Cure SMA Details Its ‘Clinical Trial Readiness Program’

A readiness program to help clinical trial sites prepare to run spinal muscular atrophy (SMA) studies has been established by Cure SMA in collaboration with the pharmaceutical industry, other patient advocacy groups, and research institutes.

The program is described in a position statement, “The SMA Clinical Trial Readiness Program: creation and evaluation of a program to enhance SMA trial readiness in the United States,” published in the Orphanet Journal of Rare Diseases.

Clinical trials are necessary to test whether potential treatments for diseases are effective and safe, but require both resources and expertise. This is particularly true of a complex and rare disorder like SMA.

The past decade has seen an explosion in SMA research, and the approval of two disease-modifying treatments — Spinraza by Biogen, and Zolgensma by Novartis and AveXis — with a third, risdiplam, by Roche, under review by the U.S. Food and Drug Administration.

At least half a dozen potential SMA treatments are also moving through clinical trials, with many more in development.

To help prepare sites, and to address the “scientific, clinical, and regulatory challenges associated with SMA therapeutic development and evaluation,” Cure SMA began working with members of industry and others to develop the SMA Clinical Trial Readiness Program.

“This program provides US-based clinical research sites with resources to evaluate and optimize their readiness for SMA trials,” the statement’s five authors — two with CureSMA and three with a law firm — wrote. “Its ultimate goals are to alleviate challenges related to site capacity and trial access within the US, while sensitizing sites to the evolving needs of SMA patients and families.”

The paper described the development of the program, which occurred in three phases.

The first phase was a landscape assessment, carried out in 2017. This involved working with sites that had already been involved in SMA clinical trials to best understand what factors — from staff expertise and education to clinical infrastructure —were important for successful trials.

Mathematical modeling suggested that, from 2018–22, these existing sites would need to double the number of patients recruited in order to adequately test the treatments expected to enter clinical development. As this is not really feasible — due to costs, geographical constraints, and other strains — this finding highlighted a need to expand clinical trial sites for SMA.

The second phase was developing the program, using information gleaned from its first phase. Ultimately, the program that was developed had three basic components: one, an evaluation to assess overall site readiness; two, an in-depth document to give research teams practical information about SMA and conducting patient-centered trials; and three, an educational program for physical therapists and clinical evaluators, who are particularly crucial for successful trials.

The third and final phase was a pilot program. Cure SMA announced the program in early 2018. By the start of 2019, nine sites had voluntarily completed the program.

Feedback collected from these sites was generally positive. “Responses to a program survey completed by five pilot sites indicated that the program had helped all respondents in some way,” the authors wrote. Responses also indicated that program information could be incorporated into actual clinical practice.

The program was then further refined, streamlined, and expanded using feedback from the pilot study. Four additional sites completed the program in 2019, and new educational material has been created. Program resources were made available online, and Cure SMA is collaborating with SMA Europe to expand the program to countries there.

“Cure SMA’s Clinical Trial Readiness Program represents … a unique example of a patient advocacy group establishing a program in a collaborative setting with pharmaceutical sponsors, other patient advocacy organizations, and research hospitals,” the authors wrote. They noted that this model could be applied to other rare diseases.

Several challenges in SMA trials were also highlighted, mainly in terms of clinical and research expertise in a complex rare disease like SMA, and site and staff resources.

“While Cure SMA’s resources help to fill a gap for SMA clinical trials, resources for learning about rare diseases and unique considerations for managing trials within these diseases often do not exist,” the paper stated.

Still, “this program has created a new means for engaging research sites interested in SMA trials, providing tangible resources to optimize readiness, promote patient-centered trial management, and increase sites’ visibility with sponsors,” the authors concluded.

To “ensure sustained relevance,” Cure SMA will continue to adapt it to future sponsor and site needs.

“Implementation of this model has potential to amplify the patient voice and promote more patient-centric clinical trial management, by sensitizing sites to unique needs of specific patient communities,” the authors concluded.