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New Company to Advance Calanolide A for AIDS.
MediChem Research, Inc., announced April 25 that the privately held biopharmaceutical firm has entered into a joint venture with the State of Sarawak, Malaysia, to form Sarawak MediChem Pharmaceuticals, Inc.

The new company will advance the clinical development of the anti-HIV compound called Calanolide A, discovered in the Sarawak rain forest. Calanolide A is the only naturally occurring anti-HIV compound known to be at an advanced stage of testing; no anti-HIV drug on the market is a natural product. Pending approvals from the FDA and the results of testing with healthy volunteers, the new company could have preliminary findings of Calanolide A's ability to fight HIV in humans by early 1998. Sarawak MediChem Pharmaceuticals, Inc., began clinical trials of Calanolide A in June and will be on a fast-track schedule. The Phase 1A trial is assessing the safety and human tolerance of the compound in approximately 50 healthy volunteers and is taking place in Tacoma, WA. The Phase IB trial is scheduled to begin February 1998, pending FDA approval. Researchers will study the compound's safety, efficacy, absorption, relative benefit, and synergy with existing treatments in approximately 4 0 HIV-positive volunteers. Phase 1B will likely take place in Chicago. Phases 2/3 could begin in late 1998 and will expand on the investigations of Phases 1A and 1 B, and also include variables such as age, gender, pregnancy, pre-existing conditions and ethnicity. It will involve 100 to 500 patients and will take place in several medical centers across the country. The need for additional study will be determined by the Phase 2/3 findings.

The Calanolides are a group of compounds originally isolated from the Calophyllum lanigerum Miq., Clusiaceae (Guttiferae) tree. A specimen (Burley and Lee 351) was brought to the Arnold Arboretum and, in 1991, an extract from the sample sent to NCI proved to display "100 percent protection against the cytopathic effects of HIV-1 infection and essentially halted HIV-1 replication." These were discovered through the National Cancer Institute's anti-HIV screening program, with Calanolide A found to be active against the virus in 1992.

When botanists returned to Sarawak to collect material from the original plant, they found that the grove had been cut down several years earlier, perhaps by local people for fuel or building material. Samples taken from other specimens of what appeared to be the same species produced only very small amounts of cananolide. A search revealed trees of Calophyllum lanigerum in the Singapore Botanical Garden.

Scientists at the NCI studied Calanolide A, the most potent of the Calanolides, and patented the compound,. MediChem Research then developed and patented a process for synthesizing Calanolide A. In 1995, MediChem was granted a worldwide exclusive license to the NCI patent and to the rights held by the government of Sarawak.

Laboratory tests of Calanolide A conducted by MediChem Research have shown the compound to completely inhibit replication of the AIDS virus. It is active against strains and mutations of the virus that are resistant to AZT and other drugs, and has unique properties that make it more effective in combination with AZT or other anti-HIV agents.

Calanolide A works against the virus differently than most anti-HIV compounds now available. It is a non-nucleoside HIV-1 reverse transcriptase inhibitor (NNRTI), whereas most anti-HIV compounds on the market are protease or nucleoside reverse transcriptase inhibitors. Because it attacks the virus differently than protease and nucleoside reverse transcriptase inhibitors, Calanolide A could prove to be particularly important in the war on AIDS as part of the emerging drug "cocktails" approach.

[Compiled by Barbara A. Johnston from MediChem Research, Inc., press release. April 25, 1997.

Arnold Arboretum Director's Report 1994-1996. 1997.]

Article copyright American Botanical Council.


By Barbara A. Johnston