multiple myeloma
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has advised the European Commission not to approve ixazomib (Ninlaro), an oral proteasome inhibitor, as a treatment for patients with relapsed and/or refractory multiple myeloma (MM).
Takeda Pharmaceutical Company Limited, the company developing ixazomib, said it intends to appeal this opinion and request a re-examination by the CHMP.
“We are disappointed by the CHMP’s opinion,” said Christophe Bianchi, MD, president of Takeda Oncology. “With the support of European key medical experts, we will continue our efforts working closely with the CHMP to make Ninlaro—the first oral proteasome inhibitor—available for patients in Europe.”
“We stand behind the TOURMALINE-MM1 trial data, which were recently published in the New England Journal of Medicine and demonstrated a significant extension in progression-free survival for Ninlaro plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone and a favorable benefit-risk profile.”
TOURMALINE-MM1
The trial enrolled 722 patients with relapsed (77%), refractory (11%), relapsed and refractory (12%), or primary refractory (6%) MM.
The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362). Baseline patient characteristics were similar between the treatment arms.
The study’s primary endpoint was progression-free survival, which was significantly longer in the IRd arm than the Rd arm. The median progression-free survival was 20.6 months and 14.7 months, respectively. The hazard ratio was 0.74 (P=0.01).
At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.
Adverse events (AEs) occurred in 98% of patients in the IRd arm and 99% in the Rd arm. Grade 3 or higher AEs occurred in 74% and 69% of patients, respectively; serious AEs occurred in 47% and 49%, respectively; and on-study deaths occurred in 4% and 6%, respectively.
Grade 3 and 4 thrombocytopenia, rash, and gastrointestinal AEs were more frequent in the IRd arm than the Rd arm.
The incidence of peripheral neuropathy was similar in the 2 arms, as was the percentage patients who developed new primary malignant tumors.
