys is administered once weekly in an
easy-to-use pre-filled syringe with a fixed 180 mcg starting dose for all
patient types.
Pegasys has now been approved in 47 countries, including the European Union.
In the EU, it is indicated for the treatment of histologically proven
chronic hepatitis C in adult patients, including patients with early stage
cirrhosis. It is approved both as a combination therapy with ribavirin and
as monotherapy. In the United States, Pegasys in combination with Copegus
was granted a priority review by the FDA and its approval is anticipated
later this year.
About Hepatitis C
Hepatitis C is a serious blood-born viral infection that attacks the liver,
and in many patients it leads to liver disease, cirrhosis and cancer. It is
the leading cause of liver transplantation. Only identified in 1989, the HCV
virus has infected more than 170 million people world-wide, making it more
common than the HIV virus.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading
research-orientated healthcare groups. The company's two core businesses in
pharmaceuticals and diagnostics provide innovative products and services,
that address prevention, diagnosis and treatment of diseases, thus enhancing
people's health and quality of life. The two core businesses achieved a
turnover of 13,1 billion Swiss Francs in the 1st half of 2002 and employed
about 57'000 employees worldwide.
Roche is committed to the viral hepatitis disease area, having introduced
Roferon-A for hepatitis C, followed by Pegasys in hepatitis C, with studies
currently being conducted on its efficacy in hepatitis B. Roche also
manufactures The COBAS AMPLICORä HCV Test, v2.0 and the AMPLICOR HCV
MONITORä Test, v2.0 - two tests used to detect the presence of, and
quantify, HCV RNA in a person's blood. Roche's commitment to hepatitis has
been further reinforced by the in-licensing of Levovirin, an alternative
antiviral. Levovirin will be studied with the objective of demonstrating
superior tolerability over the current standard, ribavirin.
All trademarks used or mentioned in this release are legally protected.
Your IR contacts:
Dr. Karl Mahler Dr. Mathias Dick Dianne Young
Tel: +41 (61) 687 85 03 Tel: +41 (61) 688 80 27 Tel: +41 (61) 688 93 56
email:
karl.mahler@roche.com email:
mathias.dick@roche.com
email:
dianne.young@roche.com
US investors please contact:
Richard Simpson
Tel: +41 (61) 688 48 66
email:
richard.simpson@roche.com
With best regards,
Your Roche Investor Relations Team
F. Hoffmann-La Roche Ltd
Investor Relations
Grenzacherstrasse 68 / Postfach
4070 Basel
http://ir.roche.com/
email:
investor.relations@roche.com
phone: ++41 61 688 88 80
fax: ++41 61 691 00 14
Deaths of Hepatitis C
Patients in Japan Prompt Label Change in Rebetol
Precautionary labeling will be added to Rebetol capsules in Japan about the
risks of using it to treat hepatitis C in patients who also have diabetes
and hypertension after two Japanese patients using the drug together with
interferon recently died.
Schering-Plough distributes Rebetol capsules in addition to its
interferon drug known as Intron A. Both drugs are used together to treat
hepatitis C. Intron A already bears precautionary language in Japan against
its use in hepatitis C patients with diabetes and/or hypertension.
"Essentially, there have been reports of four cases of cerebral
hemorrhages leading to two deaths of patients taking interferon A and
ribavirin in Japan," Schering-Plough spokesman Robert Consalvo told Medical
Week. "All four patients had a history of hypertension. Two patients who
died also had diabetes."
Although uncertain about why the deaths occurred, Consalvo said the
deaths in Japan should not be a cause of concern for people who use the
drugs in the United States since no deaths or adverse events have been
reported here. As a result, he said no plans exist to change the drug's
label in the United State or in Europe.
"Intron A has been on the market here since the 1980s," said Consalvo,
noting that adverse events of such magnitude were not seen in the studies
that supported approval of the drug either alone or in combination with
Rebetol. "These are new cases and the Japanese authorities felt it was
important to add this harmonized labeling," he added.
Consalvo said the new labeling makes it clearer "that you need to take
precautions in patients with these conflicting conditions." He said the
treatment environment that exists in Japan for this combination therapy is
very different in Japan than in the United States or Europe.
