New formulations, acquisitions and company announcements

1 December 2011. Related: Antiretrovirals.

Simon Collins, HIV i-Base

The last two months have been a lively time for pharmaceutical industry announcements concerning Fixed Dose Combinations (FDCs) and new compounds in the HIV and hepatitis pipelines.

Integrase FDC Quad submitted to the FDA

At the end of October, Gilead submitted a new drug application (NDA) to the US regulatory agency (FDA) for its four-drug formulation of elvitegravir, cobicistat, tenofovir and FTC (Quad). This is based on 48-week data from two Phase 3 studies.

Three weeks later Quad was also filed with the European Medicines Agency (EMA).

If these applications are given a fast track review a decision will be made by both agencies within six months.

Reference: Gilead press release: Gilead submits new drug application to U.S. FDA for once-daily, single-tablet ‘Quad’ HIV regimen (27 October 2011).

Planned co-formulations of cobicistat with atazanavir, darunavir and darunavir/FTC/GS7340

On 26 October, Bristol-Myers Squibb (BMS) announced that it has entered an agreement to develop and market an FDC of its protease inhibitor atazanavir (Reyataz) with a pharmacokinetic booster cobicistat, currently in development with Gilead. [1]

Phase 2 and 3 studies of atazanavir using cobicistat boosting are ongoing in treatment-naive patients.

Cobicistat has a similar inhibitory impact on cytochrome P450 3A (CYP3A) and similar side effect profile to ritonavir.

Earlier this year a similar agreement was reached between Gilead and Tibotec to produce an FDC of darunavir with cobicistat. [2]

The press release also referred a further collaborate to produce an FDC of darunavir plus FTC together with cobicistat plus the new tenofovir prodrug (GS7340).

Reference:

1. Press release: Bristol-Myers Squibb and Gilead Sciences announce licensing agreement for development and commercialisation of new Fixed Dose Combination pill for People Living with HIV. (26 October 2011).
2. Press release: Gilead Sciences announces agreement with Tibotec Pharmaceuticals to develop and commercialise a new fixed-dose combination of cobicistat and darunavir (Prezista). (28 June 2011).

Gilead license integrase inhibitor compounds from Boehringer Ingelheim

Gilead acquired a license for exclusive worldwide rights for the research, development and commercialisation of its novel non-catalytic site integrase inhibitors (NCINIs) for HIV. This includes the lead compound BI 224436, which has been evaluated in a Phase 1a dose-escalation study to assess bioavailability and pharmacokinetics in healthy volunteers.

NCINIs inhibit HIV integrase by binding to a novel site, distinct from the catalytic site used by the current class of integrase inhibitors, and therefore may possess a differentiated resistance profile from raltegravir or elvitegravir.

Reference:
Press statement: Gilead and Boehringer Ingelheim sign license agreement for novel HIV non-catalytic integrase inhibitors. (05 October 2011).

Gilead spends $11 billion to buy Pharmasset

Finally, on 21 November 2011, Gilead announced that it would acquire Pharmasset for the not insignificant cost of $11 billion from “cash on hand, bank debt and senior unsecured notes”.

Pharmasset currently has three clinical-stage product candidates for the treatment of chronic hepatitis C virus (HCV) advancing in trials in various populations.

• The lead product compound, PSI-7977, an unpartnered uracil nucleotide analogue, has recently been advanced into two Phase 3 studies in genotype 2 and 3 patients. Both studies use 12 weeks of treatment with PSI-7977 in combination with ribavirin. Comparitor arms include pegylated : ?interferon/ribavirin in treatment-na? patients, and placebo in interferon- intolerant/ineligible patients. A third Phase 3 study in genotype 1 patients will be initiated in the second half of 2012.
• PSI-938, an unpartnered guanosine nucleotide analogue, is being tested in a Phase 2b interferon-free trial as monotherapy and in combination with PSI-7977 in subjects with HCV of all viral genotypes.
• Mericitabine (RG7128), a cytidine nucleoside analogue, is partnered with Roche and is being evaluated in three Phase 2b trials. Roche is responsible for all aspects of the development of mericitabine.

Reference:
Press statement: Gilead Sciences to acquire Parmasset Inc for $11 billion. (21 November 2011).

Abbott to separate treatment from medicinal products in company split

Abbott, the research-based company responsible for developing lopinavir/ritonavir (Kaletra) and ritonavir (Norvir) which has a annual revenue close to $18 billion dollars announced that it plans to divide into two separate companies: one focused on research and treatment and the other on diversified medical products.

The press statement listed immunology, Multiple Sclerosis, chronic kidney disease, Hepatitis C, women’s health and oncology, but not HIV, as future research priorities.

Reference:
Press statement: Abbott to Separate into Two Leading Companies in Diversified Medical Products and Research-Based Pharmaceuticals. (19 October 2011).