The FDA granted Roche Holding AG's Genentech Inc. accelerated approval for Polivy (polatuzumab vedotin), a first-in-class anti-CD79b antibody-drug conjugate, to be taken with bendamustine and Rituxan (rituximab) for adults with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL). The medicine, approved for those who have received at least two prior therapies, got a go-ahead based on complete response rates observed in a randomized, controlled trial. The FDA said it is the first chemoimmunotherapy regimen for the indication.

"Despite meaningful progress in the treatment of diffuse large B-cell lymphoma, treatment options are very limited when the disease is refractory to or recurrent after multiple regimens," said Sandra Horning, Genentech's chief medical officer and head of global product development.

DLBCL is the most common form of non-Hodgkin lymphoma and is generally responsive to first-line treatment. But as many as 40% of patients will relapse, at which time salvage therapy options are limited and survival is short, Genentech said. In the U.S., about 25,000 new cases of DLBCL are expected to be diagnosed this year.

Polivy is expected to be available to patients immediately and will priced at about $90,000, which covers a fixed course of about four months, with dosing every three weeks for six cycles. Cost will vary to some degree, though, because dosing is weight-based. The Rituxan element of therapy will cost about $39,500 over the course of the four-month regimen, while bendamustine's cost will vary depending on its source.

The green light is Genentech's sixth FDA approval in the last six months, and its fifth blood cancer medicine to gain approval, the company said.

Polivy employs an anti-CD79b antibody conjugated to the tubulin polymerization inhibitor monomethyl auristatin E developed using Seattle Genetics Inc.' antibody-drug conjugate technology, an approach thought to minimize the effects on normal cells. The drug is also being investigated for the treatment of several types of non-Hodgkin lymphoma.

The FDA's approval in r/r DLBCL was based on the results from the phase Ib/II GO29365 study, which Genentech said was the first and only randomized pivotal trial to show higher response rates over bendamustine plus Rituxan (BR), a commonly used regimen in people with r/r DLBCL who are ineligible for a hematopoietic stem cell transplant. Results of the study showed that 40% of people treated with Polivy plus BR achieved a complete response (95% CI: 25-57), meaning no cancer could be detected at the time of assessment, compared to 18% with BR alone (95% CI: 7-33). Complete response rates were assessed by independent review committee.

The study also showed that 45% of people on Polivy plus BR achieved an objective response at the end of treatment (95% CI: 29-62), compared to 18% of people treated with BR alone (95% CI: 7-33). Among trial participants treated with Polivy plus BR who achieved a complete or partial response, 64% had a duration of response (DOR) lasting at least six months vs. 30% of people treated with BR alone. Additionally, 48% of people treated with Polivy plus BR had a DOR lasting at least a year as compared to 20% of people treated with BR alone.

Adverse reactions occurring in at least 20% of patients, and at least 5% more frequently in patients treated with Polivy plus BR compared to BR alone, included low white blood cell count, low platelet levels, low red blood cell count, numbness, tingling or pain in the hands and feet, diarrhea, fever, decreased appetite and pneumonia.

Continued approval of Polivy for the indication is, as is typically the case with drugs securing accelerated approval, contingent upon verification and description of clinical benefit in a confirmatory trial.

In addition to its priority review, Polivy was recognized as a breakthrough therapy by the FDA and has landed a PRIME designation from the EMA.

Other medicines approved for the treatment of r/r DLBCL include the CAR T-cell therapies Yescarta (axicabtagene ciloleucel, Gilead Sciences Inc.) and Kymriah (tisagenlecleucel, Novartis AG). (See BioWorld, Oct. 20, 2017.)