Achillion’s lead product candidate, elvucitabine, is an L-cytosine nucleoside analog reverse transcriptase inhibitor (NRTI) that has demonstrated potent antiviral activity against HIV, including strains resistant to other NRTIs. L-cytosine NRTIs represent the most frequently prescribed class of NRTIs based upon sales, accounting for approximately 34% of the worldwide NRTI market in 2004. L-cytosine NRTIs are frequently prescribed given their established potency, favorable short-and long-term safety profile and fewer and less severe adverse side effects.
Achillion believes elvucitabine addresses the limitations of currently available NRTIs in the following ways:
Long Half-Life. Elvucitabine’s plasma half-life has been demonstrated in clinical trials to be approximately 100 hours, or up to 20 times greater than that of Epivir (3TC) and up to ten times greater than that of Emtriva (FTC). In addition, elvucitabine’s intracellular half-life has been demonstrated in a clinical trial to be over 100 hours, or more than five times greater than that of Epivir (3TC) and Emtriva (FTC). This long half-life may mitigate the negative effects of less than perfect patient compliance, providing a more durable NRTI for use in HAART regimens.
Superior Potency Against Common Resistance Mutations. The laboratory antiviral profile of elvucitabine demonstrates superior potency against many of the most common resistance mutations associated with NRTIs typically used in combination with Epivir (3TC) and Emtriva (FTC), including those associated with Viread (tenofovir), Retrovir (AZT) and Zerit (d4T). In addition, although elvucitabine’s resistance profile is similar to Epivir (3TC) and Emtriva (FTC), elvucitabine retains greater antiviral activity in laboratory tests against HIV with resistance to Epivir (3TC) and Emtriva (FTC). This enhanced antiviral activity could provide an increased barrier to the emergence of drug resistance in patients and improve antiviral suppression in patients with emerging resistance to commonly used NRTIs.
Patient Compliance. A well tolerated L-cytosine NRTI with convenient, flexible oral dosing could significantly enhance patient compliance and would make elvucitabine an attractive component of HAART regimens. With a projected daily dose of elvucitabine of 10 mg in a tablet formulation, compared to 200 mg for Emtriva (FTC) and 300 mg for Epivir (3TC), elvucitabine could also be an attractive candidate as part of a fixed-dose combination product for use in HAART regimens.
Market data indicate that the vast majority of patients (84%) are currently taking a cytosine nucleoside as part of their therapeutic regimen, including more than 90% of first-line patients and approximately 70% of treatment-experienced patients. Given the prevalence of the cytosine class, and elvucitabines superior potency, good tolerability, its pharmacokinetic barrier to the emergence of resistance, and its overall range of activity against resistant mutations, we expect elvucitabine to be positioned to take market share in both segments of the overall HIV market.
In segmenting the market opportunity, Achillion divides the HIV market broadly into two categories: first-line, or treatment-naïve patients who are presenting for treatment for the first time, and treatment-experienced patients who may still be on their first treatment regimen, but who, more likely, have failed their first, second or even third regimen. While Achillion does not expect elvucitabine to penetrate much into the treatment-naïve group, as a single agent, the Company believes elvucitabine could enjoy meaningful market penetration, if ultimately approved, in a fixed combination, or a single agent, given the favorable characteristics described above.
