Millennium Pharmaceuticals, Inc. announced that the US Food and Drug Administration (FDA) granted Priority Review designation to its supplemental new drug application (sNDA) for Velcade for the treatment of relapsed mantle cell lymphoma (MCL), an aggressive, incurable subtype of non-Hodgkin's lymphoma (NHL) for which there is no current standard of care.
Priority Review is granted to a pharmaceutical compound that addresses an unmet medical need and would be a significant improvement in treatment compared to existing therapies. The FDA expedites the approval process for such a sNDA and targets a decision by six months. Acceptance of the filing indicates the FDA has determined that the sNDA is sufficiently complete to permit a substantive review.
"Receiving Priority Review is a significant step forward in accelerating and expanding the potential of Velcade in cancers beyond multiple myeloma," said Deborah Dunsire, M.D., president and CEO, Millennium. "Our mantle cell lymphoma application, for which we can expect a decision from the FDA by December 9, 2006, is the first step in an advanced NHL development programme exploring the use of Velcade in this large and growing patient population in need of new treatment options."
The sNDA submission was based on final phase II data from the Pinnacle study, one of the largest multi-centre studies in relapsed MCL to date, which showed a 33 percent overall response rate and an 8 percent complete response rate. Importantly, the median duration of response was 9.2 months, and 13.5 months in patients who achieved a complete response. These results are similar to those of four investigator initiated Phase II clinical trials where overall response rates of 30 to 40 per cent with single-agent Velcade were established.
In the prospective, single-arm study, 155 patients with relapsed or refractory MCL with a maximum of two prior therapies, received single-agent Velcade 1.3mg/m2 twice weekly for two weeks every 21 days for up to one year. Patients achieving complete response, unconfirmed complete response or partial response received a median of eight treatment cycles, and all patients in the study received a median of four cycles. Study results included: Overall response rate of 33 per cent; Complete response rate of 8 per cent; Median duration of response of 9.2 months; 13.5 months in patients achieving a complete response; Median time to progression of 6.2 months; Median treatment-free interval of 13.8 months in patients achieving a complete response.
Treatment was well tolerated. The most common non-haematologic adverse events were fatigue, gastrointestinal events and peripheral neuropathy. Haematologic toxicities were mild to moderate and consistent with those previously seen with Velcade.
Velcade is approved by the FDA for the treatment of multiple myeloma patients who have received at least one prior therapy and is the market leader in relapsed multiple myeloma with over 44,000 patients treated worldwide including clinical trials. Earlier this year, Millennium and co-development partner, Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD), initiated a phase III, randomized clinical trial with Velcade in combination with rituximab in patients with relapsed or refractory follicular lymphoma, a common subtype of non-Hodgkin's lymphoma.