This section provides a brief overview of new cancer drugs or new indications approved by the FDA between November 14 and November 21, 2019.
On November 14, 2019, the FDA granted accelerated approval to zanubrutinib (Brukinsa; BeiGene) for the treatment of patients with mantle-cell lymphoma who have received ≥1 previous therapies.
“Mantle-cell lymphoma usually responds well to initial treatment, but eventually returns or stops responding, and the cancer cells continue to grow. This is a life-threatening condition,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Clinical trials showed that 84% of patients saw tumor shrinkage with this therapy. For patients whose disease relapses or becomes refractory, secondary therapies may be successful in providing another remission, and today’s approval will provide patients with another treatment option,” he said.
The efficacy of zanubrutinib was assessed in 2 clinical trials. In the phase 2, multicenter, single-arm BGB-3111-206 trial, 86 previously treated patients with relapsed or refractory mantle-cell lymphoma who had ≥1 previous therapies received 160 mg of zanubrutinib orally twice daily until disease progression or unacceptable toxicity. In the phase 1/2, dose-escalation, multicenter, single-arm BGB-3111-AU-003 trial of B-cell malignancies, 32 previously treated patients with mantle-cell lymphoma received 160 mg of zanubrutinib orally twice daily or 320 mg once daily.
The primary efficacy end point in both trials was overall response rate as assessed by an Independent Review Committee. In the BGB-3111-206 trial, the overall response rate was 84% (95% confidence interval [CI], 74-91), with a complete response rate of 59% (95% CI, 48-70) and a median response duration of 19.5 months (95% CI, 16.6-not estimable). In the BGB-3111-AU-003 trial, the overall response rate was 84% (95% CI, 67-95), with a complete response rate of 22% (95% CI, 9-40) and a median response duration of 18.5 months (95% CI, 12.6-not estimable).
The most common (≥20%) adverse reactions in patients treated with zanubrutinib included decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, and cough. Serious adverse reactions were reported in 31% of patients. The most frequent serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients.
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On November 15, 2019, the FDA approved crizanlizumab (Adakveo; Novartis) to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients aged ≥16 years with sickle-cell disease.
The FDA approval of crizanlizumab was based on data from the randomized, double-blind SUSTAIN clinical trial of 198 patients with sickle-cell disease who have had 2 to 10 VOC episodes in the 12 months before study enrollment. The primary efficacy end point in the trial was the annual rate of VOCs leading to a healthcare visit.
Patients were randomized to receive crizanlizumab 5 mg/kg (N = 67), crizanlizumab 2.5 mg/kg (N = 66), or placebo (N = 65) administered intravenously in week 0, week 2, and every 4 weeks thereafter. Total treatment duration was 52 weeks.
Results showed that treatment with crizanlizumab significantly lowered the median annual rate of VOCs compared with placebo (1.63 vs 2.98; P = .01). Median time to first VOC from randomization was 4.1 months with crizanlizumab and 1.4 months with placebo.
The most common (>10%) adverse reactions in patients receiving crizanlizumab were nausea, arthralgia, back pain, and pyrexia.
On November 21, 2019, the FDA approved acalabrutinib (Calquence; AstraZeneca) as initial or subsequent therapy for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This is the second approval under Project Orbis, a collaboration between the FDA, the Australian Therapeutic Goods Administration, and Health Canada.
“Today, as part of a US, Australian, and Canadian collaboration known as Project Orbis, the US approved a new treatment option for those living with chronic lymphocytic leukemia or small lymphocytic lymphoma. The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international partners,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “We are pleased to continue working alongside our Australian and Canadian colleagues to facilitate new treatment options for patients, and the FDA looks forward to working with other countries in future application reviews.”
The FDA also used the Real-Time Oncology Review pilot program when it reviewed the application for acalabrutinib, a process designed to streamline the submission of data before the completion of the entire drug application.
The agency based its supplemental approval on data from the interim analyses of 2 phase 3 randomized clinical trials (ELEVATE-TN and ASCEND) that compared acalabrutinib as monotherapy or in combination with obinutuzumab in patients with CLL. In both trials, progression-free survival was longer with alabrutinib treatment versus other standard therapies.
The most common (≥20%) adverse events associated with acalabrutinib include anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, bruising, and myalgia.
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