- Roche on Monday won an early approval for its blood cancer drug Polivy, securing an OK from the Food and Drug Administration for use in a type of lymphoma after just four months of regulatory review.
- Polivy is an antibody-drug conjugate, a type of cancer treatment that links a toxic chemotherapy with an antibody capable of targeting specific proteins on the surface of cells. Decades of research into the technology, however, have yielded approvals for only five other such drugs.
- The FDA cleared Polivy for use in patients with diffuse large B-cell lymphoma whose cancers had either relapsed or become resistant to previous therapies. By the drug's label, Polivy could challenge CAR-T cell therapy as a treatment for the cancer type, although physicians recently surveyed by the investment bank Cowen view Polivy as a "bridge" to treatment with CAR-T.
Approval of Polivy (polatuzumab vedotin) comes as antibody-drug conjugates, or ADCs, are enjoying somewhat of a resurgence among drugmakers.
Long the calling card of Seattle Genetics, ADC technology was the focus of AstraZeneca's recent $7 billion deal for a Daiichi Sankyo cancer therapy, and analysts at Cowen see "significant potential" for further dealmaking in the field.
By linking chemotherapy to a targeted antibody, ADCs promise similar cancer-killing efficacy but less systemic exposure than chemo can offer alone.
Polivy, for example, targets a protein called CD79b that's found only on B cells, a white blood cell that's the starting point for diffuse large B-cell lymphoma. When Polivy binds to B cells, the chemotherapy "payload" is released, triggering cell death.
In clinical testing, Roche paired Polivy with its blockbuster cancer drug Rituxan (rituximab) as well as the older chemo drug bendamustine. Results showed the combination spurred complete responses in 16 of 40 patients, compared to only seven of the 40 study participants treated with Rituxan and bendamustine alone.
The Phase 1b/2 study looked first at complete response rates, but an exploratory analysis conducted by Roche found improved overall survival and progression-free survival among those patients given Polivy.
While addition of Polivy was associated more frequently with low blood cell counts, infection and transfusion rates were similar between the two study arms.
Polivy will cost roughly $90,000, based on the labeled dosing and the average patient weight from the trial supporting approval, Roche said. Patients who receive Polivy will take the drug along with Rituxan and bendamustine for approximately four months.
For most of the 18,000 Americans diagnosed with DLBCL each year, Rituxan and a combination of chemotherapies known as "CHOP" can result in remissions. But between 30% and 40% relapse, resulting in rapidly growing cancers with more limited treatment options.
Recently, CAR-T cancer therapy has emerged as a potentially effective treatment for these relapsed and refractory patients. Gilead's Yescarta (axicabtagene ciloleucel), for example, holds a similar approval to what the FDA granted Polivy, although it covers several other variations of large B-cell lymphoma. Other CAR-T treatments are being studied in previously treated DLBCL as well.
Roche, however, sees Polivy being used differently.
"Polatuzumab will be a drug that can be given right away," said Michael Wenger, a senior group medical director at Roche, in an interview last December. "Typically patients with relapsed DLBCL have a very aggressive course of disease, so they need treatment very soon."
CAR-T, by contrast, requires significant processing time as patient immune cells are genetically engineered to seek out cancer.
Physicians and specialists surveyed by Cowen in March indicated they viewed Polivy as best used before CAR-T therapy as a transitional treatment, or in patients for whom CAR-T failed.
Other companies are aiming for the same market. MorphoSys plans to file before the end of the year for U.S. approval of its drug tafasitamab in relapsed or refractory DLBCL. Recently announced results from a single-arm Phase 2 study showed 34 of 80 patients experienced a complete response to treatment.
For Roche, Polivy's approval is just a first step. The pharma is testing the drug in combination with Rituxan and chemotherapy in previously untreated DLBCL patients.
And in non-Hodgkin lymphoma more broadly, Roche has developed two bispecific therapies aimed at CD20 and CD3 that it believes offer a better profile than CAR-T therapy. Both are in Phase 1 testing.
Securing cancer drug approvals is made more important, too, by expiring market exclusivity for Roche's top-sellers Rituxan, Avastin (bevacizumab) and Herceptin (trastuzumab).