AIDS TREATMENT NEWS #137, October 18, 1991
Denny Smith

The drug's developer, Abbott Laboratories, has established an open-label trial intended to create "expanded access" for physicians treating patients with MAC. But that program has come under the scrutiny of physicians and activists recently for extraordinarily stringent entry criteria and monitoring requirements.

Last August 20, the Community Consortium, an association of San Francisco Bay Area HIV physicians, sent a letter to Abbott asserting that troublesome entry criteria and laboratory processing for the clarithromycin protocol are not translating into truly "expanded" access.

Among the complaints leveled against the protocol is that its stipulations resemble those of a full-fledged controlled clinical trial, but that it is not funded as such by the developer; a protocol which would not be considered burdensome within the context of a multi-center controlled study with adequate support services is instead falling on the shoulders of busy, individual doctors. The implication emerged that Abbott is collecting the benefits of large-scale trials while avoiding the expense.

Another problem is the requirement that potential participants, even as their blood cultures prove they have MAC, must discontinue other MAC drugs for one month before receiving clarithromycin. The Consortium letter called this "clinically unjustifiable." In the end, those patients needing a new option the most may become the least eligible under Abbot's protocol. Other problems, which may have been partly addressed by Abbott since the letter was sent, include the requirement of multiple processing of lab specimens and proof of disseminated MAC.

On September 10, Abbott responded to the Consortium with a brief letter, saying essentially that the protocol's design was warranted and would not be changed. Abbott acknowledged that some of the requirements "are more cumbersome than that of other compassionate programs," and that "there is presently a substantial use of clarithromycin obtained through illegal sources and that patients are taking as little as 250 mg twice a day, which may be an insufficient dose and result in the development of resistant organisms and leave patients with no alternative treatment ..."

(Comment: If Abbott is referring to the importation of clarithromycin from abroad, then the choice of the phrase "illegal sources" is inaccurate. Americans are not transgressing FDA limits when they acquire, for personal use, drugs approved in other countries. If Abbott is genuinely concerned about collecting sufficient data to establish safe and efficacious doses for clarithromycin, then what is warranted is a protocol that streamlines the responsibilities of the physician petitioning for the drug, thus optimizing the number of participating patients, and eliminating their need to pursue other avenues of access).

Abbott has been pursuing FDA approval for clarithromycin to treat certain non-life-threatening skin and respiratory infections. Theoretically, the company might save enormous amounts of money by skipping the studies needed to prove to the FDA that the drug is also effective against MAC, toxoplasmosis or cryptosporidiosis. Early approval of clarithromycin for any indication would automatically make it available for physicians treating AIDS-associated infections. But unfortunately, health insurers, public and private alike, are eager to deny payment for any treatment unless specifically indicated in the product labeling.

In other words, clarithromycin could remain virtually out of reach for most people, whether or not it wins FDA approval.

On the positive side, some of the other charges leveled against Abbott's program may have been answered. The original protocol called for proof that the MAC infection was disseminated. On October 17 Gordon Nary of the Physicians Association for AIDS Care (PAAC) in Chicago told us that after some negotiating, Abbott has agreed to accept a positive culture that has tentatively ruled out tuberculosis -- allowing for a presumption of the dissemination. A procedural detail regarding Institutional Review Boards was also loosened.

The original protocol also disallowed anyone who had tried the drug already, meaning, of course, the many people who have spent considerable money buying imported clarithromycin from Europe. Under pressure from ACT UP and Project Inform, Abbott has created an additional protocol which will admit those who have had prior experience with the drug. Michael Wright of Project Inform met personally with Abbott representatives, and told us that about 500 patients had been enrolled under the first protocol, and about 100 are enrolled in the new one. He said that even if Abbott's drug is approved for lesser infections, he expects the company to continue studies toward AIDS-related indications. Michael is willing to field calls from people who are still having a difficult time with Abbott's clarithromycin protocols. Messages can be left for him at the Project Inform hotline (for hours and phone numbers, see the Project Inform announcement, below, on page 8 of this newsletter).

Meanwhile, Abbott is expected to begin trials of the drug as a prophylaxis against MAC by January 1. The question remaining is when clarithromycin will be tested in combination with other MAC drugs to treat active MAC infections. Most researchers and clinicians we've spoken to think that this infection will not optimally respond to single-drug treatment.

The number at Abbott to call for clarithromycin information is 800/688-9118, 9 a.m.to 9 p.m. Eastern time.

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