In Japan, Consalvo said Rebetol and Intron A are only supposed to be
administered to hepatitis C patients while they are in hospitals. He also
noted that Intron A is given to hepatitis C patients in significantly higher
doses in Japan than in the United States or Eurspark1the use of Intron A
with Rebetol was just launched in Japan late last year.
Other sources: Schering-Plough
HIV Meds May Carry Small Risk
of Heart Arrhythmias
Mon Sep 16, 5:43 PM ET
By Anthony J. Brown, MD
NEW YORK (Reuters Health) - Recent reports have suggested that certain
types of anti-HIV ( news - web sites) drugs can cause abnormal heart
rhythms, or arrhythmias, but if this is indeed true, the risk appears to be
incredibly low, according to infectious disease experts.
The reports have concerned protease inhibitors, an essential component of
the drug cocktail used to fight HIV infection. While prescribing information
for these drugs warns that they can cause arrhythmias when given with
certain other drugs, it is unclear whether protease inhibitors can cause
such disturbances on their own.
Three years ago, Drs. Paul E. Sax and Raphael J. Landovitz of Brigham and
Women's Hospital in Boston, Massachusetts published a case report suggesting
a link between use of nelfinavir (Viracept) and the development of an
arrhythmia.
The case involved a 45-year-old HIV-infected man who was switched from a
regimen containing indinavir to one containing nelfinavir. Twelve hours
after changing to the new regimen, the patient began experiencing
palpitations and testing revealed a type of abnormal heart rhythm called
bradycardia. The patient had no personal or family history of cardiac
problems, including arrhythmias.
After stopping all antiretroviral drugs, the rhythm disturbance resolved.
But when the patient was given nelfinavir alone a few weeks later, the
arrhythmia returned immediately.
"I am convinced, without a doubt, that nelfinavir caused the patient's
bradycardia," Sax told Reuters Health. "Since then, however, I have seen no
other cases of arrhythmia possibly related to protease inhibitor use; and I
work at a center that sees a lot of HIV-infected patients," he added.
Sax noted that he had heard anecdotal reports of protease
inhibitor-related arrhythmias from other physicians, but acknowledged that
the risk of such rhythm disturbances with these drugs is probably extremely
low.
More recently, Dr. Shinichi Oka from the International Medical Center of
Japan in Tokyo and colleagues reported two cases of serious arrhythmias
possibly related to use of lopinavir-ritonavir. Both patients had hemophilia
and were also infected with hepatitis C virus (HCV), the authors note.
Shortly after starting lopinavir-ritonavir for the first time,
arrhythmias were observed in both patients. The rhythm disturbances resolved
after lopinavir-ritonavir was discontinued. When one patient was given
lopinavir-ritonavir several days later, the arrhythmia returned.
"After submitting our paper, we have (encountered) another two patients
who were treated with lopinavir-ritonavir and had bradycardia," Oka told
Reuters Health.
It is unclear if lopinavir-ritonavir actually caused these arrhythmias,
according to Dr. Scott Brun, a researcher for Abbott Park, Illinois-based
Abbott Laboratories, which produces the drug under the trade name Kaletra.
"There were a number of confounding factors that may explain the
association," Scott told Reuters Health. "HCV infection can affect cardiac
conduction and the patients were on a number of concomitant medications that
may have played a role," he added. Also, he noted, levels of certain
immune-system cells were very low, suggesting that the patients might have
HIV-related heart damage.
After becoming aware of the case reports, "we reviewed our data of more
than 10,000 patients treated with Kaletra and we were unable to identify any
patients who experienced serious bradyarrhythmias," Scott stated.
While protease inhibitors appear to have little or no rhythm
disturbance-producing effect, recent findings suggest that they do affect
cardiac anatomy and dynamics.
In a study reported in July, researchers from Johns Hopkins University in
Baltimore used echocardiography to assess the cardiac structure and function
of HIV-infected patients treated with or without protease inhibitors. The
findings suggest that use of the drugs is associated with certain changes in
the heart's structure and function.
Lead researcher Dr. Shenghan Lai told Reuters Health that his group is
planning a study with MRI scans to further investigate the drugs' effects.
In the meantime, he recommends that patients taking protease inhibitors be
evaluated with echocardiography, an ultrasound scan of the heart, every 6
months.
|
Pegasys + Ribavirin: study results
published 
