Bristol Myers-Squibb will pay up to $286 million for development rights to festinavir, a new once-daily nucleoside reverse transcriptase inhibitor that is active against viruses resistant to both tenofovir and abacavir, the company announced on December 20th.
Festinavir is a derivative of d4T (stavudine), but its developers say it is far less toxic than that drug.
Phase 1a trial data presented at the Intersciences Conference on Antimicrobial Agents and Chemotherapy in September 2010 showed that the drug was well tolerated over 10 days of monotherapy in people with previously untreated HIV infection, and test tube studies suggest that the drug is approximately 100-fold less toxic to mitochondrial DNA polymerase gamma than d4T. Mitochondrial toxicity is the cause of the major side-effects associated with d4T, such as peripheral neuropathy and lipoatrophy, that have led to that drug’s declining use.
Festinavir was developed at Yale University in the United States and licensed to Oncolys BioPharma, a Japanese company.
The greatest promise of festinavir lies in its potential activity against HIV with high levels of resistance to current nucleoside analogues. At present no other nucleoside analogue with activity suitable for use by highly treatment-experienced patients is in credible development, and festinavir could be useful for tens of thousands of people with HIV with resistance to three or more drug classes who received extensive prior treatment with nucleoside analogues in the 1990s.
However this cohort of patients is unlikely to have been attractive enough on its own to justify Bristol Myers-Squibb’s investment decision; any company investing $286 million before phase 2 trials have been conducted must see festinavir as a potential big earner, suitable for hundreds of thousands of patients.
Bristol-Myers Squibb will now take forward the development of the drug, seeking to establish the optimal dose. Phase 1a results indicated little difference in the degree of virlogical suppression between daily doses of 300mg or 600mg, and as 3TC (lamivudine) goes off patent, it could be tempting for Bristol-Myers Squibb to pursue a development path that co-formulates festinavir with its own generic version of 3TC, in a branded nucleoside analogue combination that competes with Gilead’s Truvada (tenofovir and FTC) and Glaxo SmithKline’s Kivexa (abacavair and 3TC).
Co-formulation could also allow the company the company to come up with fixed dose combinations that match the pair with efavirenz or with atazanavir, ensuring that Bristol-Myers Squibb remains a central player in the HIV drug market for years to come.
As patents on some of the major elements of HIV therapy begin to expire between now and 2018, the search for new agents and new drug classes will be accompanied by an intensification of approaches to re-formulating drugs in ways that extend the patent life of big earners while delivering greater convenience in dosing for patients.