Food and Drug Administration, U.S. Department of Health and Human Services - February 16, 1988
Brad Stone (FDA); (301) 443-3285 Elaine Baldwin (NIAID); (301) 496-5717

Trimetrexate is the first AIDS-related drug to be granted treatment IND status under FDA's new regulations. The new treatment protocol will allow NIAID to provide drug therapy to AIDS patients with Pneumocystis carinii pneumonia who experience severe or life-threatening adverse reactions to the conventional approved treatment drugs, trimethoprim/sulfamethoxazole and injectable pentamidine.

FDA's "treatment" IND, or investigational new drug, regulations provide a mechanism for drug developers to provide promising experimental drugs to patients with immediately life-threatening or certain serious conditions before complete data on the drug's efficacy or toxicity are available to enable approval for full commercial distribution. They became effective in June 1987 following the highly successful use of a treatment IND-type mechanism for the early distribution of the drug Retrovir (commonly known as AZT) to some 4,000 AIDS patients in 1986.

"Today's action reaffirms FDA's commitment to broaden early patient access to promising experimental treatments for AIDS, AIDS-associated conditions and other life-threatening diseases," said FDA Commissioner Frank E. Young, M.D., Ph.D. "Thanks to this effort with NIAID, trimetrexate's increased availability to those people with AIDS who could potentially benefit from it brings us another step forward in treating one of the most devastating infections seen in AIDS."

NIAID Director Anthony S. Fauci, M.D., said, "This treatment IND will allow us to offer an important treatment alternative to severely ill patients who cannot tolerate the standard therapy. It is also an example of how NIH is meeting one of its major goals -- enabling community physicians to select the most appropriate therapies for their patients with AIDS."

Trimetrexate is an anti-folate drug, first synthesized in 1969 by scientists with the Warner-Lambert Co. of Morris Plains, N.J.. Developed as an anti-cancer drug, its use as a potential treatment for Pneumocystis carinii pneumonia was proposed by scientists at the National Cancer Institute in the summer of 1985. The protocol for human testing of the drug was filed by NCI with FDA in September 1985 and was granted by the agency later that same month. Following promising data from these trials, NIAID made application for permission to distribute the drug under a treatment IND.

Trimetrexate has been designated as an orphan drug by FDA's Office of Orphan Products Development. This status provides the sponsors of certain drugs for rare diseases with tax and other financial incentives designed to encourage their development efforts.

Since trimetrexate is toxic to the bone marrow cells and gastrointestinal tract, and potentially lethal at the doses needed to treat Pneumocystis carinii pneumonia, it is imperative that it be administered concurrently with leucovorin, an approved drug used for protecting human cells from the harmful effects of anti-folate drugs. In this case, leucovorin acts to protect the patient's cells from injury associated with exposure to trimetrexate. However, careful patient monitoring is essential to fully ensure patient safety under this therapy.

Although there are two approved drugs for the treatment of Pneumocystis carinii pneumonia -- injectable pentamidine and trimethoprim/sulfamethoxazole -- scientists have been interested in trimetrexate because of the possibility that, when used in combination with leucovorin, the treatment may be less toxic than the two approved drugs or may be effective against cases in which adverse reactions to the two approved drugs preclude further effective treatment. Controlled clinical trials sponsored by NIAID have been initiated to address these questions and to evaluate the benefits and risks of trimetrexate in larger numbers of patients.

Under the conditions of the FDA-approved protocol, NIAID will begin distribution of the drugs (trimetrexate and leucovorin) to AIDS patients with Pneumocystis carinii pneumonia who have shown a servere or life-threatening adverse reaction to the approved therapies. Physicians interested in learning about the details of this distribution can contact an NIAID hotline at 1-800-426-7527 within the United States (except in Michigan, where it can be reached at 1-800-833-0014) from 8:00 AM to 8:00 PM, (Eastern Standard Time), Monday through Friday.

880216
FD880201

SOURCE: Food and Drug Administration (FDA).

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1988. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .