By Lisa Seachrist

Washington Editor

As a result of drug interactions, a Phase III study of Triangle Pharmaceuticals Inc.'s HIV therapy Coactinon (emivirine), formerly known as MKC-442, in combination with a three-drug regimen including protease inhibitors, has been altered to give patients the option of continuing on their regimen or to switch to one that doesn't contain Coactinon.

The study has been unblinded and patients given the option to stop taking Coactinon as a result of an increase in side effects, particularly nausea and dizziness. In addition, patients were showing no additional clinical benefit from the addition of Coactinon to the highly active anti-retroviral therapy regimen.

Triangle's stock dropped 19 percent on the news to close at $15.875, down $3.75 a share.

"We're an event-driven company," said David Barry, chairman and CEO of Durham, N.C.-based Triangle. "And this is not a positive event. We are really looking at this as a bump in the road."

The trial, MKC-303, was designed to determine whether the addition of Coactinon, a non-nucleoside reverse transcriptase inhibitor, to a three-drug regimen including two nucleoside reverse transcriptase inhibitors and the protease inhibitor nelfinavir, would provide additional benefits to patients with advanced HIV infection. Barry told BioWorld Today the combination of nelfinavir and Coactinon had a "higher-than-expected drug interaction."

In effect, because the two drugs are metabolized by the same liver enzyme, nelfinavir prevented the metabolism of Coactinon. In return, Coactinon doubled the metabolism of nelfinavir, leaving high levels of Coactinon in the bloodstream and very low levels of nelfinavir.

"We have prior studies at lower doses where the interaction isn't as dramatic," Barry said. "But we aren't the only company to find the short-term doses are no predictor of long-term, higher-doses effects."

The company continues to develop the drug and is testing it in Phase II and III studies as a therapy for earlier-stage HIV infection. Barry said it is most likely that Coactinon will find a place in the so-called protease-sparing regimens that keep viral load low without using protease inhibitors.

In any case, the new drug application filing for Coactinon, which was expected later this year, will most likely be delayed. The company is in discussions with the FDA and its marketing partner Abbott Laboratories, of Abbott Park, Ill.

"Abbott's been very helpful to us," Barry said. "We've been going over with them some things we could potentially do."

In June, Triangle announced a marketing deal with Abbott worth up to $335 million. The deal calls for Abbott to partner with Triangle in the U.S. for six antiviral products: two protease inhibitors and four products in development for HIV and hepatitis B. Outside the U.S., Abbott gets exclusive rights to the four Triangle antivirals.

Barry said the company currently has five drugs under active development with additional drugs in the preclinical stage.

"We are very convinced of the portfolio approach," Barry said. "The only way to ensure success is to ensure a good portfolio of products."