I had high expectations when I saw the list of speakers for an FDA Cell & Gene Therapy Roundtable held today. Admittedly, earlier when I had seen the meeting announced and no speakers were listed, I wondered how it might go.
Would it be like the earlier RFK Jr. regenerative medicine roundtable? That private meeting just added to concerns that the FDA under Kennedy might advocate for less oversight of unproven cell therapy and regenerative clinics. Or he might reduce FDA oversight of cell therapies in harmful ways.
FDA Cell & Gene Therapy Roundtable
Put together by the FDA’s CBER branch under new director Vinay Prasad, today’s public meeting was very different. It was heavy on strong science. Still, I have some concerns about how it played out.
Below are some streams of thought as I was watching the roundtable so this post is somewhat rougher than usual.
Where I have included things in quotes, they are not necessarily meant to convey the precise statements but give the sense of what speakers emphasized in key statements. I was just taking notes on the fly while watching and doing other work.
Marty Makary opening comments
FDA Commissioner Marty Makary started things off. He called Prasad a medical genius a few times.
Said we (meaning FDA) believe in right-to-try or RTT. Other speakers later also mentioned RTT.
“We want to look at things as patients or parent of a child would.” That’s important, but the FDA needs to have its own, different vision too.
Vinay Prasad opening comments
Prasad said, “We will emphasize science and common sense”, similar to what Makary said.
He emphasized transparency at the FDA.
A bold statement followed: “We will make therapies available at the first sign of success.” I found this concerning even though he said FDA will follow up.
Is this a sign that the FDA’s oversight of cell and gene therapies could become more like the Japanese conditional regenerative medicine approval system, which has had many problems?
“We will focus on both trials and real-world evidence.”
They will do a listening tour with CEOs, which is interesting.
Okay, on to the invited speakers.
FDA Cell & Gene Therapy Roundtable panel speakers
Terrence Flotte
He’s the leader of ASGCT.
Flotte emphasized better access.
There was discussion of the risks of market therapy failure making therapies unavailable even if the science is solid. This was a theme at the meeting.
David Liu
He mentioned base and prime editing. Emphasized rare diseases.
Goal: on-demand CRISPR or other genetic treatments, making them routine, standard of care
Liu noted the remarkable case of Baby KJ who received a bespoke CRISPR therapy that so far has been very helpful.
He believes we can aim to treat 1,000 patients by 2030 with personalized genetic treatments.
Catherine Bollard
She went over some gene therapy history.
What about CAR-T in pediatric cases? Less progress there, which I hadn’t realized so clearly before.
Crystal Mackall
She discussed pediatric gene therapies for cancer.
One example was cell therapy for diffuse midline glioma, tumors that are a major focus of my lab.
Like others, she noted that scientific success hasn’t been matched in the clinic.
Carl June
He articulated his concerns about risks to US leadership in this field. “Over-cautious regulation can stifle progress.”
Bold statement: “FDA does not need to regulate autologous gene-modified cell therapies.” He said that they can be regulated locally via IRBs instead. The FDA can come in later when larger trials may begin, he added. One thought here from me: not all IRBs do a great job so this seems very risky to me.
“Discoveries in our labs are often taken to clinical studies in China or elsewhere.” This was a recurring theme in the meeting and something I had not fully realized before the meeting.
Don Kohn
He emphasized gene therapy, giving the example of his team’s game-changing treatment of dozens of pediatric patients with SCID. Commercialization of this technology has had challenges due to the initial biotech stepping aside and handing it back to UCLA.
Kohn noted that CIRM support here has been crucial, but more funding is needed in the long run from other sources.
Three suggestions: A shift to “GMP-lite” would reduce costs; we need to reduce the burden of transitioning to commercialization; and there could be an accelerated pathway for BLA approval.
Jayme Locke
Transplant surgeon.
Emphasized RTT.
Mentioned President Trump several times.
Terry Pirovolakis
He’s a CEO & Founder of Elpida Therapeutics and a parent of a child with a rare disease. He started a biotech and has worked toward new therapy development. This was a compelling personal story applied to the broader field.
