FDA approves Roche’s second CD20xCD3 bispecific in certain lymphomas

The FDA granted accelerated approval to Genentech’s CD20xCD3 bispecific for patients with a certain type of non-Hodgkin’s lymphoma on Thursday night, as the Roche unit and Genmab promote different benefits to their potentially competitive medicines.

Genentech’s Columvi and AbbVie/Genmab’s Epkinly, which was greenlit last month, are now approved as third-line treatments for relapsed or refractory diffuse large B-cell lymphoma, which is the most common form of non-Hodgkin’s lymphoma in the US.

The drugmakers are touting the differences in their CD20xCD3 bispecifics: Columvi is meant to be given for a set period of about 8.5 months, whereas Epkinly, which is delivered under the skin, is administered until the disease progresses or it can’t be tolerated any longer. Columvi is an intravenous infusion, though Genentech is also testing a subcutaneous version in early-stage studies.

Ginna Laport

“The more options there are for patients, the better,” Ginna Laport, Genentech VP and global head of NHL/CLL development, told Endpoints News in an interview.

As a third-line treatment, the estimated price of Columvi is $350,000 — for 13 infusions over 8.5 months, a spokesperson told Endpoints via email. Genmab has said its drug has a monthly list price of $37,500, putting the annual price at $450,000.

Columvi will be made available in the US “in the coming weeks,” a Genentech spokesperson said. Laport said the drug is expected to get a European endorsement this month. It was approved in Canada earlier this year.

The FDA based its priority decision on data from a Phase I/II study in which 56% of patients given the fixed-duration drug responded to treatment, representing 74 of 132 people. Out of those 74, 57 completely responded, meaning investigators could not detect signs or symptoms of cancer. The responses lasted for at least nine months in two-thirds of the responders, Genentech said. The data, published in the New England Journal of Medicine, showed the median duration of response to be 1.5 years.

People with the diffuse large B cell lymphoma “may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” Krish Patel, an investigator for the Columvi trial and director of the Swedish Cancer Institute’s lymphoma program in Seattle, said in a statement.

Genentech hopes to move quickly from an accelerated nod to a full approval. The pharma has already completed enrollment in the confirmatory study and plans to deliver data on the trial this year, Laport said. Genentech is also activating clinical trial sites for a Phase III study of Columvi in another indication, testing whether the drug is better than chemotherapy at treating patients with mantle-cell lymphoma. The first patient is set to be dosed later this year, she said.

Genentech said the most common adverse event was cytokine release syndrome (CRS), in which the immune system goes into overdrive. About 70% of patients in the study experienced CRS. Musculoskeletal pain, fatigue and rash were experienced by about one-fifth of the patients.

Before patients receive Columvi, they get a single dose of the cancer drug obinutuzumab (marketed by Genentech as Gazyva) one week in advance. They’ll also get a corticosteroid, fever-reducing medicine and an antihistamine to help reduce the risk of CRS, Genentech said.

Genentech now has two FDA-approved CD20xCD3 bispecifics: Columvi, and Lunsumio, a third-line treatment for adults with relapsed or refractory follicular lymphoma. The pharma was the first to secure a win in the drug class last December when the FDA gave a thumbs up to Lunsumio. Regeneron and Xencor are also developing treatments in the CD20xCD3 field.

Columvi is expected to be a more potent therapy than Lunsumio, Laport said; Columvi has two arms to latch onto CD20, and Lunsumio has one. Both drugs were created in-house, with the Swiss pharma developing Columvi and its California-based Genentech unit originating Lunsumio.

Columvi’s name is a combination of “co” for co-opting both T and B cells to drive cancer-killing effects; “lum” for lumen or light; and “vi” for “victory,” a spokesperson said.

Biogen has a chance at nabbing tiered royalties on the drug’s net sales in the US as part of its longstanding collaboration with Genentech.

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