Takeda has claimed victory with midstage study results for one of the most important experimental meds in its pipeline of cancer drugs, MLN9708, a potential successor to its blockbuster oncology product Velcade. And the program has already advanced to Phase III trials as Takeda's Millennium oncology unit seeks its next multibillion-dollar drug.
Today Millennium highlighted upbeat results from the mid-stage portion of a 65-patient Phase I/II study for a combo therapy based on its oral proteasome inhibitor MLN9708 for patients with multiple myeloma, a cancer of the plasma cells now treated with Velcade and other drugs. The NIH's National Cancer Institute projects 21,700 new cases of the relatively rare cancer and 10,710 deaths from it this year.
The ongoing study treated newly diagnosed patients with 9708 in combination with the approved oral meds Revlimid from Celgene ($CELG) and dexamethasone. Of 52 patients treated in the Phase II portion of the trial, more than half or 58% had at least a 90% reduction in myeloma proteins in their blood, nailing the primary goal of the study, according to Millennium. The cancer went into remission in nearly a quarter of those patients, with complete responses reported for 23% of patients.
Millennium is touting the results today at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta. Based on the results of early studies, Millennium jumped into Phase III clinical trials with 9708 this year in patients with more advanced forms of multiple myeloma and AL amyloidosis. And the company aims to begin late-stage study of the drug as a first line of attack against multiple myeloma next year, Deborah Dunsire, Millennium's CEO, told FierceBiotech in an interview.
MLN9708 is the first oral proteasome inhibitor to hit human trials. Velcade is an injected proteasome inhibitor, and patients must go to clinics to be treated with the drug. MLN9708 holds the promise of blocking the proteasome--which regulates proteins that enable myeloma and other cells to thrive--in a more convenient weekly oral dose. It could also reduce risk of nerve damage known as peripheral neuropathy that is associated with Velcade.
High levels of peripheral neuropathy generally afflict about 16% of patients on an IV version of Velcade and 6% in patients on injections of the drug, Dunsire said. "With 9708 we're seeing a much lower rate of peripheral neuropathy at all and then very, very few [cases] that are higher-grade," she said, "and that's very encouraging."
In the study, two patients suffered a higher-grade or grade-three peripheral neuropathy, with milder cases of the nerve damage affecting 15 of 17 people who experienced the side effect. One patient died of pneumonia in the trial. Patients also suffered from fatigue, nausea, vomiting, diarrhea, rashes, decreased blood counts and electrolyte changes. Seven patients dropped out because of side effects.
On MLN9708 rests a big part of Takeda's future myeloma franchise. Takeda and its partner Johnson & Johnson ($JNJ) generate more than $2 billion in annual sales of Velcade, which is due to lose patent exclusivity in the U.S. in 2017 and in Europe in 2019, Dunsire said. MLN9708 could be ready for the market in late 2015 for relapsing and refractory forms of multiple myeloma.
Takeda has invested heavily in making oncology one of several growth areas as the drugmaker deals with the loss of patent protections for its faded blockbuster diabetes drug Actos. It acquired Velcade, the company's best-selling cancer drug, in its $8.9 billion buyout of Millennium in 2008.
"It's very exciting to be the first in a therapeutic area [and] in a class as we have been with Velcade," Dunsire said in an interview. "But then to be able to say, 'How do we make this better?' and bring a product like 9708 forward is tremendously exciting."
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