In a step toward what may become the new normal, at least for now, the Pediatric Oncology Subcommittee of the FDA’s Oncologic Drugs Advisory Committee is meeting virtually Wednesday and Thursday to review pediatric development plans for four cancer drugs.
Wednesday, the subcommittee considered the development plans for Salarius Pharmaceuticals Inc.’s SP-2577 (seclidemstat mesylate) as a treatment of Ewing sarcoma and advanced solid tumors in the pediatric population and Bristol Myers Squibb Co.’s marizomib to treat diffuse intrinsic pontine glioma, a type of brain tumor. Thursday, the panel will advise on pediatric development plans for Tessa Therapeutics Ltd.’s CD30.CAR-T to treat relapsed and refractory CD30-positive classical Hodgkin lymphoma and Syndax Pharmaceuticals Inc.’s SNDX-5613, being developed to treat relapsed or refractory leukemias.
It’s the first adcom meeting to consider product development since the agency began canceling or postponing meetings and events March 10 in response to the spread of COVID-19. As a result of that decision, six adcoms were postponed indefinitely, three were canceled and no new meetings have been added to the agency’s adcom calendar. (See FDA adcoms impacted by COVID-19, below.)
Some of the impacted meetings were scheduled to bring committee members up to date on FDA research programs or to get input on general issues involving device classifications or antiseptics for food handlers.
Others were called as part of the agency’s review of specific drug and device applications. Delays of those meetings increase the potential of missed approval/clearance dates. As Difei Yang, managing director at Mizuho Securities USA LLC, noted, the postponements raise more concerns than the canceled meetings.
At least one of the cancelations was not a result of the pandemic. In scrubbing the April 23 Medical Imaging Drugs Adcom for Tauvid (flortaucipir F18), a radioactive diagnostic agent sponsored by Eli Lilly and Co. subsidiary Avid Radiopharmaceuticals Inc., the FDA said it had resolved the scientific issues it had wanted to discuss with the panelists. Tauvid was approved May 28.
The other canceled meeting focusing on a specific product involved DBV Technologies SA’s peanut allergen extract that’s being developed to treat children, age 4 through 11, who have a confirmed peanut allergy. The FDA said it canceled the May 15 meeting to allow more time for it to “review outstanding issues.” It added that it would continue to evaluate the product and, if needed, reschedule an adcom later.
In a question-and-answer guidance released last month, the FDA warned that it might not be able to sustain its performance level in meeting all its goal dates, as it was having to shift its limited resources to meet the increasing demands of development of COVID-19 diagnostics, therapies and vaccines.
The guidance addressed adcoms only briefly, saying that the agency was continuing to evaluate the feasibility of conducting the meetings virtually. “The review divisions will work closely with sponsors and applicants for specific applications that could potentially be affected and will discuss options for pursuing virtual meetings,” according to the guidance.
When it comes to the adcoms that have been postponed, “the outlook … is muddied,” Yang said. For instance, the April 21 meeting in which the Pulmonary-Allergy Drugs Advisory Committee was supposed to weigh in on a supplemental asthma application for Glaxosmithkline plc’s Trelegy (fluticasone furoate/umeclidinium/vilanterol) has not been rescheduled, even though it has a June 30 PDUFA date.
Another product caught in the pandemic delay is Intercept Pharmaceuticals Inc.’s obeticholic acid, being developed as a breakthrough therapy with priority review to treat liver fibrosis due to nonalcoholic steatohepatitis. Although not on the FDA’s calendar, an adcom for the drug was tentatively scheduled in April and then tentatively moved to June 9.
A few weeks ago, Intercept announced that the FDA had unexpectedly postponed the meeting once again to give it time to review additional data it had requested. The agency said it would contact the company in the near future with a new proposed adcom date. Given the postponement, Intercept said the FDA’s review of the new drug application likely would extend beyond the June 26 PDUFA date.
While the FDA holds adcoms for opioid applications and the first biosimilar to target a biologic, it typically convenes an adcom for other drugs and devices only when it needs the scientific and clinical expertise of the committee members in weighing the risk-safety profile of a product or to answer unresolved questions about the interpretation of data, trial conduct, safety signals, etc. While sponsors may anticipate an adcom, they don’t know if one will be required until informed of it by the FDA.
Going forward, Yang said two adcom meetings are expected ahead of September 2020 PDUFA dates – for Mallinckrodt plc’s terlipressin, being evaluated as a treatment of hepatorenal syndrome type 1, and Mesoblast Ltd.’s Ryoncil (remestemcel-L), an allogeneic cell therapy for children with steroid-refractory acute graft-vs.-host disease.
As of last week, neither company had been notified of an adcom date, Yang said.
Last year, the FDA conducted 17 adcoms between March 10 and June 30. In 2020, with this week’s meeting of the Pediatric Oncology Subcommittee, the agency will have conducted two adcoms, both virtual, within the same timeframe. (The other meeting involved bringing the Cellular, Tissue and Gene Therapies Advisory Committee up to date on research being conducted at the Center for Biologics Evaluation and Research.)
Also last year, the FDA held more than 20 adcoms from July through December. Currently, this week’s adcom is the last one listed on the 2020 calendar.