Millennium: The Takeda Oncology Company with its parent company, Takeda Pharmaceutical Company Limited, has announced that the U.S. Food and Drug Administration (FDA) has approved VELCADE® (bortezomib) for the retreatment of adult patients with multiple myeloma (MM) who had previously responded to VELCADE therapy and relapsed at least six months following completion of prior VELCADE treatment. The labeling update includes dosing guidelines as well as safety and efficacy findings for the use of VELCADE as a single agent or VELCADE in combination with dexamethasone in patients previously treated with VELCADE. VELCADE retreatment may be started at the last tolerated dose.

The approved retreatment sNDA consisted of a Phase 2 study and other supportive data. The Phase 2 international RETRIEVE trial showed a 38.5 percent overall response rate (ORR) in multiple myeloma patients who had been previously treated with a VELCADE-based regimen (median of two prior lines of therapy) and had previously achieved a partial response or better. The safety profile seen with VELCADE retreatment was consistent with the known safety profile of intravenous VELCADE in relapsed multiple myeloma; no cumulative toxicities were observed upon retreatment. The most common adverse drug reaction was thrombocytopenia, which occurred in 52 percent of the patients.

“For the past 11 years, VELCADE has played an important role as the only therapy proven to extend overall survival for patients with newly diagnosed and relapsed multiple myeloma,” said Michael Vasconcelles, MD, Global Head, Oncology Therapeutic Area Unit, Takeda. “With these newly approved dosing guidelines, physicians will be able to provide their patients, who have previously received VELCADE, with an effective treatment extending VELCADE use across the continuum of care of multiple myeloma.”

RETRIEVE was a single arm, open-label trial. The study enrolled 130 patients ages 18 years and older who had previously responded to VELCADE-based therapy and relapsed at least six months after prior treatment with VELCADE. The study met its primary endpoint of best confirmed response to retreatment as assessed by European Group for Blood and Marrow Transplantation (EBMT) criteria.
•Patients had received a median of two prior therapies (range of 1-7).
•Dexamethasone was administered in combination with VELCADE in 94 patients.
•Of the 130 patients, one patient achieved complete response and 49 achieved partial response (50/130; ORR 38.5 percent).
•In the 50 responding patients, the median duration of response was 6.5 months (range of 0.6 to 19.3 months).
•The incidence of grade ≥3 thrombocytopenia was 24 percent. Peripheral neuropathy occurred in 28 percent of patients, with the incidence of grade ≥3 peripheral neuropathy reported at 6 percent. The incidence of serious adverse reactions was 12.3 percent; the most commonly reported serious adverse reactions were thrombocytopenia (3.8 percent), diarrhea (2.3 percent), herpes zoster and pneumonia (1.5 percent each). Adverse reactions leading to discontinuation occurred in 13 percent of patients.