Millennium Velcade Has 50%-60% Of Third-Line Multiple Myeloma Market

Millennium's Velcade captured 50% to 60% of the third-line multiple myeloma market in the second quarter, the firm reported July 22.

In the previous quarter, "we had estimated penetration in the third-line and beyond setting of 30% to 40%. We had estimated second-line use around 10% and front-line was minimal," VP-Sales & Marketing Bob Terifay told investors on a second quarter earnings call.

The firm also saw increases in second-line and front-line use of the proteasome inhibitor in the second quarter, with 10% to 20% market share in second-line use and under 10% in front-line.

While Velcade (bortezomib) is indicated for "treatment of multiple myeloma patients who have received at least two prior therapies," Millennium anticipates a significant increase in use across all stages of therapy within the next year.

"Our [market] information shows that over the next year, third- and fourth-line usage will continue to increase, second-line usage will grow dramatically, and front-line adoption will become significant," Exec VP & Head of Commercial Operations Kenneth Bate said.

Velcade net sales for the second quarter were $35 mil., up 18% from the first quarter.

Millennium launched Velcade in the U.S. on May 20, 2003. In its first 14 months on the market, sales totaled $125 mil. Millennium confirmed its Velcade sales projection of $140 mil. to $160 mil. for 2004.

One of the firm's key growth strategies for Velcade is a planned filing for full approval in second-line use. Millennium expects to submit an sBLA in the second half of 2004 based on the Phase III APEX trial, which included multiple myeloma patients who had received one to three prior courses of therapy. The Phase II trials that supported Velcade's accelerated approval included a more treatment-experienced population.

Millennium halted the 669-patient APEX trial one year early, in December 2003, after Velcade showed a statistically significant improvement in the primary endpoint of time to progression (TTP) over the comparator arm of high-dose dexamethasone (¹ Pharmaceutical Approvals Monthly Feb. 1, 2004, p. 30).

The firm presented the APEX results in June at the American Society of Clinical Oncology annual meeting. Velcade showed a significant survival advantage (p<0.01) and a 30% reduction in risk of death in the final analysis at one year. An interim analysis found a 58% improvement in TTP in Velcade patients compared to dexamethasone (5.7 months vs. 3.6 months; p<0.001).

Safety was similar between the two groups and to that seen in other Velcade trials. "Importantly, the overall grade four adverse event rates were 11% in the Velcade arm and 13% in the dexamethasone arm," Millennium said.

Also presented at ASCO were results from two small Phase II trials in front-line use. In one of the studies, Velcade in combination with doxorubicin and dexamethasone yielded a 94% response rate. In the other, overall response rate in patients receiving either Velcade alone or in addition to dexamethasone was 79%.

Physicians are "anxious to see the front-line data that was presented at ASCO actually appear in print so that it gives them some justification in using the product front-line," Terifay said. "We do have some physicians anecdotally using the product in front-line but we expect once those published studies appear to see much better adoption in the front-line setting."

Millennium estimates that 45,000 multiple myeloma patients are treated each year. About 25% of those patients are in the "third-line plus" category for which Velcade is currently indicated; another 25% are in the second-line category and the remaining 50% are front-line.

The firm plans to initiate "both company-sponsored and cooperative group Phase III front-line trials in the fourth quarter of 2004 and the first quarter of 2005," President-R&D Robert Tepper, MD, said. "These studies will have multiple comparators and will study both transplant as well as non-transplant eligible patients."

Millennium expects to have roughly 80 trials involving Velcade by the end of 2004. The firm is examining several other areas of oncology, two of the most important being non-Hodgkin's lymphoma and non-small cell lung cancer.

Several Phase II NHL trials are ongoing or slated to begin in 2004. In NSCLC, "our goal for the clinical program is to define the role of Velcade both as a single agent and in combination with other agents," Tepper said.

"The response rates that we see [with] single agent Velcade are in line with other agents that have been approved in NSCLC" - Aventis' Taxotere and AstraZeneca's Iressa - as well as Lilly's Alimta , which is not yet approved for NSCLC, VP-Clinical Development Nancy Simonian, MD, said. "So we think we're in the ballpark."

"We think the future of therapy in lung cancer is going to be in combinations and we're not seeing anything out there that is telling us this is not a place we should be actively pursuing. As part of our overall strategy in lung cancer, we are exploring combinations with all of the new agents that are emerging," Simonian added.

Millennium also reported that it again would not meet its guidance for its market-leading GP IIb/IIIa inhibitor Integrilin (eptifibatide). The firm cited a disappointing "gap between ex-factory sales and demand sales" that "has continued longer than expected. Because Schering-Plough manages product distribution, the company has limited insight into the forces driving this gap, and we are unable to provide a new guidance range at this time."

Millennium had previously projected sales of $320 mil. to $335 mil. for 2004. U.S. ex-factory sales were $71.6 mil. in the second quarter and $67.7 mil. in the first quarter.

"Certainly…things haven't gone perfectly," CEO Mark Levin said in response to analysts' concerns regarding the feasibility of the company's extensive ongoing Integrilin development program. "As we go forward and look at the data, we still continue to believe this will be a $500 mil. product over the next few years and it has a lot to do with our confidence about the PROTECT and REMOVE data coming up in the next few months. It has a lot to do with our EARLY ACS data coming up certainly over the next few years."

Tepper outlined Millennium's two core strategies for Integrilin growth: "In terms of the cath lab strategy, our clinical goal is to demonstrate the superiority of Integrilin use in PCI patients relative to or in combination with other therapies."

Millennium is looking to expand Integrilin into earlier use in acute coronary syndromes, where it sees the greatest market opportunity. "That area is close to 900,000 in total patients and there's a large opportunity there which has not been broken through," Tepper maintained.

The 10,500-patient EARLY ACS trial began enrollment in the second quarter. The trial is looking chiefly at Integrilin's mortality benefit compared to placebo within 96 hours and up to 30 days following randomization. A smaller version of EARLY ACS, MATE-2, began in late 2003 in 820 patients.

Millennium also pointed to its recent European marketing agreement with GlaxoSmithKline as an example of Integrilin's strength. GSK's 180-rep critical care sales force "will actively commercialize Integrilin in Europe upon the approved transfer of marketing authorizations, which is anticipated to be complete by December 2004," the firm said. ¨ ¨