Truvada combo a no go?

22 August 2005 00:01  [Source: ICB Americas]

Despite recent disappointments, Gilead Sciences Inc. intends to push forward with the development of a new HIV combination pill joining Gilead’s Truvada (emtricitabine and tenofovir disoproxil fumarate) with Bristol-Myers Squibb Co.’s Sustiva (efavirenz). The companies plan to use a bi-layer technology to develop up to three new formulations of the proposed combination.

Gilead suffered a clinical setback earlier this month when its second attempt at a Truvada/Sustiva fixed-dose formulation failed to demonstrate bioequivalence in HIV treatment compared to the individual products used separately. Prior to that, the company’s first attempt at a formulation yielded similar results. In April, Gilead released preliminary bioequivalency study results on the first formulated combination dose, which demonstrated lower levels of efavirenz in the blood. This was compared to the recommended 600 mg dose of Sustiva alone.

As a result of both findings, Gilead has pushed back its regulatory filing timetable. Gilead and partner Bristol-Myers Squibb now expect to submit a new drug application (NDA) to the Food and Drug Administration in the first half of 2006. The companies had initially targeted filing an NDA by the end of this year.

The bi-layer technology that Gilead is using will involve the coformulation of Truvada and Sustiva as separately formulated layers combined in one tablet.

Gilead will conduct bioequivalence studies in human patients and stability studies of the new formulations in the next several months. The company expects to evaluate up to three new bi-layer-based formulations.

Analysts are bullish that Gilead can stand on the success of Truvada, itself a fixed dose combination (FDC) tablet of Viread (tenofovir disoproxil fumarate) and Emtriva (emtricitabine).

Since its launch last year, Truvada has had a rapid uptake and is expected to challenge the dominance of Combivir as the favored nucleoside reverse transcriptase inhibitor (NRTI), according to London, UK-based Datamonitor PLC.

Combivir, a FDC of Retrovir (zidovudine) and Epivir (lamivudine) by GlaxoSmithKline (GSK), is still the class leader among NRTIs. Commonly used in first-line therapy, Combivir has experienced steady growth since its launch in 1997. It achieved $914 million in sales in 2004, a 6.6 percent increase over the previous year, according to Datamonitor.

However, over the next five to 10 years, Combivir’s class and market dominance will be challenged by products like Truvada and GSK’s Epzicom (lamivudine/abacavir), two new FDCs launched in 2004. “Comparative trials of Combivir, Truvada and Epzicom have demonstrated superior efficacy of Truvada versus Combivir and equivalence between the two GSK products,” says Laura Harris, Datamonitor’s senior HIV analyst.

Truvada is expected to be the dominant FDC by 2015, with sales reaching $874 million that year. Epzicom is forecast to reach peak sales of $490 million in 2009.

NRTIs are the backbone drugs in HIV treatment, and they continue to dominate the market, says Datamonitor. The NRTI class captured 55 percent of the market in 2004, translating into $3.7 billion in sales, making it the predominate and fastest growing class of antiretrovirals.

“This strong growth can be primarily attributed to two relatively new drugs—GSK’s Trizivir (lamivudine/zidovudine/abacavir) and Gilead’s Viread, which generated $574 million and $739 million of sales in 2004, respectively,” says Harris.

By: Feliza Mirasol
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