With hard-fought Polivy approval, Roche looks to shake up decades of established practice in lymphoma

After a regulatory scare, Roche can now kick off work on changing nearly 20 years of clinical practice for the treatment of diffuse large B-cell lymphoma (DLBCL).

The FDA has signed off on Roche’s Polivy as part of a five-drug combination for previously untreated DLBCL or high-grade B-cell lymphoma, the Swiss pharma giant said Wednesday.

The new regimen is the first new treatment in nearly 20 years to significantly improve outcomes in first-line DLBCL, according to Roche. Analysts have previously said the front-line use could add $2 billion to Polivy’s peak sales.

But after the FDA laid bare some of its reservations about the company’s application, it’s still unclear to what degree Polivy will be able to challenge the standard R-CHOP therapy.

For this approval, Polivy made its case in the phase 3 POLARIX trial, which showed that Polivy and R-CHP reduced the risk of progression or death by 27% compared with R-CHOP. With the new regimen, Roche is replacing the Oncovin (O) component in R-CHOP with Polivy, an antibody-drug conjugate.

During an internal review, the FDA suggested the tumor progression benefit was “modest.” And the agency appeared not so confident in Polivy because it has yet to show an ability to extend patients’ lives despite a longer time of trial follow-up.

The FDA also picked apart POLARIX’s data in different patient subgroups. The FDA’s analysis found that the high-grade B-cell lymphoma patients appeared to have driven the majority of the progression-free survival improvement, whereas patients with DLBCL, the largest subgroup, saw limited benefit.

Still, during an advisory committee meeting in March, an external panel of oncology experts voted 11 to 2 in support of a favorable benefit-risk profile for Polivy as a front-line lymphoma treatment.

Most experts argued that Polivy should be approved given that POLARIX is indeed a positive trial and that the new combo’s ability to stave off progression represents a win for patients because it may save them from further treatment.

As for overall survival, Roche, the FDA advisers and agency staffers all recognized that the existing R-CHOP regimen is already very powerful. This means POLARIX may never see a clear overall survival signal.

Several members of the FDA advisory committee said that the POLARIX results may not be the major breakthrough that they were looking for.

“I would consider this regimen to be an option, rather than a standard,” Greg Nowakowski, M.D., from the Mayo Clinic, said of Polivy. “In a setting of lack of overall survival difference from R-CHOP, I would consider them equivalent.”

But Roche already has one tailwind for adoption. The National Comprehensive Cancer Network recently included Polivy as a category 1—the highest level—preferred regimen for first-line DLBCL.

Wednesday’s go-ahead also converted an accelerated approval for Polivy in combination with Rituxan and bendamustine as a third-line treatment for DLBCL into a full approval.

Hoping to further improve treatment outcomes in DLBCL, Roche is combining Polivy with its CD20xCD3 bispecific antibody Lunsumio in the phase 3 SUNMO study in previously treated disease.