Just after announcing a series of changes within its senior management team, Millennium Pharmaceuticals Inc. said it intends early next year to file a new drug application for Velcade, a cancer drug, using Phase II data.
While the company, based in Cambridge, Mass., characterizes the announcements "coincidental," at least one analyst told BioWorld Today to "read between the lines."
"These changes will have an effect," said Yaron Werber, a vice president and biotechnology analyst at SG Cowen Securities. "Three people changing jobs - you have to read between the lines, but you won't get any more from this analyst."
Specifically, Kevin Starr, chief operating and financial officer, will be replaced by Kenneth Bate, formerly a vice president at Biogen Inc. and once a partner at the investment banking firm JSB Partners LP. A company spokesperson said Starr wants to spend more time with his family, but intends to continue working at Millennium in a transition role into 2003.
"I think Kevin has done a very good job and he's been very visible on The Street," Werber said. "He's going to be missed - this is a loss."
In another resignation, John Maraganore, senior vice president, strategic product development, will leave Millennium to join an undisclosed biotechnology company as president and chief executive officer. Werber said Maraganore's resignation is a loss for Millennium as well, because of his work with Velcade.
Finally, Chief Scientific Officer Robert Tepper has been promoted to president, research and development, succeeding Charles Homcy, who has been elected to Millennium's board of directors, replacing Ernest Mario. Homcy also will continue to work with Millennium as senior research and development advisor.
Where does all this leave Velcade? (Also called MLN341, LDP-341 and PS-341).
Publicly, company officials stand by the statement that the two have nothing to do with one another.
Velcade (bortezomib), an injection, is a treatment for relapsed and refractory multiple myeloma. It was granted fast-track status by the FDA.
Millennium intends to disclose results of the 202-patient Phase II trial this weekend at the American Society for Hematology (ASH) meeting Philadelphia.
Werber said the final analysis is expected to be "strong," mirroring preliminary results outlining Velcade's ability to reduce M protein levels, a pathopneumonic surrogate marker for the disease.
At the American Society of Clinical Oncology meeting held last May, Millennium reported preliminary data showing that Velcade stabilized or reduced the myeloma protein in the majority of patients. Also, the company said a majority of patients did not experience disease progression during the 24-week study. (See BioWorld Today, May 21, 2002.)
One concern for Werber, though, is the FDA's apparent movement from accelerated approvals based on Phase II data to approvals based on preliminary Phase III data.
"I don't know why that it is, it could be a number of reasons [including] drug recalls," Werber said, but he acknowledged the Velcade "trial was done well."
Rob Kloppenburg, Millennium's director of communications, agreed with that, and told BioWorld Today that Millennium has been in constant contact with the FDA. "We've locked down good data," he said.
If it reaches the market, Velcade likely will not face much competition because the target group is individuals who are refractory. "These people have nowhere else to turn; they are very desperate," Werber said.
Worldwide, he said the market for this relapsed and refractory indication is probably about 20,000 patients annually, meaning Millennium likely will have to charge $15,000 per annual cost to break even. Best case scenario, at peak, Velcade could bring in $300 million for Millennium, without factoring in any partnering deals, Werber said.
Generally, when a patient is diagnosed with multiple myeloma, he or she has about six months to live, Werber said. Velcade is believed to extend a patient's life to 10 to 12 months.
Millennium said it will complete a 600-patient Phase III trial currently under way, and intends to move ahead with ongoing and new Phase I/II trials in patients with various solid tumors.
Millennium in June initiated the Phase III trial, planned for 60 sites in the U.S., Canada and Europe. It is designed to compare Velcade with high-dose dexamethasone. The primary endpoint is time to disease progression and secondary endpoints are survival, measurements of clinical benefit, quality of life and response rates. (See BioWorld Today, June 13, 2002.)
Millennium hasn't given guidance regarding whether it will conduct other trials for Velcade. Furthermore, it hasn't discussed when the Phase III will be complete, short of stating that patient accrual should be finished by mid-2003.
Millennium gained the rights to MLN341 in 1999 when it merged with LeukoSite Inc., also of Cambridge, Mass., in a $635 million stock deal. (See BioWorld Today, Oct. 18, 1999.)