SAN DIEGO, Calif. — October 26, 2026

Ambros Therapeutics, Inc. announced alignment with the U.S. Food and Drug Administration (FDA) on its proposal to introduce an interim analysis using a group sequential design in the ongoing pivotal Phase 3 CRPS-RISE trial evaluating neridronate for complex regional pain syndrome type 1 (CRPS-1). The interim analysis is expected after approximately half of the study participants have completed the trial and could allow the study to stop early if the results warrant it. An independent Data Monitoring Committee will oversee the process under a prespecified statistical analysis plan, which the company intends to align with the FDA. Ambros plans to update the clinical trial protocol and submit a revised statistical analysis plan and committee charter for FDA review. Neridronate has received FDA Breakthrough Therapy, Fast Track and Orphan Drug designations for CRPS. The development programme addresses a significant unmet medical need, as CRPS-1 can cause persistent, severe pain and disability, and there are currently no FDA-approved medicines specifically for the condition.

FDA Alignment Supports Planned Interim Analysis

The proposed group sequential design will allow researchers to assess accumulating trial data before all participants complete the study. The planned interim analysis is expected when approximately 50% of participants have completed the trial, potentially enabling an earlier decision about whether the study should continue. An independent Data Monitoring Committee will oversee the analysis to support appropriate review of emerging data, while a prespecified statistical analysis plan will define the methodology and decision criteria. Ambros intends to revise the CRPS-RISE protocol and submit the relevant documents to the FDA for review. Chief Executive Officer Jay Hagan said the approach could help determine the trial outcome sooner, while Chief Medical Officer Gail Cawkwell noted that the programme builds on earlier studies conducted in Italy and internationally. The proposed interim analysis does not guarantee an early stop or a positive result; the trial’s continuation and conclusions will depend on the prespecified criteria and the data reviewed.

CRPS-RISE Evaluates Neridronate in Patients With Warm CRPS-1

CRPS-RISE is a Phase 3, multicenter, randomized, triple-blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of intravenous neridronate in approximately 270 participants with warm CRPS-1. Participants are randomized in a 1:1 ratio to receive neridronate or placebo. Eligible patients must meet the Budapest Clinical Criteria for CRPS-1, have experienced a triggering event such as a fracture or sprain, have had the condition for six months or less, and experience moderate to severe pain. The trial also includes selection criteria intended to identify patients who may be more likely to respond, including a positive triple-phase bone scan and features associated with the warm disease subtype. Treatment consists of four intravenous infusions over 10 days, followed by observation through week 12. The primary endpoint measures the change in pain intensity from baseline to week 12 using an 11-point Numerical Rating Scale. Secondary endpoints include additional pain measures and patient-reported outcomes.

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Neridronate Development and Regulatory Significance

Neridronate is a bisphosphonate developed by Abiogen Pharma and is approved and marketed in Italy for CRPS, as well as for osteogenesis imperfecta and Paget’s disease. The company reports that approximately 600,000 patients have received neridronate across its approved indications. In the United States, however, neridronate remains investigational for CRPS-1, and its safety and efficacy for this indication must be established through the clinical development and regulatory review process. The FDA has granted the candidate Breakthrough Therapy, Fast Track and Orphan Drug designations, reflecting its development pathway for a condition with substantial unmet medical need; these designations do not constitute marketing approval. CRPS-1 can develop after limb injuries and may involve persistent pain, swelling, changes in skin temperature and heightened sensitivity. The CRPS-RISE programme also includes long-term outcome tracking and an opportunity for eligible participants with active disease to receive neridronate in an open-label study after completing the main trial. The Phase 3 results will help determine whether neridronate could become an FDA-approved pharmacological treatment for CRPS-1 in the United States.

Source:Ambros Therapeutics, Press release