Phase 3 ADORE Trial of FNP122 in ALS Enrolls First Patient

The trial is anticipated to enroll 300 patients with amyotrophic lateral sclerosis in Europe to evaluate the safety and efficacy of oral edaravone.

The first patient with amyotrophic lateral sclerosis (ALS) has been enrolled in the ALS Deceleration with Oral Edaravone (ADORE) phase 3 trial of FNP122, an oral formulation of edaravone (Radicava; Mitsubishi Tanabe Pharma America), Ferrer Pharma announced. The trial is set to enroll approximately 300 patients throughout Europe to evaluate the safety, survival, and efficacy of FNP122.1

“ALS had a profound impact on the lives of people diagnosed with the disease, as well as their loved ones,” Rodrigo Palma dos Reis, chief medical officer, Ferrer, said in a statement.1 “We feel a great sense of purpose and responsibility to develop this potential therapy with the aim of improving the current standard of care.”

TRICALS, a European research initiative aimed at finding a cure for ALS, has supported the phase 3 trial. In the statement, Leonard H. van den Berg, MD, chair, TRICALS; professor of neurology, University Medical Centre Utrecht, The Netherlands; and principal investigator of the ADORE study expressed the consortium’s pride in the collaboration with Ferrer, calling the study “important,” and adding that the group “look[s] forward to offering further support throughout the course of the trial. We hope oral edaravone will yield a positive outcome and be beneficial for people diagnosed with ALS, as more effective treatment is available”.

The announcement coincides with Ferrer’s announcement of a license agreement with Treeway—a Dutch-based biotechnology company—for both the development and commercialization of FNP122 (formerly TW001). This will take place in specific territories, specifically Europe and parts of Asia. 

“Ferrer cares deeply about patients affected by ALS and meeting their needs is the major driving force behind this study,” Tatjana Naranda, chief R&D officer, Ferrer, added in a statement.1 “FNP122 is aimed at transforming the lives of patients who suffer from ALS, and we have made a strong commitment to deliver therapeutic solutions to patients and their families.” 

READ MORE: Phase 3 PHOENIX Study of AMX0035 in ALS Gets Under Way

Previous Studies of Edaravone

Edaravone research has shown that the antioxidant and free radical scavenger reduces excess oxidative stress, as well as cell death. Data from Study 19 (NCT01492686), presented at the Muscular Dystrophy Association’s Scientific and Clinical Conference 2021, March 15-18, 2021, suggested early intervention with intravenous (IV) edaravone reduced death, tracheostomy, permanent assisted ventilation, and hospitalization in patients with ALS.2

During the 24-week double-blind period of edaravone vs placebo, no new deaths occurred. During the open-label period, 2 deaths (2.9%) occurred in the edaravone-to-edaravone (EE) group, and 4 deaths (5.9%) occurred in the placebo-to-edaravone (PE) group. HRs for death were 0.48 (95% CI, 0.08-2.73; P = .4059) in the EE compared to the PE group.

First author Benjamin Brooks, MD, medical director, Atrium Health Neurosciences Institute, Carolinas Medical Center, and colleagues determined the HR for the cumulative occurrence of death, tracheostomy, or permanent assisted ventilation to be 0.44 (95% CI, 0.10-1.81; P = .2523) in the EE group (n = 3; 4.3%) compared to the PE group (n = 6; 8.8%). Adding hospitalization to the cumulative survival analysis yielded a statistically significant HR of 0.47 (95% CI, 0.25-0.88; P = .0189) in the EE group (n = 20; 29.0%) compared to the PE group (n = 27; 39.7%). 

The study also found a least square mean change of –5.01 (standard error [SE], 0.64) from baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) scores in the edaravone group compared with a change of –7.50 (SE, 0.66) in the placebo group. That 2.49-point difference (SE, 0.76 [95% CI, 0.99-3.98]; P = .0013) represented a 33% improvement in ALSFRS-R in patients with reduced forced vital capacity (FVC) of <80% prior to starting edaravone versus placebo.3

Edavarone was also shown to be effective in reducing ALSFRS-R score, regardless of FVC, according to findings from a post hoc analysis. Through 48 weeks, patients in both bulbar and limb-onset groups experienced a reduction in ALSFRS-R score loss versus placebo following treatment. Patients with bulbar-onset ALS with either >80% or <80% experienced similar ALSFRS-R scores, indicating the drug’s efficacy regardless of FVC.4

REFERENCES
1. First patient enrolled in Ferrer’s FNP122 ADORE phase 3 clinical trial for amyotrophic lateral sclerosis (ALS) treatment. News release. Ferrer. November 9, 2021. Accessed November 9, 2021. https://www.ferrer.com/en/node/3250
2. Brooks BR, Sakata T, Takahashi F, et al. Early intervention with edaravone in study 19 was associated with decreased hospitalization, tracheostomy, ventilation, and death in patients with ALS. Presented at MDA Clinical and Scientific Conference 2021; March 15–18. Poster 57.
3. Safety and efficacy of edaravone in well-defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(7):505-512. doi:10.1016/S1474-4422(17)30115-1
4. Pattee G, Suarez Zambrano G, Zhang J, Nelson S, Apple S. Post hoc analysis of edaravone study 19: efficacy in bulbar onset ALS patients with and without reduced pulmonary function. Presented at: 2020 MDA Clinical & Scientific Conference. Abstract 53.