Rhythm Pharmaceuticals (RYTM) Q4 FY25 earnings call: guidance and Q&A

Are there any changes to enrollment criteria or other features for Bivamelagon Phase 3, given FDA feedback?

The trial will largely mimic the setmelanotide Phase 3 in sample size and duration. Potential modifications to patient-reported outcome measures are being considered, but no specific FDA feedback was given on this.

“I think to your point, the trial will largely mimic our Phase 3. We continue to look at our patient reported outcome measures. Are there other things we can do to get better and better at, for example, understanding hyperphagia/hunger.”

asked by Derek Archila · answered by David Meeker

How might guidelines evolve for early intervention in post-surgical HO patients?

While the trial had a 6-month post-surgery entry criterion for stability, in the real world, earlier intervention is preferred once HO is diagnosed, similar to thyroid hormone replacement. No specific guidance in the label is expected to mandate waiting.

“In the real world, which is your question, and we've had this feedback from multiple thought leaders and the like, I mean, earlier is better. Why would you know the patient has HO, why would you make them wait 6 months to begin intervene? You wouldn't do that for their thyroid hormone replacement, for example.”

asked by Derek Archila · answered by David Meeker

What is the next data update for the PWS study, and what type of deepening response is expected?

The next update for the 17 patients remaining on drug is still on track for midyear. The goal remains to clear 5% on the BMI change, and hunger scores (HQ-CT) will be collected, acknowledging the uncontrolled nature of the trial.

“I think our goal remains the same. We'd be looking to clear 5% on the BMI change. We'll see how we do there. And of course, we'll collect hunger. I mean, the hyperphagia scores, HQ-CT, we shared that data in December with the caveat. This is an uncontrolled trial.”

asked by Tazeen Ahmad · answered by David Meeker

What is the basis for the higher probability of success in POMC/PCSK1 and SH2B1 substudies?

The higher probability for POMC/LEPR is based on the ability to identify pathogenic variants and full enrollment. LEPR was under-enrolled. SRC1 has many variants of unknown significance. SH2B1 has hope due to deletions, but also includes missense mutations with unknown significance.

“So the way we've handicapped this is, yes, we think that the POMC/LEPR are the most likely to be positive, and that's based on the fact that we did have an assay going into the trial that allowed us to determine which of the variants were most likely to be pathogenic meaning that they had true loss of function.”

asked by Whitney Ijem · answered by David Meeker

How does the FDA's 12-month Phase 3 requirement for Bivamelagon impact 718 development, and what about quality control for ex-US enrollment?

718 will likely face similar 12-month Phase 3 requirements, though management would seek further FDA discussion. Quality control for ex-US trials is not a concern due to the sophistication of global CROs and careful site selection, despite the challenge of finding rare disease patients.

“So first on 718, yes, the read-through there would highly likely to be the same. I mean, to be honest, we'd go back, I would look to have another conversation with them. I think part of Biva is it's a small molecule. I think 718 is a peptide. It's highly analogous to setmelanotide.”

asked by Corinne Jenkins · answered by David Meeker

What will be the dosing paradigm for Bivamelagon Phase 3, and is there an update on identified HO patient numbers?

The target dose for Bivamelagon Phase 3 will be 600mg, with dose escalation from 200mg, as 600mg shows continued dose response. The number of identified HO patients has increased beyond the previously cited 2,000, reflecting ongoing identification efforts and a growing opportunity.

“So, what was the question on? Yes, the dosing. So we will dose escalate from 200 up to 600, 600 will be the target dose. We look at the data the same way you did. I think there is a difference between 400 and 600 milligrams.”

asked by Philip Nadeau · answered by David Meeker

How will the launch cadence for acquired HO compare to BBS, considering regulatory interactions and payer coverage?

Similarities include the need for diagnosis education and payer policy updates (expected 3-9 months post-approval). Differences include stronger data for targeting physicians and medical centers for aHO, allowing for earlier identification of incident patients, which gives more confidence in the launch.

“I think from a similarity perspective, there's still a lot of opportunity, as we've outlined, just in terms of getting these patients to an actual diagnosis of acquired hypothalamic obesity versus just being seen as a patient with obesity for many causes that may not be the root cause in terms of what they are going through.”

asked by Samantha Semenkow · answered by Jennifer Chien

Can you expand on Bivamelagon dose selection, and is maintenance dosing possible if patients reach normal BMI?

The target dose will be 600mg, with 200mg likely being subtherapeutic. Due to the hormonal deficiency pathophysiology, patients are expected to maintain their target dose rather than dose down for maintenance, as observed with setmelanotide.

“I do think 200 is probably on the border in terms of being therapeutic for most patients. I think 400 to 600 is more likely in range and 600 does seem to have a continued dose response. And so 600 for sure will be our targeted dose just the way 3 milligrams was our targeted dose in the HO setmelanotide trial.”

asked by Lisa Walter · answered by David Meeker