FDA Action Alert: GBT’s Oxbryta and BeiGene’s Brukinsa
The U.S. Food and Drug Administration (FDA) has a quiet end of the month, particularly since the two remaining PDUFA dates were decided in November 2019. Here’s a look at the two drugs that had dates this week but were approved early and are now on the market.
GBT’s Oxbryta for Sickle Cell Disease
Global Blood Therapeutics (GBT) had a target action date of February 26, 2020, for its New Drug Application (NDA) for voxelotor for sickle cell disease (SCD). It was under Priority Review. On November 25, 2019, the FDA approved voxelotor, under the brand name of Oxbryta, for SCD in adults and children 12 years of age and older. It is the first oral therapy taken once a day that inhibits sickle hemoglobin polymerization, the root cause of the disease.
SCD is a lifelong inherited blood disorder caused by a genetic mutation in the beta-chain of hemoglobin. This leads to abnormal hemoglobin called sickle hemoglobin (HbS). In its deoxygenated form, HbS tends to polymerize, or bind together, causing long rigid rods inside a red blood cell. This deforms the red blood cells into the well-known sickle shape, causing it to become inflexible, causing hemolytic anemia, which is to say, low hemoglobin as the result of RBC destruction. It can lead to multi-organ damage and early death.
The drug acts by increasing hemoglobin’s affinity for oxygen. Voxelotor blocks polymerization and the resultant sickling and destruction of RBCs.
At the time of approval, Ted W. Love, president and chief executive officer of GBT, said, “Today is a major milestone not only for GBT but, most importantly, for people living with SCD, their families and those who care for them. When we started our journey with the SCD community more than eight years ago, we set out to transform the way this devastating, lifelong disease is treated. We are proud to bring this breakthrough therapy to the SCD community. Uniquely developed from inception to treat SCD, Oxbryta embodies GBT’s commitment to develop and deliver innovative medicines for patients with overlooked, life-limiting chronic diseases. We are grateful to the patients, caregivers, clinical trial investigators, healthcare providers and advocates who have worked alongside us to develop this first-in-class therapy.”
BeiGene’s Zanubrutinib for Mantle Cell Lymphoma
BeiGene, headquartered in Beijing, China and Cambridge, Massachusetts, had a target action date of February 27 for its NDA for zanubrutinib for patients with mantle cell lymphoma (MCL) who have received at least one previous therapy. It was granted Priority Review. On November 14, 2019, the FDA also approved the drug, with the brand name Brukinsa.
Zanubrutinib is a potent and selective BTK inhibitor designed to maximize BTK occupancy and minimize off-target effects. The NDA included data from the global Phase I/II trial in patients with B-cell lymphomas and an aggregate of 123 patients in the multicenter Phase II trial in patients with relapsed or refractory (rr) MCL in China, as well as safety data on 641 patients from five clinical trials.
Lymphoma is a diverse family of cancers that originates from B-, T- or NK- cells. MCL is an aggressive form of non-Hodgkin lymphoma (NHL) that comes from B-cells originating in the “mantle zone.”
“Mantle cell lymphoma usually responds well to initial treatment, but eventually returns or stops responding, and the cancer cells continue to grow,” said Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, at the time. “Clinical trials showed that 84% of patients saw tumor shrinkage with this therapy. For patients whose disease relapses or become refractory, secondary therapies may be successful in providing another remission, and today’s approval will provide patients with another treatment option.”
On December 8, 2019, the company presented clinical data from three trials of Brukinsa at the 61st American Society of Hematology (ASH) Annual Meeting held in Orlando, Florida. Two oral presentations were in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), where it showed consistent safety and a high overall response rate (ORR). In a poster, it presented data on Brukinsa combined with its own anti-PD-1 checkpoint inhibitor tislelizumab in patients with previously treated B-cell malignancies. It also showed preliminary efficacy and was generally well tolerated.