Ferrer’s ALS Agent FAB122 Fails to Meet Primary, Secondary End Points

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Despite lack of efficacy in the phase 3 ADORE trial, the oral formulation of edaravone demonstrated safety and tolerability during a 48-week daily dosing period.

 Leonard H. van den Berg, MD, chair of TRICALS—an independent consortium of experts, patients, advocacy groups and foundations from 15 countries in Europe—and professor of neurology at the University Medical Centre Utrecht, the Netherlands

Leonard H. van den Berg, MD

According to a new announcement from Ferrer on the phase 3 ADORE trial (NCT05178810), FAB122, an investigational oral formulation of edaravone, did not meet primary or key secondary end points in patients with amyotrophic lateral sclerosis (ALS). The company also announced the open-label extension ADOREXT study (NCT05866926) will be now concluded, based on the lack of efficacy of FAB122.1

In the ADORE trial, FAB122 did not display significant benefit compared with placebo in slowing disease progression after 48 weeks of daily dosing, as measured by change from baseline in the ALS Functional Rating Scale-Revised (ALSFRS-R) scale score. Investigators also did not observe improvement over placebo on long-term survival with FAB122 as measured by Combined Assessment of Function and Survival (CAFS) score at 48 weeks and 72 weeks in a subgroup of patients. Despite these findings, FAB122 was safe and well-tolerated.1

Top Clinical Takeaways

  • The phase 3 ADORE trial's findings revealed FAB122, an oral formulation of edaravone, did not demonstrate significant benefits in slowing ALS progression compared with a placebo.
  • Principal investigator Leonard H. van den Berg, MD, expressed disappointment but affirmed TRICALS' commitment to ongoing efforts in ALS research.
  • Ferrer, despite acknowledging the unfavorable outcome, remains dedicated to advancing transformative therapies for ALS, emphasizing the importance of continued research in areas of high unmet need.

“At TRICALS, we had hoped for a different outcome of the ADORE study and are disappointed that this is not the positive result we all wanted,” principal investigator Leonard H. van den Berg, MD, chair of TRICALS—an independent consortium of experts, patients, advocacy groups and foundations from 15 countries in Europe—and professor of neurology at the University Medical Centre Utrecht, the Netherlands, said in a statement.1 “We will continue to do our utmost to find a treatment for ALS as soon as possible. We want to thank all the patients who dedicated their time and effort to this trial and Ferrer for the excellent collaboration, which we hope to repeat in the future.”

READ MORE: CNM-Au8 Reduces Neurofilament Light and Improves Survival in ALS, HEALEY-ALS Open-Label Extension Data Suggests

ADORE is a multicenter, multinational, double-blind, randomized, placebo-controlled study that investigated the efficacy and safety of 100-mg FAB122 once daily in patients with ALS. The participants in the study were randomly assigned in a 2:1 ratio to receive either FAB122 or a placebo while also continuing to receive their existing standard of care treatment for ALS. The trial was supported by TRICALS.

“We are disappointed with this outcome and would like to thank the people with ALS, caregivers, investigators and clinical trial staff for their participation in ADORE clinical trial,” Tatjana Naranda, PhD, MSc chief R&D officer at Ferrer, said in a statement.1 “Although the results are not what we hoped for, our work to advance potentially transformative therapies in areas of high unmet need for people living with ALS will not stop.”

Previously established data for a different form of edaravone (Radicava; MT Pharma), suggest the therapy is an effective treatment for ALS. A post-hoc analysis of the phase 3 MCI186-19 study (NCT01492686) published in Muscle & Nerve in 2023 showed a significant reduction in the cumulative occurrence of milestone events such as death, tracheostomy, permanent assisted ventilation (PAV) or hospitalization in patients with ALS treated with edaravone. The data compared those who continued with edaravone for an additional 24 weeks (edaravone-edaravone [EE] group: n = 65) after the 24-week double blind period and those who switched from placebo to active treatment at the 24-week mark (placebo-edaravone [PE] group; n = 58). All told, investigators observed a 53% relative risk reduction of milestone events in the EE group vs PE group at the 48-week point, with a hazard ratio (HR) of 0.47 (95% CI, 0.25-0.88; P = .02).

Overall, the study was further supported by the Cox PH model survival curve, where a significant separation in clinical curves for time to the cumulative end point of death, tracheostomy, PAV, or hospitalization was observed between the groups. Reanalyzing the Study 19 trial data according to the ALS/standard uptake ratio value composite end point demonstrated a statistically significant treatment benefit for the EE group compred with PE group at week 24 (0.15 [±0.05]; 95% CI, 0.06-0.25; P <.01) and week 48 (0.11 [±0.05]; 95% CI, 0.02-0.21; P = .02).

REFERENCES
1. Ferrer Reports Top-Line Results from Phase 3 ADORE Study in ALS. News Release. Ferrer. Published January 10, 2024. Accessed January 15, 2024. https://ala.associates/clinical/ferrer-reports-top-line-results-from-phase-iii-adore-study-in-als/

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