FDA Clock Starts for AstraZeneca and Merck in Prostate Cancer, Roche in DLBCL

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Tuesday morning saw the FDA acceptance of a supplemental New Drug Application (sNDA) and supplemental Biologics License Application (sBLA) for three industry powerhouses. 

The FDA has accepted the sNDA for AstraZeneca and Merck's Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone for metastatic castration-resistant prostate cancer (mCRPC).

Developed and commercialized jointly by the industry giants, Lynparza was first approved in late 2014 for advanced ovarian cancer. Since then, the drug has continued to win regulatory nods for oncology indications including BRCA-mutated breast cancer, HER2-negative high-risk breast cancer and pancreatic cancer.

The regulator has set an action date for the fourth quarter of this year, in accordance with the Prescription Drug User Fee Act.

Of all prostate cancer patients in the United States, 10 to 20% eventually progress to a castration-resistant disease within five years. Moreover, by the time castration-resistant prostate cancer (CRPC) is diagnosed, some 80% of patients may have already developed tumor metastasis. At this stage, patients suffer from poor disease prognosis, grim survival outlook and limited treatment choices.

“Today’s news is another step towards bringing forward a new, much-needed treatment option in this setting. If approved, Lynparza with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease," Susan Galbraith, executive vice president, oncology R&D at AstraZeneca said in a statement.

In May 2020, Lynparza received the FDA's greenlight for mCRPC patients harboring mutations in the homologous recombination repair gene. This latest sNDA filing offers the combination of olaparib with abiraterone and prednisone or prednisolone as an even more effective way of improving outcomes in this patient population.

The sNDA uses data from the Phase III PROpel trial, which showed that the complete drug combo cut the risk of mCRPC progression or death by 34%, as opposed to the same regimen without Lynparza. This effect, which was statistically significant, did not come with unexpected side effects.

Genentech Wins DLBCL sBLA for Polivy Combo

Just ahead of AstraZeneca and Merck is Genentech, a Roche subsidiary. On Monday, the company announced that the FDA has accepted its sBLA for Polivy (polatuzumab vedotin-piiq) in combination with Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) for diffuse large B-cell lymphoma (DLBCL).

Genentech’s sBLA drew primarily from the pivotal Phase III POLARIX trial, which showed that adding Polivy to R-CHP cut the risk of disease progression, relapse or death by nearly 30% relative to standard of care. POLARIX was also the first study in 20 years to demonstrate a clinically meaningful increase in progression-free survival in DLBCL patients, as compared with standard of care.

“The POLARIX study results suggest that Polivy plus R-CHP could transform the treatment of this aggressive malignancy, and we are working with the FDA to bring this combination to newly diagnosed DLBCL patients as soon as possible,” Levi Garraway, M.D., Ph.D., chief medical officer and head of global product development at Genentech said. “We hope it will become the new standard of care for the first-line treatment of DLBCL, potentially reducing the need for subsequent treatments and limiting patient burden.”

DLBCL is an aggressive blood cancer that is prone to disease relapse. While the disease initially responds to standard of care - which consists of Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone - it eventually returns in some 25% of patients. In most cases, relapses occur within two years, and those who end up needing more lines of treatment often see worse outcomes.

The FDA stated it will review the drug and make a decision by April 2023.