Paula Cannon
Past President of ASGCT.
Envisions “plug-and-play” approaches. Looking for a way to “put the foot on the gas pedal.”
Tim Hunt
CEO of ARM. Companies were frustrated with the FDA in the past and ended up going to other countries. “Nicole Verdun came in to OTP and made a difference.”
“Time is life” for these ultra-rare conditions, which is a good point also raised by others.
Charlie Gersbach
Gene editing researcher.
Mentioned in vivo cell editing as a therapy.
A note here. These summaries are in the order of the talks. I listened to all the talks but didn’t have time to take notes on all of them. To this point in the meeting, speakers have not mentioned stem cells much, which is surprising. There has been far more emphasis on gene therapies than cell therapies even beyond stem cells.
Fyodor Urnov
He also talked about Baby KJ’s story.
“We want to shorten the time and cost for CRISPR use.”
“We have to protect young researchers” — reading between the lines this could be a comment about risks to young scientists today from hits to the NIH, etc.
Sean Morrison
“Here as a representative of ISSCR”. He noted the goal of development of non-animal models of disease.
Importantly, he brought up the reality of the “bad actors” in this space attempting to sell snake oil. He’s talking mainly about unproven stem cell clinics.
This has not been addressed by others at the meeting. There are around 2,000 companies like this in the U.S.
“There’s no rationale for how umbilical cord cells could treat ALS, etc.” These companies ignore GMP practices.
The concern is that lowered FDA regulations could enable these firms.
Thanks to Sean Morrison, who provided needed balance. I would note that there are now clinics selling unproven oligonucleotide therapies in the U.S. too.
Comments from administration leaders: RFK Jr., et al.
These leaders highlighted individual cases that are interesting. My thought: do these single cases translate to large, more heterogeneous populations? There are reasons to think they may not.
Oz vaguely mentioned benefits of stem cell treatments. Some years back on his talk show they discussed the risks of unproven stem cells.
Then came Kennedy. He emphasized how poorly America is doing health-wise. He also noted progress toward making an approved cell and gene therapy for sickle cell available across the country. They are talking to insurance companies about this.
Another notable statement: “give us a list of regulations to get rid of.”
Kennedy did not mention stem cells, but there is breaking news on him having gotten unproven stem cells outside the U.S. Stay tuned for more on this.
Overall thoughts on the roundtable
This was a top-notch meeting with great speakers and leaders in the field.
My main overall concern was the major emphasis on promoting more speed and access. These could be positive goals, for sure. However, accumulating needed data can take time and care.
There may be creative ways to further accelerate the product evaluation process, yet few speakers emphasized the need for rigorous data to balance that.
Why is this important? Strong data protects patients and clinical trial participant safety. This also protects the field from setbacks like have happened to the gene therapy arena in the past.
Realistically, not everything can be done in a “plug-and-play” rapid-fire kind of way.
Several speakers also hit requirements for placebo-controlled trials.
Some noted “parachute trials” as a way to suggest trials (or at least rigorous trials) are not really needed in some cases. In other words, they are saying: it’s self-evident that parachutes save lives so we shouldn’t have to do trials on them and the same is true for some cell and gene therapies. I would counter that very little is self-evident about investigational cell and gene therapies. They are infinitely more complicated than parachutes.
So there wasn’t much balance to the meeting.
We need to take patient views very seriously. The FDA needs more efficient processes. Some things logically require relatively less oversight, but it would be easy for the FDA and CBER to now swing too wildly toward less oversight. We also have to acknowledge bad actors. There are thousands of them.
Other impressions —
Many people mentioned concerns about China taking leadership in this space.
Several speakers mentioned Nicole Verdun as being a key FDA figure in the efficient therapy development. She is one of the few CBER leaders to survive the transition to this administration and the speakers today maybe hinted why.
The elephant in the room: devastating NIH cuts
Almost every therapy mentioned at this meeting was made possible by NIH-funded research.
The elephant in the room today was the devastating impact of NIH funding cuts the last four months. These cuts, unless reversed, are going to slow research on cell and gene therapies in ways that cost lives. It can’t be ignored.