By Karen Pihl-Carey

The FDA advised Triangle Pharmaceuticals Inc. that the company will have to conduct one, or possibly two, additional Phase III studies of Coactinon (emivirine) in order to prove the drug is superior to HIV products already on the market.

The decision sets Triangle back by about 18 months, if the company decided to move forward with the drug. The company had intended to file a new drug application by the end of this year.

"It's obviously a real challenge for Coactinon because the requirements the FDA has put in are very demanding," said David Barry, Triangle's chairman and CEO. "We will look at the results and some of the interim and/or six-month results from study 401 to determine exactly what it means for Coactinon."

Triangle, of Durham, N.C., will take the first half of 2000 to review results of the ongoing study, MKC-401, which compares the use of Coactinon in conjunction with stavudine and Coviracil (emtricitabine) with a regimen of abacavir, stavudine and Coviracil. Company officials will determine by mid-year whether to continue with more trials.

The company met with the FDA following negative results in October of a Phase III study, called MKC-303. The company unblinded the study and gave patients the option to stop taking Coactinon because of increased side effects, such as nausea and dizziness. Patients also showed no additional clinical benefit from Coactinon added to their highly active anti-retroviral therapy regimen. (See BioWorld Today, Oct. 12, 1999, p. 1.)

"The 303 trial results were critical to the whole package, and absent that, they [the FDA] want additional data," Barry told BioWorld Today. "We had thought an update of the 401 data would be sufficient, and they had indicated that it would not."

The MKC-303 trial was designed to determine whether the addition of Coactinon, a non-nucleoside reverse transcriptase inhibitor, to a three-drug regimen would provide additional benefits to HIV patients.

Triangle intended to accelerate approval of the drug, but the FDA wanted more classical studies that showed more significant data than the MKC-303 trial.

"We know exactly what additional things would have to be done," Barry said, "which is to do at least one and potentially another study comparing Coactinon with other drugs in the preferred regimen for initial patients."

Triangle signed a deal worth up to $335 million with Abbott Laboratories, of Abbott Park, Ill., in June. The two companies partnered on six antiviral products, including Coactinon. (See BioWorld Today, June 4, 1999, p. 1.)

Aside from Coactinon, Triangle has four other drug candidates in the clinic to treat HIV infection and hepatitis B virus. Coviracil is in a Phase II/III trial, and Triangle expects to submit an NDA for it by the end of 2000. DAPD is in Phase I/II ongoing dose-ranging studies, and DMP-450 is in Phase II studies. Finally, L-FMAU is in a Phase I trial for hepatitis B.