Going Virtual: GSK’s Multiple Myeloma Drug Belantamab Tapped For US FDA Online AdComm In July
Executive Summary
Announcement of the 14 July Oncologic Drugs Advisory Committee meeting follows a successful, two-day trial run of the virtual format by the oncology pediatric subcommittee that featured a mix of prerecorded and live sponsor presentations and strict adherence to a call/response approach to ensure orderly conduct.
Having successfully navigated a two-day, virtual advisory committee review of cancer drug pediatric development plans, the US Food and Drug Administration is ready to embark on its first application-specific virtual meeting, with the oncology panel once again serving as a test bed.
On 14 July, the Oncologic Drugs Advisory Committee will meet via an online teleconferencing platform to discuss GlaxoSmithKline PLC’s belantamab mafodotin, the agency announced in a Federal Register notice.
The anti-B-cell maturation antigen therapy is undergoing priority review for treatment of adults with relapsed/refractory multiple myeloma who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent. The biologics license application user fee date is in August. (Also see "GSK Files Its BCMA Drug In Multiple Myeloma" - Scrip, 17 Dec, 2019.)
It appears the first virtual, application-specific AdComm will involve a drug that holds breakthrough therapy designation, a big pharma sponsor with extensive AdComm experience, an oncology review division that prides itself on efficiency, and an advisory committee whose pediatric experts already have successfully tested the waters of an online platform.
Given the COVID-19 pandemic and related travel and social distancing restrictions, the Center for Drug Evaluation and Research has been preparing for the potential of virtual AdComms for applications with near-term user fee goal dates. (Also see "Virtual Advisory Committees Are Coming: US FDA Panels Will Be Smaller, More Focused" - Pink Sheet, 15 Apr, 2020.)
It now appears the first all-virtual, product-specific AdComm will involve a product that holds breakthrough therapy designation, a big pharma sponsor with extensive AdComm experience, an oncology review division that prides itself on efficiency, and an advisory committee whose pediatric experts already have successfully tested the waters of a virtual platform.
Pediatric Plan Reviews Are Solid Test Run
The FDA said it is continuing to evaluate different format scenarios for virtual meetings. However, given the relatively positive experience of the ODAC pediatric subcommittee’s recent review of pediatric development plans for four investigational cancer drugs, the agency may well choose to take a similar approach with the belantamab meeting. (Also see "US FDA Oncology AdComm's Pediatric Study Reviews Go Virtual" - Pink Sheet, 3 Jun, 2020.)
The 17-18 June meeting served as a solid test run for an application-specific review, with a mix of live and prerecorded sponsor presentations and strict instructions for panelist conduct during the question-and-answer and discussion portions of the meeting.
Despite a large panel that reached 19 committee members at times, the clarifying questions and discussion sections of the meeting were orderly, and subcommittee chairman Alberto Pappo, a pediatric oncologist at St. Jude Children’s Research Hospital, was a stickler for enforcing the rules of the road in the virtual environment.
Although there were technological bumps along the way, none inflicted any major damage on the proceedings.
Nevertheless, the virtual format benefitted from the fact that these were relatively noncontroversial discussions, with no voting questions for the panel and only four open public hearing speakers. Viewing also was aided by posting of the sponsors’ presentations on the agency’s website just prior to each day’s session.
Choice Of Presentation Formats
As with a Center for Biologics Evaluation and Research virtual AdComm in May, the pediatric oncology subcommittee meeting was conducted over the Adobe Connect platform. (Also see "Virtual Advisory Committees Pose Technical And Practical Challenges For US FDA, Sponsors" - Pink Sheet, 18 May, 2020.)
In his opening remarks, Pappo announced the meeting would operate under a “call/response method” whereby he would call each panelist’s name to prompt them to speak. During introductions of advisory committee members and FDA personnel – all of whom would normally be seated at a U-shaped table in a large conference room – each individual’s picture appeared on the screen.
Meeting roster for the 17-18 June virtual AdComm
Source: FDA
The FDA said sponsors were given the option of making prerecorded or live presentations. (See sidebar below.)
