Game on, AbbVie. Roche's Columvi nabs FDA nod as 2nd bispecific for large B-cell lymphoma

Less than a month after AbbVie and Genmab won FDA approval for Epkinly, Roche has crossed the finish line with its bispecific answer to large B-cell lymphoma.

The FDA has granted accelerated approval to Roche’s Columvi, or glofitamab, to treat diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma arising from follicular lymphoma in patients who’ve tried at least two prior lines of systemic therapy, Roche’s Genentech announced Thursday.

The decision comes two weeks ahead of an already shortened priority review timeline and puts Columvi on deck to challenge Epkinly. Both drugs are CD20xCD3 bispecific T-cell engagers.

But Columvi’s approval is narrower than its rival’s. For some reason, the Roche drug’s label doesn’t include language on high-grade B-cell lymphoma despite a 7% representation of those patients in its phase 2 trial. Still, DLBCL is the much larger indication.

In the impending rivalry, AbbVie and Genmab’s Epkinly boasts a convenience edge as an under-the-skin injection. For now, Columvi is an intravenous infusion, although Roche is studying the drug in a subcutaneous formulation.

To Ginna Laport, Genentech’s global head of lymphoma and chronic lymphocytic leukemia development, Columvi’s biggest differentiator is its fixed duration of treatment.

Compared with treatment until progression, the fixed duration approach “allows patients for treatment-free interval, [and] it decreases the chance of long-term side effects,” Laport said in an interview on the sidelines of the recent American Society of Clinical Oncology annual meeting.

In the phase 2 trial that supported Columvi’s approval, 68% of patients who had previously achieved no sign of cancer remained in complete remission at 18 months, according to an update shared at ASCO. At the American Society of Hematology annual meeting in December, investigators reported that two patients with progressive disease have been retreated with Columvi. Both gained complete responses.

Those are encouraging signs that Columvi’s effect is durable despite patients stopping treatment after 8.5 months. But researchers have said that longer follow-up after the end of treatment is still needed.

AbbVie and Genmab’s Epkinly used to have arguably the best efficacy data, but Columvi appears to be catching up.

Columvi’s FDA label shows that the Roche drug triggered a response in 56% of 132 patients of DLBCL or LBCL arising from follicular lymphoma, with 43% being complete responses. The median duration of response was 18.4 months.

By comparison, Epkinly boasts a 61% overall response rate in its own trial of 148 patients, including 38% of patients who had a complete response. The median duration of response was 15.6 months. Compared with the Columvi trial, Epkinly’s study had a higher percentage of patients who had previously tried a CAR-T therapy.

On the safety front, both drugs are both linked to cytokine release syndrome because they’re designed to augment the immune system. Columvi recorded a 70% CRS rate, including 4.1% at grade 3 or 4. CRS occurred in 51% of patients receiving Epkinly in its own trial, including 2.5% at grade 3.

For Columvi, patients are given a corticosteroid, a fever-reducing med and an antihistamine as premedications to reduce the risk of CRS.

An accelerated approval means Roche still needs to provide confirmatory data. The company is running the phase 3 STARGLO trial comparing the combination of Columvi and chemotherapy with a Rituxan-chemo combo in second-line DLBCL patients who are ineligible for stem cell transplant.

Columvi is Roche’s second CD20xCD3 T-cell engager to reach the market. The FDA in December cleared the company’s Lunsumio, which also features a fixed duration of treatment, as a third-line therapy for follicular lymphoma.

In DLBCL, Roche recently won a hard-fought FDA go-ahead for its antibody-drug conjugate Polivy as part of a first-line therapy. The Swiss pharma is investigating combining Lunsumio with Polivy in second-lien DLBCL in the SUNMO trial.