West Coast Editor

The early stop thanks to efficacy of Millennium Pharmaceuticals Inc.'s Phase III trial with Velcade in new multiple myeloma patients left a key question unanswered, as the firm rolls toward a supplemental new drug application in the front-line setting "as fast we can, but by the first quarter of 2008," said Deborah Dunsire, president and CEO.

Results showed that Velcade, when combined with the other two drugs (Velcade-MP), yielded a "highly statistically significant improvement" in all efficacy measures, including time to disease progression, complete remission rate, progression-free survival and overall survival, compared to melphalan and prednisone given alone, Millennium said.

The outcome "positions Velcade as a new standard of care," Dunsire told investors during a conference call. Wall Street apparently was not surprised that Velcade worked in previously untreated MM, and Millennium's shares (NASDAQ:MLNM) rose a modest 88 cents Tuesday to close at $10.65.

Detailed results of the study are due at the American Society of Hematology meeting in December, when the world learns how Velcade's results stack up with the performance of Summit, N.J.-based Celgene Corp.'s Revlimid (lenalidomide, a derivative of Thalomid, the company's brand name for thalidomide). Celgene's stock (NASDAQ:CELG) closed Tuesday at $69.29, up $1.54.

Orally administered Revlimid was approved in June 2006 for use against MM in combination with dexamethasone in patients given at least one prior therapy, and the intravenous proteasome inhibitor Velcade (bortezomib) won clearance in 2005 for the same patient group, having been approved for relapsed/refractory disease earlier. (See BioWorld Today, May 15, 2003.)

Cambridge, Mass.-based Millennium's trial, called VISTA (Velcade as Initial Standard Therapy in MM: Assessment with Melphalan and Prednisone), started in January 2005 with Johnson & Johnson Pharmaceutical Research & Development, a unit of New Brunswick, N.J.-based Johnson & Johnson, and enrolled 682 elderly patients.

Based on word from an independent data monitoring committee, the control arm of the trial was halted early to let patients still being treated with the non-Velcade regimen to have Millennium's drug added to their therapy.

Company watchers await details at ASH on Velcade's response rate and one-year overall survival, where beating Revlimid could be tough. The Celgene compound showed 96 percent survival at one year when combined with dexamethasone in a 450-patient Phase III trial, and 100 percent in a much smaller, Phase II trial when given with the pair of drugs used in Millennium's study. The oral dosing route for Celgene's drug is an advantage, too.

VISTA's data could fall in line with those from Millennium's impressive Phase II study with Velcade-MP, which gained a 43 percent complete response rate in front-line MM, with a 38-month survival by 85 percent of patients. Approval for use in new patients "should lead to some additional penetration," wrote analyst Bret Holley with CIBC World Markets in a research report Tuesday.

"However, given our expectation that Thalomid, and increasingly Revlimid, will have a primary role in front-line treatment, we do not expect market share gains for Velcade to be substantial," he wrote. Down the road, combining Velcade with Thalomid or Revlimid could hold promise, and trials are testing those combos.

Dunsire spoke to the same subject during the conference call.

"What we're seeing here is the power of the combination of therapy, which you've seen across all different cancers - breast cancer, lymphoma - where multidrug combinations are coming together to really change the outcomes for patients," she said.

Christophe Bianchi, vice president of commercial operations for Millennium, said Velcade is "already the most efficacious single agent product for the relapsed setting for MM," and results with a Velcade regimen in the front line likely will "compare very well" to existing approaches.

Questioned by an analyst, he said U.S. physicians probably will use Velcade-MP because of its efficacy, as seen in the "spectacular" results from the Phase II trial, though some will swap the MP backbone for dexamethasone. "MP, in and of itself, is the standard of care on a global basis," Bianchi pointed out, though the combination is not much used in the U.S.

Millennium sells Velcade here, and Janssen-Cilag AG (a unit of J&J) is responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical KK markets the drug in Japan.