RECONNECT Trial Results: ZYN002 Does Not Meet Primary Endpoint in Fragile X
Watch the Q&A Recording
Following the RECONNECT result, Dr. Elizabeth M. Berry-Kravis, MD, PhD discusses placebo effects, outcome measures, methylation criteria, and next steps in research.
RECONNECT (ZYN002) Topline Results — September 24, 2025
Harmony Biosciences has announced that the Phase 3 RECONNECT trial of ZYN002 in Fragile X syndrome did not meet its primary endpoint of improving social avoidance in participants, citing a higher-than-expected placebo response. While the results are disappointing, the study adds important knowledge that will inform future clinical research in Fragile X syndrome.
We want to recognize positives that came from RECONNECT:
- It was the first Fragile X trial to successfully implement an at-home/virtual participation option, reducing barriers and expanding access for families who otherwise could not take part. This paves the way for at-home participation in future trials.
- It was a truly global Fragile X trial, with sites across the United States, Australia, Ireland, and the United Kingdom.
Families affected by Fragile X still have no approved treatment. These results — while not what we hoped — move the field forward by teaching us more about trial design, placebo effects, and how best to measure meaningful change in Fragile X.
Continuing the Search for Fragile X Treatments
While ZYN002 did not meet its primary goal, the field continues to advance. Shionogi's large Phase 3 trial of zatolmilast is expected to report results later this year. FRAXA is committed to funding and supporting diverse research strategies, and we will keep the community updated as these and other studies move forward.
Harmony Biosciences: Community Statement and Press Release
