The US Food and Drug Administration (FDA) has finally approved Bristol Myers Squibb’s (BMS) CAR T-cell therapy Breyanzi, previously known as liso-cel, after delaying the decision in November 2020.
The FDA has cleared Breyanzi (lisocabtagene maraleucel) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL).
Breyanzi targets CD19, a protein which is highly expressed on the surface of B cells and which remains there following the transformation of these cells from normal to malignant.
“[This] FDA approval reflects our deep commitment to advancing cell therapy research, developing innovative treatments and supporting patients at every step of their treatment journey,” said Samit Hirawat, chief medical officer of BMS.
In February 2020, the FDA began a priority review of Breyanzi in LBCL, but later delayed its decision on the CAR T therapy after it was unable to complete an inspection of a third-party manufacturing facility in the US, which is involved in making a component of the treatment.
The FDA said it was unable to conduct the inspection due to travel restrictions related to the COVID-19 pandemic.
BMS acquired Breyanzi following its $74bn takeover of Celgene in 2019 – the CAR-T therapy is one of the key assets critical to the potential payout of the merger in contingent value rights (CVR).
As part of the merger agreement, BMS agreed to make a series of conditional payments of an extra $6bn to former Celgene shareholders or CVR holders, contingent upon the CAR T therapy receiving regulatory approval by 31 December 2020.
Breyanzi joins other approved CAR T therapies on the market from Gilead/Kite and Novartis.
Gilead/Kite’s Yescarta (axicabtagene ciloleucel) was the first FDA-approved CAR T therapy for the treatment of adult patients with relapsed or refractory LBCL, including DLBCL.
Novartis’ Kymriah (tisagenlecleucel) was approved soon afterwards, also gaining clearance for the treatment of relapsed/refractory diffuse large B-cell lymphoma.
BMS, Novartis and Gilead/Kite’s respective CAR T therapies all carry a black box warning for neurotoxicity, as well as cytokine release syndrome – an overreaction of the body’s immune system – which is common in patients receiving this type of therapy.
BMS will not only have to contend with Novartis and Gilead/Kite’s rival products, but also with the COVID-19 pandemic, and this is likely to impact the treatment process for Breyanzi, as patients need to receive regular transfusions in a hospital.