West Coast Editor

Millennium Pharmaceuticals Inc. provided a conference call update in which the firm again predicted profitability in 2006, and forecast annual sales of its multiple myeloma drug Velcade in the range of $225 million to $250 million - a revenue goal that raised the eyebrows of some analysts.

But the company's president and CEO, Deborah Dunsire, said she intends to hit those numbers, and referred to the proteasome inhibitor as "a terrific product that hasn't yet made the most out of all the data" supporting it, even as more data flow in.

The company's stock (NASDAQ:MLNM) closed Friday at $10.22, up 17 cents.

Dunsire pointed to results offered at the recent American Society of Hematology in Atlanta testing Velcade alone or in combination with other commonly used agents in previously untreated multiple myeloma, resulting in overall response rates as high as 92 percent, with complete response rates as high as 30 percent.

Cambridge, Mass.-based Millennium also reported that Velcade (bortezomib), used alone or in combination, in a range of multiple myeloma populations showed overall response rates of up to 78 percent in relapsed and refractory patients, a population in which the landmark Phase III APEX trail demonstrated a median 30-month survival benefit for Velcade as a single agent.

"We've known about [the potential as a combination therapy] all through Velcade's life, but we really saw that at ASH," Dunsire told BioWorld Today. What's more, it can be used across a broad range of patients, even those with renal failure, she said.

The compound won approval for third-line treatment of multiple myeloma in May 2003 on data from a 202-patient Phase II study known as the SUMMIT trial, showing median survival time in relapsed and refractory patients to 16.4 months. They usually die six to nine months after they are diagnosed.

Cleared in the second-line setting in March, Velcade sold $192 million last year, a jump of 34 percent over the previous year, Millennium reported, which means fourth-quarter sales hit $52 million, in line with Wall Street estimates. Millennium has vowed to grow Velcade sales another 17 percent to 30 percent this year.

"We have three front-line trials running," Dunsire said, and a label expanded to include those patients could mean even better things for Velcade. "Any of those trials could deliver an approval."

Meanwhile, Velcade finds itself under pressure from Warren, N.J.-based Celgene Corp.'s Revlimid (lenalidomide, a derivative of Thalomid, the company's brand name for thalidomide), which gained FDA clearance in late December for myelodysplastic syndromes. A supplemental NDA filing is expected shortly, seeking the go-ahead to officially target multiple myeloma. (See BioWorld Today, Dec. 29, 2005.)

Dunsire was quick to point out that Velcade is "the only single agent ever shown to provide a survival advantage" in multiple myeloma, which she called "really a key driver. When physicians know that, they think about Velcade differently."

Educating physicians with an expanded sales force - while making the most of the data now available and gathering more - will be Millennium's main tasks.

For example, the company knows that "not all patients are getting eight cycles [of therapy]," Dunsire said. "If you want to buy in to the survival advantage, it comes with eight cycles of therapy."

Among the skeptics is analyst Jim Reddoch, with Friedman, Billings, Ramsey & Co. in Arlington, Va., who called the midpoint of Millennium's Velcade sales guidance "tough to achieve," and noted in a research report that the firm expects modest net income of up to $5 million this year, "basically in line with previous guidance. Breakeven is made achievable more by layoffs than top-line growth."

In the works at Millennium is a Phase III trial with Velcade comparing the compound with and without Rituxan (rituximab), from South San Francisco-based Genentech Inc., against relapsed/refractory, indolent non-Hodgkin's lymphoma, as well as a study in lung cancer.

Both of those ventures are "high risk," in Reddoch's view, and he predicted no other Phase III studies by Millennium until at least 2007. Another candidate, MLN2704 for prostate cancer, seems unlikely to reach Phase III, he added, given the company's "tepid comments" during the conference call.

Dunsire said that when Millennium "put [MLN2704] in Phase I proof of concept, we were looking for some activity, which we did see, but we also saw some neuropathy develop. We've opened a final cohort and that's what we're moving through now." A decision on the next step is expected in the first half of this year, she said.

Another compound moving along, though, is MLN1202, the CCR2 blocker that in August began a 110-patient Phase II trial in patients at risk for atherosclerotic cardiovascular disease. Two other proof-of-concept trials are ongoing, as well, including one in rheumatoid arthritis and one in multiple sclerosis. Another in sclerodoma will begin soon.

"We should be able to look at RA and [the atherosclerosis data] during the second half of 2006," said Dunsire, who took over during the summer as the replacement for Mark Levin, who also is Millennium's co-founder. She left her post as head of oncology operations in North America for Novartis Pharmaceuticals Corp., of East Hanover, N.J., the U.S. affiliate of Novartis Pharma AG in Basel, Switzerland. Dunsire worked for Novartis for almost 20 years. (See BioWorld Today, July 6, 2005.)

Reddoch, who maintains an "underperform" rating, characterized Millennium as a "slowing-growth company with a high valuation and an early stage pipeline."

Analyst Phil Nadeau at SG Cowen in New York remained "neutral" on Millennium's shares, citing in a research report "many pipeline milestones in 2006, although none seem sufficient to spark investor interest."

Christopher Raymond, with Robert Baird & Co. in Chicago, also stayed "neutral," and said in a research note that his firm "continue[s] to await signs of increased Velcade traction before recommending the name."

Analysts at Atlanta-based Suntrust Robinson Humphrey downgraded Millennium from "buy" to "neutral" in December. Last fall, Lehman Brothers in New York upgraded the firm from "underweight" to "equal weight."

Reddoch said Velcade is "showing a plateau," but Dunsire disagreed.

"Growth in 2005 vs. 2004 was very strong," she said. Along with the Rituxan combo trial, the company will submit in the second half of this year a supplemental BLA filing to explore Velcade against mantle cell lymphoma. But even without the new indications, "a number of myeloma patients out there in the relapsed settings are getting some old therapies, and there's room for Velcade to penetrate further. We have a really good base for a company that's just 13 years old."