AEGiS-PRn: Sarawak MediChem Pharmaceuticals Begins Phase 1B Clinical Trial of Plant-Based Anti-HIV Agent

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Sarawak MediChem Pharmaceuticals Begins Phase 1B Clinical Trial of Plant-Based Anti-HIV Agent

PRNewswire - Wednesday September 30, 1998

LEMONT, Ill., Sept. 30 /PRNewswire/ -- Sarawak MediChem Pharmaceuticals, Inc., has begun screening volunteers for a 32-patient Phase 1B clinical trial of (+)-calanolide A, an anti-AIDS compound discovered in the rain forest of Sarawak, Malaysia. The six-month trial will be performed at six research centers in the United States and will evaluate the safety, pharmacokinetics and effects of two doses of (+)-calanolide A on surrogate markers in HIV-positive patients with no previous antiretroviral therapy. It will be a randomized, sequential, double-blind, placebo-controlled study.

As well as assessing safety and pharmacokinetics, Sarawak MediChem researchers intend to evaluate the effect of (+)-calanolide A on viral load and viral resistance, and compare the effect of the treatment on changes from baseline CD4+ cell count (see note).

After treatment, subjects who participate in the trial may elect to receive an open-label, six-month course of approved anti-HIV drugs to be selected by and administered under the care of the subject's physician.

Results of a Phase 1A trial with healthy volunteers, who received escalating single doses or multiple doses, showed (+)-calanolide A to be well-tolerated. It was absorbed and circulated in the bloodstream, resulting in higher blood concentrations than anticipated from animal data. The most frequent adverse effects were dizziness, oily aftertaste, headache, belching and nausea, which were mild to moderate. Pharmacokinetic analyses suggest once or twice daily dosing.

(+)-Calanolide A was isolated from the bintangor tree (Calophyllum lanigerum) by the National Cancer Institute (NCI), after a team of botanists from the University of Illinois and the Arnold Arboretum, under the auspices of the NCI, collected plant samples from the Malaysian rain forest. With the plant source proving to be rare, MediChem Research, Inc., synthesized the compound.

In vitro studies have shown (+)-calanolide A, a non-nucleoside reverse transcriptase inhibitor (NNRTI), to be active against HIV-1, including strains resistant to AZT, Nevirapine and other NNRTIs. It has also exhibited synergistic anti-HIV activity when used in combination in vitro with nucleoside analogs such as AZT, ddC, ddI, d4T and 3TC; with non-nucleoside inhibitors such as Nevirapine; and with protease inhibitors such as Saquinavir and Nelfinavir.

Animal studies have shown the compound to penetrate into viral reservoir sites by crossing the blood-brain barrier into the brain and accumulating in the lymph nodes.

Sarawak MediChem Pharmaceuticals, Inc., is a joint venture between MediChem Research, Inc., and the State of Sarawak, Malaysia, to advance the clinical development of (+)-calanolide A. Formed in 1987, MediChem Research is a privately held biotechnology firm specializing in custom organic synthesis. It holds a patent for the total synthesis of (+)-calanolide A. It also has a worldwide exclusive license to the National Cancer Institute patent on the structure of the compound, as well as to the rights held by the government of Sarawak. For more information, visit MediChem's and Sarawak MediChem Pharmaceuticals' web sites at www.medichem.com and www.sarawak-medichem.com. A non-scientific version of this press release can be made available by calling 708-383-3939.

NOTE: The 4 in CD4+ is a subscript and the + is a superscript.

SOURCE: Sarawak MediChem Pharmaceuticals, Inc.
980930
PR980926

Copyright © 1998 - PRNewswire. All rights reserved. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through PRNewswire, Permissions, 810 Seventh Ave., 32nd Floor, New York, NY 10019 http://www.prnewswire.com.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Elton John AIDS Foundation UK, the National Library of Medicine, AIDS Walk of Orange County, and donations from users like you.

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, 1998. 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. .