TCS Daily

Knock It Off

By James K. Glassman - July 11, 2004 12:00 AM

BANGKOK -- A powerful new report, released Sunday at the giant 15th International AIDS Conference here in Thailand, charges that poor-quality drugs, made by dubious manufacturers in countries like Cambodia, could make the AIDS epidemic worse.

The report warned that the flood of these drugs "could lead to widespread misuse and eventually to drug resistance, eradicating years of progress in treatment and prevention of HIV/AIDS" through much of Asia.

Unfortunately, many AIDS activists, as well as such American politicians as Rep. Henry Waxman (D-Calif.), are ignoring the serious warnings -- both from this report and from other health experts -- that churning out untested "copy drugs" and distributing them without proper supervision in poor countries is extremely dangerous.

The report, by the respected American Foundation for AIDS Research (Amfar) in New York, notes that at least 27 Asian companies, as well as one in Africa and four in South America, are making anti-HIV drugs, but only three of those meet benchmark standards set by the World Health Organization.

Even the WHO standards fall far short of those demanded by regulatory agencies in developed countries, such as the FDA.

All of the drugs produced by the 32 companies are copies of anti-retroviral drugs (ARVs), which aim to prevent the human immunodeficiency virus (HIV) from developing into full-blown AIDS.

ARVs were discovered and patented by research pharmaceutical firms in the United States and Europe and have reduced AIDS deaths in the developed world.

Unlike generic drugs in use in the U.S., for example, copycat products have not been certified as equivalent to original patented products. "Substandard AIDS medications can easily be sold to the general population," says the report.

In addition, the Amfar report expresses concern that there are few properly trained health workers to administer treatment with the drugs. "China, the most populous country in the world, has fewer than 200 trained doctors for an estimated 840,000 HIV-infected individuals," says the report.

The lack of health workers is part of a general weakness in health care infrastructure in Asia, "including research, training, and community education" needed to reach a growing HIV-positive population.

"That's a serious concern when you're dealing with drugs that are very toxic," said Kevin Frost, director of Amfar's Treat Asia program. "If patients [lack] proper supervision, it can very quickly lead to drug resistance and side effects, which if they are not managed, can be deadly."

Untested drugs plus inadequate infrastructure are a toxic combination. But that lesson appears lost on Waxman, the top Democrat on the House Government Reform Committee. He sent a letter to HHS Secretary Tommy Thompson on Thursday demanding a further relaxation in reviewing AIDS drugs for use in the developing world.

What Waxman and the activists from groups like Oxfam want is one standard for drugs given to patients in rich countries and another for drugs given to patients in poor countries.

Earlier this year, the U.S. government, which spends more to fight AIDS globally than the governments of the rest of the world combined, said that it would use taxpayer money to buy AIDS drugs for patients in poor countries only if those drugs are ruled safe and effective by the FDA.

Buying unproven drugs, when proven drugs exist, made little sense to Amb. Randall Tobias, who heads the President's Emergency Plan for AIDS Relief, which is committed to spending $15 billion to fight AIDS in 12 African countries, as well as Haiti, Guyana and Vietnam.

In May, the U.S. announced that it would put requests for approval of AIDS drugs made by companies anywhere in the world on a special fast track, with a review completed within "two to six weeks."

That was not good enough for Waxman, who complained in his letter that "the pre-submission process" is burdensome.

Burdensome? The FDA is asking is, for example, that Indian firms that copy U.S. drugs prove that those drugs are safe and effective -- just as U.S. firms must.

But now, two months after the FDA loosened its rules, no maker of ARV copy drugs has submitted medicines for review.

In his letter to Thompson, Rep. Waxman focused on a fixed-dose combination (FDC) drug called Triomune, made by the controversial Indian firm Cipla.

That firm was the subject of an embarrassing decision May 27 by the World Health Organization, which took two of Cipla's ARVs off its list of "pre-qualified" AIDS drugs because the ARVs were not shown to be "bioequivalent" to the two patented drugs of which they were copies.

One of the ARVs -- Lamivudine -- is an ingredient in Triomune, which raises serious concerns about that FDC.

But rather than directing his attention to Triomune's potential dangers -- as he would if Trimoune were a drug being administered to Americans -- Waxman instead lauds a small study of Triomune conducted in Cameroon. That study has been heavily promoted by Doctors Without Borders, an influential non-governmental organization.

The Trimoune study appeared in The Lancet on July 6, on the eve of the conference. But it had severe deficiencies. It was not a clinical trial, as Jerry Norris, a senior fellow at the Hudson Institute, pointed out in a detailed critique. "There was no comparator drug used," he wrote. "There was no control group. While the findings may 'lend' support [a phrase used by The Lancet], therapeutic medicine requires much more stringent and exacting standards,...and they require clinical trials."

In his critique, Norris also noted that, although the Lancet said that no clinical trials had been contacted prior to those in Cameroon, a Scientific Dossier published by Cipla "contains information on their clinical trials conducted in 2002-03" and another large clinical trial in India.

When Norris asked the CEO of Cipla about them, he at first denied they had occurred, then said the trials were "confidential," according to Norris.


TCS Daily Archives