391: Breaching the IBD efficacy ceiling, and sham surgeries
Episode
29 min
Read time
2 min
Topics
Fundraising & VC, Leadership, Design & UX
AI-Generated Summary
Key Takeaways
- ✓IBD Efficacy Ceiling: Every approved IBD drug class — including biologics like Entyvio and Skyrizi — achieves clinical remission in only roughly 25–30% of patients. Combination therapies targeting multiple disease pathways simultaneously show additive efficacy without apparent additive safety risks, making them the most viable strategy to push remission rates meaningfully above that ceiling.
- ✓Combination Therapy Benchmarking: Johnson & Johnson's VEGA trial established the first randomized proof that combining two biologics yields additive IBD remission rates, reaching just under 50%. Spire's hypothesis is that replacing weaker components — specifically TNF inhibitors — with superior mechanisms like alpha-4-beta-7 or TL1A could add 10 or more percentage points on top of that benchmark.
- ✓TL1A as a Pipeline-in-a-Product Target: TL1A inhibitors are being evaluated across up to seven distinct indications in 2025, including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, and MASH. This broad applicability — comparable to Humira's multi-indication profile — explains why Blackstone committed $400 million to back a single TL1A program developed by Teva and Sanofi.
- ✓Combination Pricing Strategy: Payers currently reject off-label dual-biologic combinations because they require covering two branded drugs at double the cost with no combined clinical data. Spire's approach — co-formulating two antibodies into one branded product dosed four times annually — is designed to be priced comparably to a single biologic, making payer approval and cost-effectiveness arguments substantially more straightforward.
- ✓FDA Regulatory Whipsaw in Rare Disease: The shift from Peter Marks to Vinay Prasad at FDA's cell and gene therapy division represents a move from permissive, flexible approval standards to a significantly higher evidentiary bar. Rare disease developers should anticipate stricter controlled trial requirements — including controversial sham surgery controls — rather than relying on historical comparator data for approval.
What It Covers
The Readout Loud covers two major biotech stories: UniCure's regulatory standoff with the FDA over sham surgery requirements for its Huntington's disease gene therapy, and Spire Therapeutics CEO Cameron Turtle explaining how combination biologics aim to break IBD's 30% remission ceiling.
Key Questions Answered
- •IBD Efficacy Ceiling: Every approved IBD drug class — including biologics like Entyvio and Skyrizi — achieves clinical remission in only roughly 25–30% of patients. Combination therapies targeting multiple disease pathways simultaneously show additive efficacy without apparent additive safety risks, making them the most viable strategy to push remission rates meaningfully above that ceiling.
- •Combination Therapy Benchmarking: Johnson & Johnson's VEGA trial established the first randomized proof that combining two biologics yields additive IBD remission rates, reaching just under 50%. Spire's hypothesis is that replacing weaker components — specifically TNF inhibitors — with superior mechanisms like alpha-4-beta-7 or TL1A could add 10 or more percentage points on top of that benchmark.
- •TL1A as a Pipeline-in-a-Product Target: TL1A inhibitors are being evaluated across up to seven distinct indications in 2025, including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, and MASH. This broad applicability — comparable to Humira's multi-indication profile — explains why Blackstone committed $400 million to back a single TL1A program developed by Teva and Sanofi.
- •Combination Pricing Strategy: Payers currently reject off-label dual-biologic combinations because they require covering two branded drugs at double the cost with no combined clinical data. Spire's approach — co-formulating two antibodies into one branded product dosed four times annually — is designed to be priced comparably to a single biologic, making payer approval and cost-effectiveness arguments substantially more straightforward.
- •FDA Regulatory Whipsaw in Rare Disease: The shift from Peter Marks to Vinay Prasad at FDA's cell and gene therapy division represents a move from permissive, flexible approval standards to a significantly higher evidentiary bar. Rare disease developers should anticipate stricter controlled trial requirements — including controversial sham surgery controls — rather than relying on historical comparator data for approval.
Notable Moment
In UniCure's original sham surgery control study involving 10 patients, one participant developed a blood clot following the procedure — a serious adverse event that the company now cites as direct evidence that requiring a new sham-controlled Huntington's trial poses genuine, unacceptable patient risk.
Episode Transcript
Welcome to this week's episode of The Read Out Loud, a weekly biotech podcast from STAT. I'm Allison DeAngelis. I'm Anna Feuerstein. And I'm Elaine Chen. It's Thursday, March 4. And on this week's episode, Spire Therapeutics CEO Cameron Turtle joins us to chat about developing new drugs, including combination therapies for inflammatory bowel disease. But first, a recap of the week's news and a word from our sponsor. I'm staff and studio editor Jesse McQuarters, and I'm talking with doctor Fred Applebaum, executive vice president at Fred Hutch Cancer Center. Doctor Applebaum, how has the work done over the past fifty years of Fred Hutch impacted how we treat cancer today? About fifty years ago, Don Thomas and our team showed that marrow transplantation was possible, which enabled us to cure almost every marrow based disease. Today, over one hundred thousand people worldwide undergo a marrow transplant every year. Going forward, we're developing even better immune therapies. Antibody based therapies, cell based therapies that harness the power of the human immune system to eradicate cancer. For more information on Fred Hutch Cancer Center, visit fredhutch.org/lookbeyond. Adam, how was it with both me and Allison gone last week? It was lonely. Like, all I had was Jared to talk to. God. Who wants to talk to Jared for thirty minutes? No. I'm kidding. It it was very nice to have him on, and, as you guys know, Jared and I are friends, so it's pretty easy to just, talk, talk to Jared. But, yeah. I'm glad you guys are back. I hope you guys had a good time off last week. Yeah. I think we both don't wanna be back. Yeah. I'm I Adam, nothing against you, but I'm not sure why I'm working right now. Glad to hear that you're not gonna replace us with Jared anytime soon. No. No. But maybe AI will replace you. I don't know. Or or or replace all of us, I should say. That that could happen fairly soon. That that really could. Well, while we still have jobs, should we talk about biotech news? Let's do it. Okay. Okay. So let's start off by catching up listeners to the disagreement between the FDA and UniCure. As you may remember from previous episodes, UniCure had hoped to submit its gene therapy for Huntington's disease for approval, but regulators turned it down. Now there's contention over whether the company will need to run another trial that includes a control group, a group of people that may need to undergo anesthesia and have a mock surgery. Adam, you've been covering the story. Tell us more. Yeah. It's been kind of all I've done this week. You know, it started on Monday when Unicure, which is the company that's developing this gene therapy for Huntington's disease, issued a regulatory update, which basically kinda, you know, repeated what we had heard late last year was that, you know, there was this fundamental disagreement between the company and …
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“UniCure's regulatory standoff with the FDA over sham surgery requirements for its Huntington's disease gene therapy”
“Spire Therapeutics CEO Cameron Turtle explaining how combination biologics aim to break IBD's 30% remission ceiling.”
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