Triangle Pharmaceuticals could file an NDA for its anti-HIV product Coactinon (emivirine) by year-end under a $335 mil. co-promotion agreement with Abbott announced June 3.

Coactinon (formerly MKC-442) is one of four Triangle antiviral compounds covered under the agreement. The non-nucleoside reverse transcriptase inhibitor is currently in Phase III development. Abbott expects to file for European approval in mid-2000.

Under the co-promotion agreement, Abbott will purchase 6.57 mil. Triangle shares at $18 per share, and will provide $31.7 mil. in non-contingent research funding and up to $185 mil. in contingent milestone payments.

In return, Abbott will receive co-promotion rights to Coactinon, Coviracil (emtricitabine), and two early stage compounds, DAPD and L-FMAU. Triangle will co-promote Abbott's Norvir (ritonavir), approved in 1996, and the protease inhibitor ABT-378, in Phase III, with an NDA submission expected in 2000.

The agreement could allow the companies to launch one new antiviral product each year for the next four years, Abbott said. The addition of Triangle's antiviral portfolio to Abbott's existing HIV franchise moves Abbott closer to its goal of becoming a leading company in HIV therapies.

The company recently restructured its pharmaceutical division around five "franchises," in neuroscience, anti-infectives, vascular medicine, urology and cardiology, and HIV.

The second compound in the Triangle pipeline, Coviracil (formerly FTC), is part of an ongoing patent dispute between Triangle and BioChem Pharma. The U.S. Patent & Trademark Office has declared an interference between a 1990 BioChem patent covering FTC and its use to treat HIV, and a 1993 Coviracil patent issued to Emory University and licensed to Triangle ("The Pink Sheet" May 10, In Brief).

In May, Triangle settled similar patent litigation with Glaxo Wellcome over the use of Coviracil to treat hepatitis B. Under the settlement, Triangle has access to "development and clinical data and drug substance held by Glaxo relating to Coviracil," the company's first quarter filing notes.

Triangle said it expects the PTO to rule in favor of Emory in its dispute with BioChem Pharma. In a statement following the Abbott/Triangle announcement, BioChem said it "has every intention to continue to vigorously defend and enforce its patent rights."

Patent rights to the third Triangle compound covered under the Abbott agreement are also being disputed with BioChem. DAPD, a nucleoside reverse transcriptase inhibitor in Phase I/II, was included in a 1993 BioChem patent covering a class of nucleosides for the treatment of HIV.

In March, the Opposition Division of the European Patent Office found BioChem Pharma's European patent covering DAPD for treatment of HIV to be valid. Emory is appealing the decision.

Triangle said it expects to come to some form of arrangement with BioChem regarding the DAPD license.

"We expect the costs of the currently pending proceedings to increase significantly during the next several years," the first quarter report states.

"We anticipate that additional litigation and/or proceedings will be necessary or may be initiated to enforce any patents we own or in-license, or to determine the scope, validity and enforceability of other parties' proprietary rights and the priority of an invention."

While the agreement with Abbott does not specifically address assistance with the patent litigation, the funds generated from the stock purchase could potentially be used to offset the costs of the patent disputes. Abbott's purchase of Triangle common stock will generate $118.26 mil. in new funds for Triangle.

The Durham, N.C.-based company will also receive detailing fees and commissions on sales generated by Triangle reps on Abbott products.

The company does not currently have a sales team, but said it will begin building a sales force of 20 to 40 reps to meet the needs of the Abbott agreement.

Abbott has a sales force of 62 focused on the HIV market, with 50 reps and 12 "clinical liaisons" in the field.

Abbott said it expects Triangle to begin promoting the protease inhibitor Norvir by the end of 1999.

Norvir and Glaxo's recently approved Agenerase are the only two protease inhibitors on the market approved for twice-daily dosing ("The Pink Sheet" April 19, p. 3).

Norvir was the fourth leading protease inhibitor on the market until formulation problems discovered in July 1998 forced the company to halt production of its capsule formulation. Capsules comprised 90% of Norvir sales before the withdrawal ("The Pink Sheet" August 3, 1998, p. 21).

Abbott filed an NDA for a soft-gel formulation of Norvir capsules in March. The company believes the new formulation will solve the issues encountered with the original capsule formulation. The soft-gel can accommodate "a new and stable crystalline structure of ritonavir," the company reported. Liquid formulated Norvir has been available since withdrawal of the original capsule.

The second Abbott product to be co-promoted by Triangle, ABT-378, has also been studied as a twice-daily protease inhibitor.

Results of a Phase II trial of the product, presented in February, showed a 93% response rate to ABT-378 in antiretroviral naive patients treated for 20-24 weeks. Data show that 70 of 74 patients achieved HIV RNA levels of less than 400 copies/mL when treated with study drug plus Norvir twice daily.

Abbott and Triangle said the companies expect to execute a manufacturing agreement before finalizing the co-promotion that would allow Abbott to manufacture "certain Triangle products worldwide."

Under the co-promotion agreement, Abbott has also obtained the "right of first discussion" to market future Triangle products. The current agreement only covers the four compounds in human trials.

Abbott/Triangle To File Coactinon In 1999 Under $335 Mil. Co-Promotion

More from Archive

More from Pink Sheet