[NYTr] Low-Key Recall of AIDS Drug Hits World's Poor

[nytr at olm.blythe-systems.com]

The New York Times - July 23, 2007
http://www.nytimes.com/2007/07/23/health/23recall.html


Low-Key Recall of AIDS Drug Hits World's Poor

By Elisabeth Rosenthal

ROME--A total recall of an important AIDS drug widely used in
developing countries has disrupted treatment for tens of thousands of
the world's poorest patients, with no clear word from the manufacturer
on when shipments will resume.

The recall of the drug, Viracept, by Roche Pharmaceuticals of
Switzerland, went largely unnoticed in the developed world when it was
announced in early June, after the company had discovered that some
batches made at its Swiss plant contained a dangerous chemical. But the
recall has caused growing concern among global health officials and in
AIDS programs in many poor nations. They say the company did an
inadequate job of informing patients and officials about the potential
risks and helping them find affordable access to newer alternative
drugs.

Roche said that it had been actively working with health officials
across the globe and that the risk from the affected batches was low.

The scope of Roche's recall is extraordinary, if not unprecedented, in
the battle against the human immunodeficiency virus that causes AIDS,
global health officials say. Dr. Lembit Rago, an official at the World
Health Organization, said tens of thousands of people take Viracept
worldwide, many of them poor people with H.I.V. in developing
countries. The recall has left those patients with the painful choice
of discontinuing a lifesaving medicine, or using a drug that might
contain a dangerous contaminant.

Officials at the W.H.O. in Geneva and the European Medicines Agency in
London said Roche had not provided information they consider essential
for safeguarding public health: which countries the tainted medicine
was shipped to, the concentration of the contaminant and what the
company will do for its patients. The European agency, which regulates
drugs for the European Union, has canceled Roche's license to market
the drug.

Dr. Rago called the recall "sort of a disaster" for patients in very
poor countries. He said of Roche, "They failed in communication." Roche
has denied the accusation. The company, which had revenue of $35
billion last year, said it promptly notified health providers in the
affected countries to discontinue use of the drug, which is dispensed
in both pill and powder form. It also said it would cover the
"reasonable costs" of the recall. It did not define "reasonable costs."

So far, in some countries like Panama, patients or treatment programs
have had to make up the difference in cost between Viracept and far
more expensive alternatives. For some patients in other countries, like
Venezuela, alternatives to Viracept are unavailable.

Roche said the recall affected "Europe and some other world regions"
but has not been more specific. The recall does not affect the United
States, Canada or Japan, where a version of Viracept is made by Pfizer.
Roche has been in discussions with Pfizer about supplying Pfizer's
version to some affected countries, but regulatory and licensing issues
could take "some time," said Martina Rupp, a Roche spokeswoman.

Roche sells Viracept for use in low-income countries at the discounted
median price of about 28 cents a dose, according to the W.H.O.'s 2006
global price reporting system for AIDS medicine. The drug, also known
as nelfinavir, is a member of the class of AIDS drugs known as protease
inhibitors. It is considered an important defense against H.I.V., but
it has fallen out of favor in Europe in recent years compared with
newer medicines that are more convenient and cause fewer side effects.

In some places, newer substitutes are not available to patients, either
because they are not licensed or are much more expensive, said people
with H.I.V. and international health experts. In Panama, for example, a
substitute drug, Kaletra, costs three times as much as Viracept.

"Roche has provided information, but there has been much less support
in terms of who is going to pay the additional cost," said Dr. César
Nuñez, the United Nations AIDS program's coordinator for Latin America,
who is based in Panama.

A more limited recall might have been possible had Roche been more
forthcoming about the countries affected and the lots that were
suspect, said Dr. Rago, the W.H.O. coordinator of quality assurance and
safety for medicines. "It's fine for Roche to say 'withdraw and
replace,' but there may not be much else at hand to substitute" in many
places, he said. "This is not just about Europe."

In response to questions sent by e-mail, Ms. Rupp said Roche had
shipped "at least one packet of Viracept with high levels of the
impurity to 35 countries." But she declined to say which countries
because Roche regards such information as proprietary. High levels of
the contaminant "were observed in batches of Viracept that had been
released to countries since March 2007," she said.

The company made the recall worldwide "in order to avoid confusion,"
she said. Roche estimates that about 45,000 patients were affected by
the recall. Ms. Rupp said the toxic substance, ethyl mesylate, should
be called an "impurity" rather than a contaminant because it was
created in the manufacturing process and because that type of chemical
can be found in very low levels in other medicines, although it was not
supposed to be present in Viracept.

The company was performing studies on the issue, but the results would
not be available for "some months," she said. At high doses, ethyl
mesylate has been shown to cause cancer in animals, and at lower levels
it can cause genetic mutations, which means children and fetuses are
particularly vulnerable.

Asia Russell, the coordinator of international advocacy for Health Gap,
a nongovernmental organization based in New York and Philadelphia that
focuses on medical care in the developing world, said, "It seems that
Roche has abandoned these patients, since in many places there aren't
ready alternatives."

In Venezuela, 3,000 people were on Viracept, paid for by the national
health service, and the effect of the recall was "severe," because many
had no other options, said Edgar Carrasco, an advocate on issues
relating to AIDS in Caracas.

Alberto Nieve, another advocate, said Roche had promised to make a
donation of another medicine. "Most people are still waiting," he said.
"They have not switched yet, especially outside Caracas."

In the month since the recall, officials at the European Medicines
Agency and the W.H.O. said that they, too, would like more information
from Roche about the dose of the contaminant and where exactly the
medicine was sent.

"We have not gotten information, not even an order of magnitude," said
Martin Harvey-Allchurch, a spokesman for the European agency. "I
understand sales figures are confidential, but I would have thought by
now we would have this information."

Viracept was sold in 49 countries since 2004, according to the W.H.O.,
with more than 12 million units sold in 2006 and 2 million in 2007.
Tido Von Schoen-Angerer, director of the essential medicines campaign
at Doctors Without Borders, said about half of the 400 patients who
received therapy supplied by the group in Africa were on Viracept. The
alternate from Abbott is not yet available, he said.