Skip to content

Inside Health Policy – FDA Grants First 'Breakthrough' Approval Based on 356 Person Study

Inside Health Policy – FDA Grants First 'Breakthrough' Approval Based on 356 Person Study

FDA Friday (Nov. 1) approved a therapeutic combination that more than doubled progression free survival in patients — the first approval under the breakthrough drug designation created more than a year ago with the passage of the FDA Safety and Innovation Act. The agency approved Genentech’s Gazyva for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia (CLL).

The approval was based on a study of 356 participants in a randomized open-label multicenter trial that compared Gazyva used in combination with chlorambucil to chlorambucil used alone. The breakthrough combination treatment “demonstrated a significant improvement in progression free survival: an average of 23 months compared with 11.1 months with chlorambucil alone,” FDA said.

In addition to the breakthrough designation, which means the biologic received attention from FDA’s top officials throughout the development process, Gazyva also received an orphan drug designation and priority review, FDA said.

“Out of the gates it shows how flexible (the breakthrough designation) can be to address very necessary and much-needed treatments for small populations of patients,” said Ryan Hohman, managing director of policy and public affairs at Friends of Cancer Research, which advocated for the creation of the designation.

He said the approval is “very exciting” for the advocacy and cancer community. “The FDA is obviously fully committed to this program,” Hohman said.

As the first approval emerges, stakeholders will be looking for lessons learned to build on existing information about the new program, Hohman said. During the first year of the designation, observers analyzed the products that were receiving designations, but this will likely shift toward the clinical evidence used to gain approvals, especially as FDA approves more breakthrough products, he said.

From the beginning of the program, FDA officials made clear that drug companies using this new pathway would face a high bar and potential challenges in quickly ramping up production, given that clinical timelines would be sped up. FDA included details about the breakthrough program in a guidance document released in June that touched on all of FDA’s expedited programs.

Congress created the designation in FDASIA, which was signed into law last summer. As of Oct. 25, FDA’s drug center received 92 breakthrough requests. The center granted 29 and denied 45, according to FDA statistics.

“Today’s approval represents an important new addition to the treatments for patients with CLL,” said Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s drug center. “This approval reflects the promise of the Breakthrough Therapy Designation program, allowing us to work collaboratively with companies to expedite the development, review and availability of important new drugs.”

FDA approved Gazyva with a black box warning, which means it carries potentially significant risks. The warning pertains to the risk of Hepatitis B reactivation and progressive multifocal leukoencephalopathy — a rare disorder that damages the material covering and protecting nerves in the white matter of the brain, FDA said. The agency noted that these risks are known with other monoclonal antibodies in this class and rare cases were identified during the trial.

The agency’s statistics also show that the center for biologics granted its first designation for a product to move through the new approval process. The biologics center received eight designation requests since the start of the program and is still deciding whether to grant designation status for the remaining seven.