RIBAVIRIN. PEPTIDE T

Published in SAN FRANCISCO SENTINEL, January 16, 1987. Also published in AIDS TREATMENT NEWS, same date.


Ribavirin News and Confusion

Last week the manufacturer of ribavirin released key results from a double-blind study of that drug's effectiveness in preventing persons with lymphadenopathy syndrome from progressing to AIDS. Although questions remain, the results are good.

Unfortunately much confusion grew from the ribavirin announcement. The extensive media reports have not told what is going on.

The announcement, by ICN Pharmaceuticals of Costa Mesa, CA, at a Washington, DC press conference, essentially consisted of six numbers. Of 56 patients who received a placebo, ten developed AIDS in the 24-week trial. Of 55 who received 600 mg per day of ribavirin, six developed AIDS. Of 52 who received 800 mg, none developed AIDS.

These results raised two questions. First, few physicians believe that the difference between 600 and 800 mg could be as significant as these results suggest; therefore we should not assume that 800 mg dose was completely effective, because it is more likely that the fact nobody at all to AIDS was partly due to lucky chance. Also, the total number who developed AIDS in the first two groups was much higher than would be expected, and no one knows why.

While the scientists' work continues, people must make life and death decisions. There is little doubt that these
results taken as a whole add powerful support to the already powerful case that ribavirin can be an important treatment for some patients. Still, you have to get it in Mexico, and physicians are reluctant to advise you to do so.


Behind the Scenes

Here is some background information we have not seen reported.

* Last-minute change. The January 9 press conference had been planned to announce not only the results above, but also Federal approval of an extended IND (investigational new drug) application. ICN already has an IND for ribavirin, which gave it permission to use the drug in the trials mentioned above. The new IND would have allowed much larger trials, probably with thousands of patients, under a detailed protocol somewhat like the one used for AZT. In fact, the FDA (U.S. Food and Drug Administration) agreed to handle ribavirin like AZT, in order to treat the two manufacturers equally.

But unexpected events days before the press conference prevented final completion and approval of the plan. ICN and the FDA quickly agreed, one day before the press conference, that the company would go ahead with the announcement but release only the principal result at this time.

Unfortunately, the ensuing confusion in the first day's media reports made everyone look bad. ICN appeared to be raising false hopes in order to promote itself, by getting front-page publicity for partial results which left important
questions unanswered. And the widely circulated report in early editions of the January 10 New York Times implied that
both ICN and the FDA were passing the buck; it quoted ICN as saying it had no plans to make ribavirin available until the
FDA approved, and quoted the FDA as saying that ICN had not submitted a formal request for approval. Technically both statements are true, but our well-placed source reports that the agency and the company are in fact working well together, that together they have produced a plan for large-scale distribution which came within a hair's breadth of release on January 9, and that the plan is now under review and likely to be released, possibly in as little as two weeks.

* The ARC study. The results given January 9 concerned only persons with lymphadenopathy. A separate part of the same study tested whether ribavirin could prevent development of AIDS in persons more seriously ill with ARC. These results are expected shortly--along with the release of the plan mentioned above. We have heard that 24 of the ARC patients developed AIDS, but we don't know the breakdown of the 24 into the three treatment groups (placebo, 600 mg, and 800 mg).

* Dosage. Some people believe that 1000 or even 1200 mg would be better than 800, for those persons who can tolerate that much. Apparently almost everyone can tolerate 800; we heard that no one had to be taken off the ICN study due to side effects, and no one needed a transfusion.


Ethical Issues

The gay community and others involved with AIDS must address and clarify certain ethical issues concerning
experimental treatments.

* False hope or false hopelessness? Is it raising false hope to spread good news about promising but as yet unproven treatments? Or is it false hopelessness to teach people to ignore new developments and prepare for death?

The conventional approach is to leave treatments to the experts until they are proven safe and effective and released for marketing. But we should remember that final proof and approval take years even after a drug has proven itself well enough to get many scientists, physicians, and investors behind it.

The other way is to run with every reasonable treatment lead until we know whether or not it works. The risks are
often very small, and in any event they must be balanced against the risks of doing nothing. AIDS has killed perhaps a
thousand times more people as all the experimental treatments put together. And any published results help doctors and scientists develop better treatments in the future. Why give up on all new treatments just because several have been disappointing?

