Pipeline - Pharmaceutical Executive


Rays of Light

Pharmaceutical Executive


Nezam Afdhal, Beth Isræl Deaconess Medical Center
Hepatitis C has long presented a golden opportunity for innovative drug development. The gold-standard therapy, a combo of pegylated interferon and ribavirin (IFN/RVN), rakes in $3 billion a year and counting, despite major downsides, including 48 weekly injections complete with a side effect dubbed "the flu from hell," a 50 percent failure rate, and a price tag of $25,000. Enter Novartis, the crafty Swiss pharma giant: To take the pulse of the HCV pipeline, just check out which compounds it's betting licensing bucks on.

The treatment picture for hep C is about to switch from black and white to color, with more options that are kinder to patients and meaner to the virus. Tomorrow's standard of care will consist of triple-drug combos that attack fast-mutating HCV from different angles, as in the model for HIV.

"As we enter the age of STAT-C—Specifically Targeted Antiviral Therapy for HCV—the future of treatment looks very promising," says Nezam Afdhal, MD, chief of hepatology and director of the Liver Center at Beth Israel Deaconess Medical Center. "These small molecules should enable us to make people negative more quickly, with fewer side effects, and increase the cure rate."

Vertex's telaprevir (VX-950), a cleanly designed protease inhibitor, is the most ambitious advance—and the one Novartis failed to nab (J&J will co-promote). The small molecule blocks an enzyme critical to HCV replication, and early data show that it clears the virus four times faster than IFN/RVN, with a 70 percent success rate and few nasty side effects. Although its current three-times-a-day oral formulation may present adherence problems, pills beat interferon injection hands down. Vertex is currently conducting two big Phase II studies to PROVE (the trial's hopeful name) that adding VX-950 to IFN/RVN cuts the virus faster and better.

Another straight-shooting antiviral, Idenix's Valopicitabine (NM-283), knocks out HCV's RNA polymerase. Nowhere near as fast-acting as the Vertex compound, Valopicitabine does have the advantage of once-daily dosing—although Phase II data found iffy gastro complications. Next up: Phase III trials pitting NM283/INF/RBV against NM283/INF as first-line and back-up.

Human Genome Sciences' HCV contestant is Albuferon, a high-tech entry in the race for the pegylated interferon market. By fusing the immune modulator with human albumin, a highly concentrated protein found in blood plasma, the savvy biotech was able to design a slow-release version. According to recent Phase II data, one shot of Albuferon every two weeks works at least as well as a once-a-week shot of pegylated interferon. Phase III studies are enrolling with double-dose monthly injections—and hoping to ACHIEVE (another winning trial name) good safety data.

Cut to Novartis and its recent hep C spending spree. The company has bought marketing dibs on four biotech-built compounds: Albuferon, Valopicitabine, and two Phase I small molecules with unique mechanisms of action. Together with its generic ribavirin Sandoz deal, this portfolio may have Novartis playing hep C bartender, mixing and matching state-of-the-art drug cocktails for years to come. –WA

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