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The trial of the investigational Duchenne muscular dystrophy treatment is the first clinical protocol selected for the FDA's complex innovative trial design pilot program.
Michael Panzara, MD, MPH
A planned phase 2/3 efficacy and safety trial of suvodirsen (WVE-210201) in the treatment of Duchenne muscular dystrophy (DMD) has been selected by the FDA for its complex innovative trial design (CID) pilot program, manufacturer Wave Life Sciences has announced.1
This marks the first time that the FDA has selected clinical protocols for the CID pilot program since it was announced in August 2018. Details of Wave’s Phase 2/3 trial design will be presented at upcoming scientific meetings, according to the company.
“In designing our clinical trials, we are constantly looking to maximize the probability of a definitive result, incorporate the feedback of patients and their families, and reduce the burden on those who are already bravely enduring the challenges associated with serious, genetically-defined diseases. The FDA’s recognition of our plan reflects the thoughtful and collaborative way in which we approach clinical development,” said Michael Panzara, MD, MPH, the chief medical officer of Wave Life Sciences, in a statement.
The FDA considered 2 key criteria for the selection to the CID program: innovative features of the trial design and the therapeutic needs. The application to the program by Wave included its plan to leverage historical control data for DMD to augment the placebo arm of the phase 2/3 trial.
Wave stated that via this pilot program, it intends to “reduce the number of patients required to deliver conclusive clinical efficacy results, thereby minimizing the number of patients required in the placebo treatment arm and potentially accelerating study completion.” The company will additionally support opportunities to discuss the use of Bayesian methods and other design elements of the trial with the FDA to allow for more proficient and dynamic clinical determinations.
“We look forward to further discussions with the FDA in the coming months and sharing learnings from our trial design with others in the rare disease drug development community to drive greater efficiency and productivity in future clinical studies,” Panzara added.
Thus far, suvodirsen, which is an investigational agent for boys with DMD who are amenable to exon 51 skipping, has shown positive results in phase 1 testing.2 The trial assessed 4 primary outcome measures of safety in 40 patients: the number of patients with adverse events (AEs), the severity of those AEs, the number of patients with serious AEs (SAEs), and the number of patients who withdrew due to AEs. Secondary outcomes consisted of the maximum observed concentration (Cmax) at day 1, day 2, and day 8; the time to Cmax (Tmax) at day 1, day 2, and day 8; and the area under the plasma concentration-time curve (AUC0-t) at day 1, day 2, and day 8.
The therapy is additionally being evaluated in an ongoing, multi-dose, open-label extension trial, that began in August 2018 for those completing the phase 1 trial, which Wave has stated it plans to use in its submission for accelerated approval with the FDA. The extension trial is anticipated to read out an interim analysis in the second half of 2019.
The FDA’s CID pilot program is part of the 21st Century Cures Act, with the goal of modernizing clinical trial design, helping to streamline and advance drug development, and more easily inform regulatory decision-making.3
To qualify for the CID pilot program, manufacturers must intend to provide substantial evidence of efficacy through a complex and novel trial design which includes innovative elements such as seamless trial designs, modeling, and simulations to assess trial operating characteristics. Some of the characteristics considered are the use of biomarker enriched populations, complex adaptive designs, Bayesian models and other benefit-risk determinations, among others.
1. Wave Life Sciences Duchenne Muscular Dystrophy Clinical Trial Selected for FDA Complex Innovative Trial Designs Pilot Program [press release]. Cambridge, MA: Wave Life Sciences; Published January 3, 2019. ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-duchenne-muscular-dystrophy-clinical-trial. Accessed January 10, 2019.
2. Wave Life Sciences Announces Positive Phase 1 Results for WVE-210201 in Duchenne Muscular Dystrophy (DMD) [press release]. Cambridge, MA: Wave Life Sciences; Published December 6, 2018. wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-positive-phase-1-results-wve-210201. Accessed January 10, 2019.
3. Complex Innovative Trial Designs Pilot Program. FDA website. Updated December 21, 2018. fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm617212.htm. Accessed January 10, 2019.