Dianthus Therapeutics (NASDAQ:DNTH) said it has made an “early go” decision to continue its CAPTIVATE Phase 3 trial evaluating claseprubart in chronic inflammatory demyelinating polyneuropathy (CIDP), based on a planned interim responder analysis from Part A of the ongoing pivotal study. Management said the company is not disclosing specific responder rates or other detailed efficacy data at this time in order to protect the integrity of the registrational trial.
CAPTIVATE trial design and interim “go” criteria
CAPTIVATE is a single, two-part Phase 3 trial intended to support a biologics license application (BLA) in adults with CIDP. Part A is an open-label period in which patients who are standard-of-care naive, stable, or refractory receive (or are switched within seven days to) claseprubart 300 mg delivered as a 2 mL subcutaneous injection every two weeks for up to 13 weeks. To advance to Part B, patients must improve by at least one point on the NCAT score at two consecutive visits, starting at week 5.
The company said it targeted an interim confirmed responder rate in the 40% to 50% range among the first 40 patients completing Part A, a benchmark management linked to prior open-label CIDP data for riliprubart (another C1s inhibitor). Randhawa said Dianthus reached the upper end of that target—20 NCAT responders—before 40 patients completed Part A.
Safety commentary from interim analysis
On safety, Randhawa said the company remains reassured by claseprubart’s profile in CIDP, reporting no concerning safety events, including no clinical symptoms of autoimmune activation, concerning bacterial infections, or discontinuations due to safety or tolerability. In the Q&A, Randhawa further stated there were “0 indications” suggestive of autoimmune activation, including drug-induced lupus.
Study design changes: dropping 600 mg and reducing enrollment
Based on the interim analysis, Dianthus is implementing several changes to CAPTIVATE:
- Part A remains unchanged (claseprubart 300 mg subcutaneous every two weeks).
- The 600 mg arm will be removed from Part B, and Part B will now be a two-arm blinded randomized withdrawal study comparing 300 mg every two weeks versus placebo.
- The Part A responder target is being raised from 40% to 50%, which management characterized as a “comfortable bar to meet.”
The company said these changes reduce the projected number of patients needed in Part B from 192 to 128, and reduce the number of patients dosed in Part A from 480 to 256. Randhawa said eliminating the 600 mg arm avoids splitting alpha across dose groups and, as described on the call, results in “stronger power to show a separation.”
Chief Executive Officer Marino Garcia framed the decision as a “double upside scenario,” saying the company not only hit its responder target earlier than expected but also raised its Part A responder assumption to 50%, which he described as a signal of confidence in the data observed so far.
Management’s positioning versus prior CIDP studies
Garcia highlighted differences between CAPTIVATE and the ADHERE CIDP study of efgartigimod, including that CAPTIVATE allows refractory patients and does not require patients to wash out and relapse before entering Part A. He also noted that CAPTIVATE’s Part A responder definition is based on improvement above baseline after switching from prior therapy, whereas he said ADHERE’s response rate reflected recovery after a required relapse.
Management repeatedly cautioned against cross-trial comparisons, with Randhawa noting the interim analysis includes a relatively small number of patients. Still, executives suggested the response observed to date exceeded internal expectations based on precedent data. In Q&A, Randhawa said the company needed to see a “substantially higher” response rate than the 40%–55% range to justify raising the responder target to 50%.
Market opportunity, pipeline milestones, and cash runway
Garcia described CIDP as a “multi-billion” market and cited an estimate of 40,000 patients in the U.S. He also summarized feedback from a company-sponsored survey of 80 U.S. neurologists treating CIDP, which indicated interest in therapies offering greater efficacy and sustained symptom control, improved tolerability without boxed warnings or REMS, and more convenient administration, ideally self-administered.
Looking ahead, management said it expects to provide guidance later this year on when to anticipate CIDP top-line results. The company also outlined additional milestones:
- Generalized myasthenia gravis (gMG): plans to initiate a Phase 3 trial in mid-2026 evaluating 300 mg every two weeks and 300 mg once monthly versus placebo, with top-line results expected in the second half of 2028.
- MMN: top-line Phase 2 data from the MoMeNtum trial expected in the second half of this year; executives said they intend to keep both 300 mg and 600 mg arms in MMN given limited data in the indication and because the study is already well advanced.
- DNTH212: planned disclosure of prioritized indications in the first half of this year and top-line results from a Phase 1 healthy volunteer study in the second half of this year; management said it expects to prioritize three indications from a shortlist of six previously discussed.
Ryan Savitz, the company’s chief financial and business officer, was introduced on the call, and management reiterated a cash balance of approximately $514 million as of Dec. 31, which the company said is expected to fund operations into 2028.
About Dianthus Therapeutics (NASDAQ:DNTH)
Dianthus Therapeutics, Inc, a clinical-stage biotechnology company, develops complement therapeutics for patients with severe autoimmune and inflammatory diseases. It is developing DNTH103, a monoclonal antibody, which is in Phase 2 clinical trial, for the treatment of generalized myasthenia gravis, multifocal motor neuropathy, and chronic inflammatory demyelinating polyneuropathy. Dianthus Therapeutics, Inc was founded in 2019 and is headquartered in New York, New York.
