Changing Therapeutic Landscape of Spinal Muscular Atrophy: DMTs Show Promise

Because there is not currently a cure for spinal muscular atrophy (SMA), research continues for innovative gene therapy options to help manage and care for afflicted patients.

In an interview with First Report Managed Care, Omar Dabbous, MD, MPH, vice president of global health economics and outcomes research, Novartis Gene Therapies, discusses his focus on evidence generation for Zolgensma, a transformative gene therapy to treat SMA. “My goal is to demonstrate the clinical, humanistic and economic value of gene therapy; as well as differentiate and support reimbursement initiatives to ensure patients can access treatment as quickly as possible after a diagnosis,” said Dr Dabbous.

What existing data led you and your co-investigators to conduct this research?

As a rare genetic neuromuscular disorder, treatment options for SMA before disease-modifying therapies (DMTs) were rather limited. The conventional care largely focused on nutritional and respiratory care, physiotherapy, and strategies to maintain independent living. However, these methods don’t tackle the mechanism of disease, which historically left the neuropathologic process, and hence neuromuscular function of the patients, largely unchanged. With the advent of 3 DMTs for SMA over the past few years, we have seen inspiring efficacy and safety data reported from the clinical trials, suggesting these treatments could potentially transform the prognosis of these patients. 

In collaboration with Min Yang, MD, PhD, Vice President at Analysis Group, Inc, Adjunct Assistant Professor at the University of Texas at Austin, College of Pharmacy, we felt it was time to have a comprehensive review of evidence from the literature to date to provide a landscape synthesis of the natural history of SMA, as well as the profiles of the treatment options on efficacy and safety, health-related quality of life, and economic impacts, with an emphasis on DMTs.  

Please briefly describe your study and its findings. Were any of the outcomes surprising?

Through the systematic reviews of the literature, we observed a changing therapeutic landscape with a variety of interventions evaluated in clinical studies for SMA. Recent literature has more reporting on the available DMTs, showing improvements in survival and motor function. Given the nature of the disorder, long-term impact on a patient’s function and quality of life are critical, but are also difficult to obtain, as the first DMT was approved less than a decade ago. 

On the other hand, substantial methodological heterogeneity was found during our review, including reporting from clinical trials which showed inconsistency in endpoint definitions and variations in measurement tools. The lack of homogeneity of the underlying approaches for data generated across the studies prevented us to conduct meaningful quantitative synthesis, such as meta-analysis, of the findings. 

How can payers use this information in formulary decision making?

Current treatment options for SMA are revolutionary to the patients in need, and additional data—apart from safety and efficacy evidence from clinical trials—can help more comprehensively inform payers in their decision making. The information to come out of studies on newborn screening (NBS) for SMA is a key example. NBS allows for the detection and diagnosis of SMA in infants, via a simple heel-prick blood spot test performed at birth. Families are then able to move forward with a DMT plan just days or weeks after birth, often before symptoms have even appeared. This early intervention can have a profound impact on neurodevelopmental outcomes for the patient. More of this type of research is needed for payers to gain an in-depth understanding on the burden of illness (natural history, economic and humanistic), and an up-to-date review of the therapy options. 

Do you and your co-investigators intend to expand upon this research?

New data on patient experience with the 3 DMTs for SMA is still emerging, including long-term follow up studies, and payers will look to this evidence for a comprehensive view on the landscape. Expansion of this research by the industry at large will be important not just for payers, but for all stakeholders, to ensure the continued evolvement of therapeutic options.

Is there anything else pertaining to your research and findings that you would like to add?

The variability observed through our research highlights the need for consistent and standardized endpoint assessment approaches and reporting for safety and efficacy outcomes in clinical trials. This can allow for meaningful indirect treatment comparisons across therapies when head-to-head trial data are not available. For the DMTs, long-term data are warranted from the patients treated with such therapies to appreciate the real-world outcomes of patients over time.

About Dr Dabbous

Dr Omar Dabbous is the vice president of global health economics & outcomes research (HEOR) and real-world evidence (RWE) for Novartis Gene Therapies where he is a key member of the leadership team in a role of high visibility and strategic importance. He is responsible for setting the global HEOR &RWE research strategies and tactics spanning in the USA, Europe, Latin America, and Asia-Pacific for gene therapy. Areas of history responsibilities include Medical Affairs, Clinical Development, Commercialization, Analytical Thought Leadership, and Market Access with emphasis on ensuring evidence generation and communication plans are aligned across the global organization. Dr Dabbous is a key part of the team to launch the first-ever gene therapy drug for SMA. Dr Dabbous has launched over 15 pharmaceutical and medical device products. He has been recognized as one of the Top 50 Most Influential People in Big Data.