Two compounds to treat HIV are headed in decidedly divergent directions, according to news released by Triangle Pharmaceuticals Inc. Friday.
The company said it plans to submit a new drug application this fall for Coviracil while at the same time terminating further development of Coactinon.
For Coviracil, the news evidences a measure of success for a drug that has seen some ups and downs with regard to its development. If the company submits the NDA, expected in the third quarter, it would become Triangle’s first product for which an NDA is submitted.
“I never speculate about what the FDA will do,” Chairman and CEO David Barry said in a conference call Friday. “Certainly, we’ll be submitting then; certainly, I would hope for a filing, but I can’t guarantee anything. But certainly the full submission . . . will be in the third quarter.”
The company originally planned to submit the NDA this quarter for Coviracil, a nucleoside reverse transcriptase inhibitor licensed from Emory University in Atlanta. The NDA was to be based on a trial called FTC-302 and another Phase III study, FTC-303. But the delay became apparent when the FDA indicated that data from the FTC-302 Phase III trial were insufficient. As a result, the company reduced its work force by 35 percent. (See BioWorld Today, Aug. 8, 2001.)
A year before, the South African Medicine Council recommended the Durham, N.C., company stop the FTC-302 trial because of concerns with liver toxicity. Instead, Triangle continued to treat existing patients without adding new ones. (See BioWorld Today, April 7, 2000.)
“The study from Africa will be included as part of the supportive data, but not as a pivotal study, as I understand it,” Barry said.
“[The FDA] continued to adhere to its position that obviously they’d look at the data from a supportive standpoint,” President and COO Chris Rallis told BioWorld Today. “But they did not consider that study to be pivotal, so that’s what led to the delayed submission, or change in plan, for the Coviracil submission.”
Before that news, Triangle began a third trial, FTC-301, a 100-site Phase III study that enrolled more than 500 patients in the U.S., Europe and Latin America.
“We completed enrollment in that in November,” Rallis said. “One of the challenges in today’s HIV drug development area is when your patient population is treatment na ve, it does take quite some time to enroll that number of patients.”
Triangle stands to receive potential reimbursement milestones from Abbott Park, Ill.-based Abbott Laboratories of up to $85 million after approval and launch of Coviracil for HIV in the U.S. and Europe.
“We’re optimistic about the commercial potential of Coviracil,” Rallis said.
Currently, a pivotal trial is ongoing in the treatment of hepatitis B infection with the candidate, with a second study on the way.
“We are in a Phase III study with hepatitis,” Barry said. “We hope to have more of an update in our quarterly earnings report, which should come out in the first half of February.”
Regarding Coactinon, the company recently completed a planned interim analysis of 24-week data from study MKC-401. Although interim analysis results did not trigger predefined criteria for stopping the study, data indicated that Coactinon was not performing as well as its comparator drug, abacavir, across the full study population.
The expanded trial began in 2000, aimed at using a lower dose of Coactinon (500 mg twice daily vs. 750 mg twice daily).
“As do all drug candidates, it had its set of challenges, including some metabolism issues,” Rallis said. “As this 24-week interim analysis indicated, the equivalence to abacavir was not being demonstrated and the trend of the data was not going in the right direction.”
Therefore, Triangle elected to discontinue development of Coactinon and allocate the company’s personnel and other resources to more promising drug candidates.
“It’s not a point you want to reach with regard to the development of any drug product,” Rallis said, “but fortunately we have Coviracil, amdoxovir and clevudine, which are all in the clinic and about which we’re very enthusiastic.”
The company plans to begin several Phase II trials in HIV for amdoxovir (DAPD) this year. Clevudine (L-FMAU) is in an ongoing Phase I/II study for the treatment of hepatitis B infection, and a Phase II program is planned to begin this year.
Triangle stands to receive additional potential milestones of up to $35 million upon obtaining regulatory approvals of amdoxovir and clevudine in the U.S.
As part of a 1999 agreement, Triangle and Abbott have joint rights to commercialize Coviracil, amdoxovir and clevudine in the U.S. Outside the U.S., Abbott would have exclusive commercialization rights for these drug candidates.
Triangle’s stock (NASDAQ:VIRS) fell 27 cents Friday to close at $3.73.