Monday, December 12, 2011

Millennium reports myeloma drug advances, updates drug recalls

By Lori Valigra, Mass High Tech correspondent

Cambridge cancer pharmaceutical company Millennium: The Takeda Oncology is reporting advances in its drugs for multiple myeloma, and said it is adding manufacturing suppliers in the wake of a series of precautionary recalls for its Velcade treatment in the United States and Europe.

The company issued recalls for Velcade in the United States last week and in November 2010. And in November 2011, the European Medicines Agency recommended a recall for partner Johnson & Johnson’s Velcade in Europe. The reason for the recalls is potential contamination risks found at contract manufacturer Ben Venue Laboratories in Bedford, Ohio.

Millennium CEO Deborah Dunsire told Mass High Tech that the European Medicines Agency and the U.S. Food and Drug Administration (FDA) had sufficient question marks about the full control of production at all times at the plant, so Millennium decided to voluntarily pull the drug.

“We have two other suppliers, so there will be no interruption in the supply,” she said, adding that the company has been increasing the supply of Velcade from the other suppliers for a period of time and will continue to ramp up the quantities from the most recent supplier, which was approved by the FDA in March.

The Ohio facility, which Dunsire described as old, had told Millennium two months ago that it would discontinue as a manufacturer of the drug in two years. “If Johnson & Johnson is able to more quickly convert countries where only the Ohio manufacturer has been approved, then we will accelerate our move to the other suppliers,” Dunsire said. “We’re also looking for another company so we’d have three suppliers.”

She said there were few concerns expressed by doctors over the recalls. “Despite subliminal concern, every vial released from that factory goes through post-production quality checking,” she said, adding that there was no evidence of contamination.

The company continues to increase the uses of Velcade both by cancer type and by indication. At the American Society of Hematology (ASH) meeting today in San Diego, Calif., Millennium is releasing a new five-year follow up of overall survival data on Velcade demonstrating a significant impact on extending the lives of multiple myeloma (MM) patients.

The data show that Velcade-based therapy resulted in a statistically significant 13.3 month increase in the median chance of survival across all MM patient subgroups, including those 75 years and older, and a 31 percent reduced risk of death. The data also suggest that Velcade should be given first for newly diagnosed, previously untreated MM patients, as those who received Velcade as first line treatment in the trial showed greater chance of survival than those who received it or other therapies in subsequent treatments during the five year follow-up.

“The excitement for patients here is there are now therapies that extend their lives,” Dunsire said. “It’s best to use this first. It truly makes a different in outcomes.”

She added that the five-year data give doctors more confidence to use the drug. Velcade currently is used in close to 60 percent of all frontline MM treatments, she said. “We’re more confident that more and more eligible patients will receive Velcade,” she said. Patients received Velcade intravenously along with melphalan and prednisone, and were compared to patients taking melphalan and prednisone alone.

The company also said the study data showed no association between Velcade-treated patients and the development of additional, new cancers, so-called secondary primary cancers. Additional data examined Velcade as a maintenance therapy.
 
In addition, the company tomorrow plans to release early data on MLN9708, a new oral proteasome inhibitor for patients with relapsed and/or refractory multiple myeloma. To date, Velcade has been given by drip, and more recently, it has been given subcutaneously in studies. “Our scientists discovered a way to make an oral proteasome inhibitor, a new drug called MLN9708 that has a different side effect profile, Dunsire said. “In early trials it has demonstrated encouraging effectiveness and a lesser side-effect profile,” she said.

Millennium has been moving to extend the uses of Velcade. In April, it submitted two supplemental new drug applications (NDAs) for Velcade to the FDA.

The first NDA sought to add subcutaneous administration for Velcade, and the second is for a combination with rituximab in patients with relapsed follicular non-Hodgkin lymphoma. The drug currently is approved for intravenous use in patients with multiple myeloma and those with mantle cell lymphoma.

Dunsire said Millennium has a meeting scheduled with the FDA on Jan. 23 regarding the positive results for the subcutaneous Velcade, as it showed patients saw a two-thirds decrease in peripheral neuropathy, which is both a side effect of Velcade and a normal side effect of MM. “The subcutaneous Velcade is more convenient and it is physically possible to give it to more patients,” she said, noting that cancer patients undergoing chemotherapy may not have blood vessel access for drugs.

The second NDA has been withdrawn, she said, because Millennium did not believe its benefit was sufficient enough.

While Dunsire said Millennium has significant existing capacity to handle wider sales and use of Velcade, it is increasing staff for other molecules under development. It expects to hire around 30 people in Cambridge in clinical research, regulatory affairs and clinical operations.