Schering-Plough, Incyte Report Positive Mid-Stage Data For CCR5 Antagonists

Both Schering’s vicriviroc and Incyte’s INCB9471 CCR5 antagonist candidates to treat HIV beat placebo in Phase II trials.

Two firms developing CCR5 receptor antagonists for the treatment of HIV reported positive Phase II results at an AIDS research meeting in Australia July 24.

Researchers reported results of a randomized, double-blind Phase II study of Schering-Plough's once-daily HIV treatment candidate vicriviroc in 118 treatment-experienced HIV patients with R5-type virus who were already on treatment regimens containing a ritonavir-boosted protease inhibitor.

Change from baseline in viral load at day 14 was the primary endpoint. Median change in HIV-1 RNA for 10 mg and 15 mg vicriviroc treatment groups was -1.57 log and -1.15 log, respectively, compared with the placebo group at +0.06 and -0.29 (p<0.01).

In addition, "A much higher percentage of patients on vicriviroc [57 percent of those dosed at 10 mg] were able to become undetectable and remain undetectable through 48 weeks. In the placebo arm it was only ... 14 percent," Schering told "The Pink Sheet" DAILY.

"The key finding here is the long-term suppression of the virus over 48 weeks, so a durable response, and more patients in the vicriviroc arms were able to achieve undetectable levels of the virus versus placebo, and fewer patients in the vicriviroc arms had virological failure versus placebo," the firm emphasized.

Incyte's 14-day Phase IIa placebo-controlled trial of its CCR5 candidate, INCB9471, involved 23 HIV-infected subjects - both treatment-naive and treatment-experienced - harboring R5-tropic virus who had not received antiretroviral treatment for a minimum of three months.

Incyte's INCB9471 is designed to be administered without ritonavir, a protease inhibitor associated with cardiovascular risk, according to the firm.

Patients treated with 200 mg of '9471 once-daily achieved a mean viral load change of -1.72 log at day 14, with a nadir for the mean viral load of -1.81 log occurring at day 16. At day 28, mean change in viral load was -0.81 log.

There was no significant difference in grade 3 or 4 adverse events across the vicriviroc and placebo groups, however eight vicriviroc-treated patients and two placebo-treated patients developed malignancies, according to Schering.

In the '9471 study, the drug was well tolerated, with no clinically significant chemistry, hematology or ECG changes in treated patients compared with placebo patients, Incyte said.

The findings were presented July 24 at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Sydney, Australia.

CCR5 antagonists prevent the HIV virus from entering uninfected cells by blocking its predominant entry route, the CCR5 co-receptor.

Pfizer's maraviroc, another CCR5 candidate, to treat HIV in patients whose virus has become resistant, recently received an "approvable" letter from FDA (¹ (Also see "Pfizer’s Maraviroc Deemed “Approvable” By FDA" - Pink Sheet, 21 Jun, 2007.)).

Though Pfizer did not identify the issues raised by the agency, an FDA advisory committee earlier this year voiced concerns about the possibility of malignancies, infections and cardiovascular complications (² (Also see "Pfizer’s Maraviroc Unanimously Recommended For Accelerated Approval" - Pink Sheet, 25 Apr, 2007.)). Even so, the panel unanimously recommended the candidate for accelerated approval.

Schering has an ongoing randomized, double-blind, placebo-controlled Phase II trial of vicriviroc (VICTOR E-1) in which treatment-experienced patients are dosed once daily with either 20 mg or 30 mg vicriviroc plus an antiretroviral regimen. Based on those results, the firm said it will select a dose to move forward with Phase III trials.

In June, Schering began enrolling patients in a 375-patient Phase III trial studying vicriviroc in combination with an optimized antiretroviral regimen. That study is expected to be completed in November 2009.

Wilmington, Del.-based Incyte is evaluating 100 mg and 300 mg once-daily doses of '9471 to support two six-month Phase IIb studies it expects to complete by first quarter 2008 (³ (Also see "Incyte’s CCR5 Antagonist Has “Meaningful Advantages” Over Pfizer’s Maraviroc, Firm Says" - Pink Sheet, 3 May, 2007.)).

-Pamela Taulbee ([email protected])