FSHD Society, C-Path Gathering Trial Data on Placebo Group Patients

The FSHD Society has joined forces with the Critical Path Institute (C-Path) to facilitate the collection of data from people with facioscapulohumeral muscular dystrophy (FSHD) who were given a placebo in previous clinical trials.

Provided by sponsors of FSHD trials, the data will be integrated into C-Path’s Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP), an initiative funded by the U.S. Food and Drug Administration for rare disease characterization and therapy development acceleration.

Integration of the trial data into RDCA-DAP will allow the analysis of information from a larger number of patients, helping to gain a better understanding of FSHD’s natural course.

“RDCA-DAP promotes the sharing of existing patient-level data and encourages the standardization of new data collection,” Alexandre Bétourné, PhD, the scientific director of RDCA-DAP, said in a press release. “By integrating such data in a regulatory-grade format suitable for analytics, RDCA-DAP helps accelerate the understanding of disease progression, clinical outcome measures, and biomarkers, and facilitates the development of mathematical models of disease and innovative clinical trial designs.”

“This is particularly important in rare diseases like FSHD that progress at slow and unpredictable rates,” the society stated in the release.

To date, organizations participating in this initiative include Acceleron Pharma, now part of Merck — known as MSD outside North America — and the University of Rochester in New York.

Acceleron is contributing control data from a two-part Phase 2 clinical trial (NCT02927080) that evaluated the safety and effectiveness of its investigational therapy ACE-083 in adults with FSHD who had muscle weakness affecting the calf and/or bicep muscles.

ACE-083, injected directly into the affected muscles once every three weeks, was designed to increase muscle strength and function.

In the study’s second part, 58 participants were assigned randomly to either ACE-083’s optimal dose, defined during the trial’s first, ascending-dose part, or a placebo for six months.

Final data from the trial, which ended in October 2019, showed that ACE-083 was generally well-tolerated and superior to placebo at significantly increasing muscle mass — meeting the study’s main goal.

However, these benefits did not translate into significant improvements in muscle function as assessed by multiple tests and patient-reported outcomes, failing to attain the trial’s secondary goals.

Based on these results, Acceleron decided to discontinue ACE-083’s clinical development for FSHD. The company will provide data from placebo group patients, including total muscle volume measured by MRI and quantitative testing of muscle strength.

The University of Rochester sponsored a trial, concluded in 2015, testing albuterol against a placebo in 90 adults with FSHD.

Albuterol, also known as salbutamol, is an approved inhaled therapy for asthma due to its airway-widening effects based on the relaxation of muscle cells. Animal and human studies also suggested that this type of molecule, which activates a cell surface receptor called beta-2 adrenergic receptor, could increase muscle mass or prevent muscle wasting.

Data collected in this study included muscle contraction testing and muscle mass assessments, and those findings in patients assigned to a placebo will be integrated in RDCA-DAP.

“We are grateful to Acceleron and the University of Rochester,” said Jamshid Arjomand, PhD, FSHD Society’s chief science officer. “Their leadership in the effort to share meticulously collected clinical data to help advance the field of FSHD and future clinical trial design should be applauded.

“We look forward to expanding the FSHD database in RDCA-DAP as new studies generate additional clinical data,” Arjomand added. “Over time, this project will lead to insights that will improve the design of clinical trials for FSHD.”

Bétourné said: “This is a great example of how we can collaborate to help accelerate drug development for rare diseases. The FSHD society included their community in discussions, landscaped the accessible data and simultaneously engaged C-Path and multiple data contributors, which expedited the sharing of these two datasets.”