Washington Editor

Millennium Pharmaceuticals Inc. filed a new drug application for Velcade, a proteasome inhibitor shown to extend median survival time in relapsed and refractory multiple myeloma patients to 16.4 months.

Multiple myeloma patients commonly die within six to nine months of diagnosis and have few treatment options. However, data from Millennium's new drug application (NDA), which is based primarily on a Phase II trial referred to as SUMMIT, showed that a majority of the 202 participants experienced a reduction or stabilization in their disease severity, with some patients experiencing complete remission. Furthermore, the multicenter trial demonstrated a 35 percent response rate in patients who were progressing on their last therapy. (See BioWorld Today, Dec. 10, 2002.)

Millennium, of Cambridge, Mass., released those data in December at the 44th annual meeting of the American Society of Hematology in Philadelphia, several days after saying it would file the NDA in early 2003. (See BioWorld Today, Dec. 6, 2002.)

"The submission of this NDA represents a significant milestone for Millennium and an important step toward fulfilling our mission of making novel treatment options available to patients with significant unmet medical needs," Robert Tepper, Millennium's president, research and development, said in a prepared statement. "Since the initial Velcade patient dosing just over four years ago, we have been committed to the thorough and expeditious clinical development of Velcade and are proud that this strategy has resulted in an accelerated filing."

Velcade (bortezomib), a drug taken by injection, has been awarded both fast-track and orphan drug status. The company filed the NDA under accelerated approval provisions that, if granted, would require the agency to take action in six months. Millennium said Velcade is the first and only proteasome inhibitor currently being evaluated in clinical trials for the treatment of cancer.

Indeed, Mark Schoenebaum, a biotechnology analyst with CIBC World Markets Corp. in New York, told BioWorld Today the FDA likely will call for an advisory panel to hear Velcade's case before approving it, possibly six months down the road.

Research notes released by Bill Tanner, managing director with Leerink Swann & Co. in Boston, said the early 2003 filing indicates that Velcade could enter the market in the late 2003 time frame. Tanner estimates that U.S. sales could reach $100 million in refractory multiple myeloma.

Schoenebaum said CIBC estimates the multiple myeloma world market at $200 million to $400 million.

He added, "We think the initial product label will be the salvage [patients who have failed several lines of therapy] multiple myeloma market. However, it is our belief that many physicians will quickly be experimenting with use earlier in the disease."

Based on conversations with Millennium management, Leerink Swann expects Millennium to partner Velcade for geographic and other market opportunities.

Meanwhile, Millennium has an ongoing international, multicenter Phase III trial of Velcade, named APEX, in multiple myeloma patients. APEX compares Velcade with high-dose dexamethasone in patients who have received one to three previous treatments and are relapsed or refractory.

Steve Sylven, spokesman for the company, said Millennium expects to finish accruing the 600-patient Phase III trial by the end of 2003. While it likely would take six to nine months to analyze the data, Sylven wouldn't comment on a timeline as to when the company believes data could be ready for the FDA.

Sylven said Millennium expects to file in Europe during the first half of 2003.

In other news released late last week, Millennium said it initiated a Phase II trial of Velcade in patients with Stage IIIb or Stage IV non-small-cell lung cancer, and in late December the company started a Phase II trial in 175 colorectal cancer patients. Velcade also is the subject of Phase I and II trials in patients with hematologic and solid tumors.

Millennium acquired Velcade, formerly known as MLN341, LDP-341 and PS-341, in 1999 when it merged with LeukoSite Inc., also of Cambridge, Mass., in a $635 million stock deal. (See BioWorld Today, Oct. 18, 1999.)

Millennium's stock (NASDAQ:MLNM) closed Wednesday at $8.28, up 10 cents.