2016 SMA Researcher Meeting Summary: The Changing Landscape of SMA

The SMA Researcher Meeting is the largest research meeting in the world specifically focused on SMA. This year we had a record setting 350 attendees. The goal of the meeting is to create open communication of early, unpublished scientific data, accelerating the pace of research. The meeting also furthers research by building productive collaborations—including cross-disciplinary dialogue, partnerships, integration of new researchers and drug companies, and educational opportunities for junior researchers.

We will be posting a series of summaries from our 2016 researcher meeting, highlighting some of the most interesting new developments and discoveries presented there. This update covers the special session, “The Changing Landscape of SMA: Consideration of Future Needs,” moderated by Cure SMA Scientific Advisory Board Member Stephen Kolb MD, PhD (Ohio State University).

With the recent announcement that nusinersen will be submitted for FDA approval, and with other SMA drug programs progressing through clinical trials, opportunities such as this panel, “The Changing Landscape of SMA,” are critical to shaping the next phase of SMA research and care.

Dr. Kolb began by introducing the session goal: to discuss the changing landscape of SMA. He asked the group to imagine a future when the first drug approvals for SMA therapies have occurred, and the implications that might have for basic research, drug development, and clinical care.

Overall, the session emphasized how to move towards effective drug treatments and improved quality of life for patients with all types of SMA and at all stages of disease progression. The session also included discussion of approval of second in class drugs (meaning new drugs that are approved after the first drug is approved), the use of combination therapies, and the importance of patient registries and standards of care.

Because drugs in the SMA pipeline may not be wholly sufficient therapies for all patients, there is a need for development of multi-drug (combination) therapies. In the talk given by Heather Clark, MS, (Vertex Pharmaceuticals) SMA researchers and clinicians were able to learn from the experience of a different disease community. Ms. Clark shared her team’s efforts to develop a combination therapy for cystic fibrosis and their regulatory strategies used to obtain approval. She also discussed the fact that FDA guidance exists for toxicological evaluation and clinical testing of combination therapy. This differs by type of combination therapy being tested and stage of development. Their work offered many valuable strategies that can also be applied to SMA therapies in order to expedite combination drug development.

Continuing with the same topic, Karen Chen, PhD, (SMA Foundation) gave a talk about considerations for developing combination therapies for SMA. As the SMA drug pipeline expands and grows in diversity and complexity, Dr. Chen explained how the biological rationale and therapeutic need for multiple therapeutic approaches and combination therapies has become increasingly apparent. However, care and consideration must be applied anytime multiple drugs are given to the same patient. Understanding how the drugs work both individually and together and how they affect their targets is important for safety and efficacy.

Next John Porter PhD (Myotonic Dystrophy Association) shared lessons learned form the first NDA (new drug application) submissions in DMD (Duchenne muscular dystrophy). These lessons help to inform the SMA community as it seeks to bring new drugs through clinical trials and ultimately to patients. Understanding how to best navigate the FDA approval process and increase the chances of successful drug approval is of great importance as more and more drugs enter clinical trials for SMA.

Dr. Porter discussed a number of issues that are critical to obtaining successful drug approval, by highlighting the FDA response to three different new drug applications (NDAs) in in DMD. This included discussion on the importance of:

  • Calculating the strength of the drug’s effect in primary outcome measures;
  • Properly validating the outcomes measures;
  • Understanding the natural history around these outcome measures, through validation of biomarkers, adequate trial size, correct inclusion and exclusion criteria, and the use of placebo controls; and
  • Using partnerships to secure expertise and resources.

Katherine Klinger, PhD, (Genzyme Corporation) focused on the important of registries in rare disease. In general registries aim to:

  • Facilitate patient recruitment for clinical trials;
  • Accelerate research into new therapies by helping to better understand the disease and develop new research methods;
  • Help gain more knowledge on real world and long-term consequences of a drug therapy, such as changing natural history, new safety findings, and newly emerging complications;
  • Learn about how differential clinical care impacts disease progression and inform care management guidelines, to help achieve optimal and equal care for all patients;
  • Provide a link to the community and provide patients with information directly relevant to their condition and treatment.

Dr. Klinger shared how other rare disease communities; such as cystic fibrosis, Pompe disease, and Guacher disease, have learned and benefited from registries and how registries could potentially benefit the SMA community. For instance in cystic fibrosis, data from their registry has helped dramatically improve lung function and life span over the past 20 years.

The last talk was given by Richard Finkel, MD, (Nemours Children’s Hospital). Dr. Finkel discussed the use of natural history data to inform the standardization of patient care. Standards of Care (SOC) guidelines were developed in 2007 with the goal of providing optimal care and the best quality of living possible for the patient. Up-to-date and well-defined SOCs can also impact drug development as patients following SOC guidelines have often received similar care, reducing clinical trial variability. However, it is also important to note that SOCs are guidelines, not rules, and each family maintains the right to determine what care is best for them. SOCs are continually changing as better care is developed and new therapies emerge. Currently, Dr. Finkel is leading an international effort to update the standards of care for SMA to reflect our current knowledge. He expects those to release later this year.

Finally, Dr. Kolb led a panel discussion between the session speakers and the panelists. Important future directions for our community were outlined, such as:

  1. Identifying novel drug targets for SMA to advance combination therapies to ensure treatments for all age, stages, and types of SMA. This includes support for basic research into the biology of SMN and motor neurons.
  2. Ensuring we have outcome measures or means that will allow drug approvals for all SMA types and ages.
  3. Patient focused drug development efforts, to inform regulators on clinical meaningfulness and risk/benefit from the patient perspective.
  4. Post-marketing registries to collect long-term information on drug efficacy and clinical care.
  5. Determining and disseminating standards of care, both for clinical trials and overall care.
  6. Reducing the time to diagnosis with newborn screening and/or physician awareness efforts.
  7. Finding ways to make current drug candidates more openly available for preclinical research, by encouraging collaboration between industry partners.

For More Information

For more information on how Cure SMA is working on these important future directions for our community, please see these recent articles from our news section.


Pictured above: Dr. Katherine Klinger speaks at the special session.

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