The first sponsor on the agenda, Salarius Pharmaceuticals, was the only one of the four companies to go the prerecorded route – a fact that quickly became obvious when Pappo invited the company to begin its presentation but nothing happened.
After 82 seconds of dead air, Pappo asked, “Are we able to start the presentation?” After 19 more seconds of silence, an FDA staffer said, “We are working on it.”
David Arthur, CEO of Salarius, then chimed in to say the company prerecorded its presentation and submitted it to the agency. “I believe we’re looking for the committee to begin the recording.”
“Yes sir, that is correct,” the FDA staffer said. “We’re working on bringing that up.”
After another 90 seconds of dead air, the company’s presentation began playing. At the conclusion of the recorded presentation, which featured a total of four speakers, Salarius representatives were available to field committee members’ questions in real time.
Raise Your Virtual Hand
Pappo laid out the rules of the road for the clarifying questions period.
“Please use the raise hand icon to indicate that you have a question,” Pappo told panelists. “Please remember to put your hand down after you have asked your question, and please remember to state your name for the record before you speak. It would be helpful to acknowledge the end of your question with a ‘thank you’ and end of your follow-up question with a ‘that is all for my questions’ so we can move on” to the next panelist.
Pappo repeated this instruction after each of the subsequent sponsor presentations. The virtual hand-raising approach also was used during the discussion periods. It generally working well in promoting orderly and efficient Q&A and discussion, except for when panelists mistakenly kept their virtual hand raised after their questions had been asked and answered or their comments completed.
Celgene Encounters Problems With Slides
The remaining three sponsors – Celgene Corp. (Bristol-Myers Squibb Co.), Tessa Therapeutics Pte. Ltd. and Syndax Pharmaceuticals Inc. – opted to give their presentations live. Celgene quickly ran into problems.
“Before I get started, I just want to ask if anyone can see the slides?” said Sherry Leonard, director of global regulatory strategy at Celgene.
“We can see the slides,” Pappo responded.
“I cannot see the slides,” said Gregory Reaman, associate director for pediatric oncology in the FDA’s Oncology Center of Excellence.
“I cannot see the slides as well, so I wanted to make sure before I start that they are visible to most people,” Leonard said.
“All I see is a green circle twirling around,” Reaman said.
FDA staff announced there would be a five-minute break to figure out the connection issues. When the meeting resumed, agency staff told participants that in order to see the slides they should disconnect from their VPN, which can use a lot of bandwidth and cause delays.
However, Celgene still was not in the clear, yet. During a presentation by Mark Kieran, senior director of pediatric oncology at Bristol-Myers Squibb, multi-colored bar graphs in two slides on adverse events with marizomib monotherapy and combination therapy failed to appear on the screen.
“Both of them are missing the material,” Kieran said. “I could kind of point it with my hand if we were sitting in front of each other, but unfortunately without the images here it’s going to be hard to show people the results.”
There also were the usual technical snafus common in the virtual setting, including audio fading in and out, random background noises, and the ubiquitous “can you hear me now” query. (Also see "‘Can You Hear Me?’ US FDA Begins Meeting Virtually" - Pink Sheet, 18 May, 2020.)
It also would seem that some of the FDA’s boilerplate language developed for live advisory committee meetings may need tweaking in the virtual setting.
For example, the admonition that panelists should not discuss the meeting topics at lunch amongst themselves or with members of the audience may be less meaningful now that AdComm members are not lunching with public observers in the hallways of the FDA’s White Oak headquarters.
The FDA’s Reaman thanked the panelists “for your flexibility and patience again with doing this pediatric subcommittee meeting in a virtual setting. Hopefully this won’t be the everlasting normal, but then again maybe it will.”
At the end of the second day, the consensus seemed to be that things overall had gone well.
In his closing remarks, Reaman thanked the panelists “for your flexibility and patience again with doing this pediatric subcommittee meeting in a virtual setting.”
“Hopefully this won’t be the everlasting normal, but then again maybe it will,” he said. “But I think despite all the difficulties that we envisioned, I think things actually went pretty smoothly from a technological perspective.”
“It went very, very smoothly,” Pappo said.