* Publicity and secrecy. Researchers have been criticized when they report results to the press and public, rather than through medical journals or meetings. But it takes months to get published in a medical journal, and during this time most journals insist that the results be kept secret from the press and public, and therefore also from most scientists and physicians. This secrecy enables journals to make a splash in the news when their issues come out, but it has seriously slowed AIDS and other research. This research depends on public interaction among scientists who may be in different lines of work and unable to communicate privately since they do not personally know about many others who are doing work relevant to them.

In recent years the public has shown an unprecedented interest in and demand for detailed medical knowledge. Books like the Physician's Desk Reference have become bestsellers. This trend is part of the growing movement for persons to take more responsibility for their health, instead of leaving it to the experts.

Persons with AIDS and ARC and their physicians must make treatment decisions, including decisions about unapproved treatment options. It is wrong to withhold the information they need.

* Availability. Ribavirin has been sold for human use for 12 years. It is now approved in about 40 countries, including many in Western Europe and elsewhere which have sophisticated drug-testing requirements. For over two years, growing evidence has suggested that this broad-spectrum antiviral might be useful for AIDS.

Now ribavirin has shown good results in a major double-blind placebo trial. Still, U.S. physicians cannot prescribe it, and patients must get it in Mexico. This is inexcusable.

The U.S. drug-approval system reflects the interests and needs of giant pharmaceutical companies far more than the interests and needs of persons with AIDS. Government drug approvals have in fact become corporate assets, like patents, licenses, stocks, and other forms of wealth. This web of vested interests, not concern for patients' welfare, has controlled the regulatory response to the AIDS emergency. Corporations which played by the rules, and earned their drug marketing approvals at the cost of tens of millions of dollars each, would object to the government now giving quick and free summary approvals to their rivals. Consider, for example, the current Federal decision to treat ribavirin and AZT equally, although one has been in routine human use for 12 years while the other is brand new and known to have serious risks. Corporate interests, not patients' interests, came first.

This system will continue to deny medically sound treatments to persons who are seriously ill until medical
associations, patients' organizations, and other public- interest groups start advocating far more forcefully for
patients' rights to treatment, telling Congress, the media, and others that the current system which purports to protect the
welfare of patients is in fact undermining it.

We can start by remembering the third of the Four Moral Appeals of the ARC/AIDS Vigil:

"We appeal to the FDA to immediately allow American physicians to prescribe medicines and treatments for ARC and AIDS that are available to their colleagues in other countries."

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Peptide T

An experimental substance called "peptide T" may represent a major research breakthrough, and it could be available soon for human use.

Peptides are short chains of amino acids (the building blocks of proteins). Peptide T is a chain of eight amino
acids, namely Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr (using conventional three-letter abbreviations). The name came from
the fact that four of the eight amino acids happen to be threonine (abbreviated 'Thr', or 'T').

Scientists discovered the above formula by computer matches of protein sequences in the AIDS virus and elsewhere, and then they synthesized peptide T in the laboratory.

Peptide T seems to be the small piece of the AIDS virus which attaches to a receptor site on the surface of the helper T-cell. The virus must attach to this site in order to infect the cell. Apparently peptide T attaches instead, preventing the virus from doing so.

In laboratory tests, extremely small amounts of peptide T reduced infection of human helper T-cells. Slight variations of the peptide could greatly improve or diminish its effectiveness. The best variant inhibited AIDS virus infection at concentrations of about one part in ten million. The researchers see this result as only the beginning of the
development of a whole new class of treatments for AIDS and other conditions.

Peptide T has already been given to four terminally ill AIDS patients in Sweden; their condition improved and all are still alive. According to the Public Affairs Branch of the Office of Scientific Information, National Institute of Mental
Health (NIMH), the NIMH together with the National Institutes of Health have applied to the U.S. Food and Drug Administration for an IND (approval to use an investigational new drug), and hope to begin human trials very soon. The spokesperson did not know of any funding problems or any other barriers which would prevent the trials from starting as soon as the IND is approved. However, another official at NIMH said that animal toxicity tests would be needed first.

More information about peptide T can be found in the highly technical article published in the December 1986
Proceedings of the National Academy of Sciences. A description appeared in The New York Times, December 16, 1986, page 18.

The public, through its AIDS, medical, and other public- service organizations, must continue to watch the development of peptide T, as well as other treatment research. In the past, too many promising AIDS treatment leads have been strangled in red tape or left on the shelf to collect dust instead of being tested promptly. Only continuing public vigilance can make sure it doesn't happen again.