30 Apr Spinal Muscular Atrophy: Biogen Enrolls First Patient in Higher-Dose SPINRAZA® (NUSINERSEN) Study

MedicalResearch.com Interview with:

Dr. Ferguson

Toby Ferguson, M.D., Ph.D.
Vice President, Head Neuromuscular Development Unit
Biogen

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by SMA, who is primarily affected and incidence?

Response: Spinal muscular atrophy (SMA) is a rare, genetic, neuromuscular disease characterized by a loss of motor neurons in the spinal cord and lower brain stem that can result in severe, progressive muscle atrophy and weakness. Approximately one in 10,000 live births have a diagnosis of SMA. It is a leading genetic cause of infant mortality; however, people of all ages are impacted by the disease.

More than three years ago, SPINRAZA (nusinersen) became the first FDA-approved treatment option for SMA.

The DEVOTE study, which recently treated its first patient, is designed to evaluate the safety and potential for even greater efficacy of SPINRAZA when administered at a higher dose than currently approved for the treatment of SMA. The Phase 2/3 randomized, controlled, dose-escalating study will be conducted at approximately 50 sites around the world and aims to enroll individuals of all ages with SMA.

MedicalResearch.com: How does nusinersen differ from other treatments for SMA?

Response: SPINRAZA combines sustained efficacy and a well-established long-term safety profile as demonstrated through its clinical development program, which has included a broad range of people with SMA, some of whom have been treated for up to six years. As of March 31, 2020, more than 10,000 people of all ages with SMA, including commercial patients, early access patients and clinical trial participants, had been treated with SPINRAZA in more than 50 countries.

Due to differences in administration, clinical trial design and studied populations, it is difficult to draw direct comparisons between SPINRAZA and other treatments. However, SPINRAZA is administered into the fluid surrounding the spinal cord where motor neurons reside to deliver the treatment where the disease starts.

MedicalResearch.com: What are the main findings of previous studies?

Response: SPINRAZA was evaluated in two Phase 3 randomized, double-blind, sham-controlled studies of infantile and later-onset SMA (ENDEAR and CHERISH, respectively) and supported by open-label studies that include pre-symptomatic infants (NURTURE), individuals with later-onset SMA (CS2/CS12) and an extension study of individuals who previously participated in the clinical development program (SHINE).

Clinical results to date include:

• The pivotal Phase 3 studies, ENDEAR and CHERISH, evaluated the safety and efficacy of SPINRAZA for patients with infantile-onset and later-onset SMA, respectively. In the ENDEAR study (n=122), treatment with SPINRAZA resulted in a statistically significant 47 percent reduction in the risk of death or use of permanent assisted ventilation, and in the CHERISH study (n=126), a higher proportion of trial participants had attainment of new motor milestones and greater increases in upper limb motor function among patients treated with SPINRAZA compared to untreated patients.
  • The most common adverse events observed were respiratory infection, fever, constipation, headache, vomiting and back pain.
• In the NURTURE supportive open-label study (n=25), treatment with SPINRAZA prior to the onset of clinical symptoms resulted in survival of 100 percent of infants, with none requiring permanent ventilation. In comparison to the natural history of SMA, many of these infants would likely have passed away or required permanent ventilation, on average, by 13.5 months. The findings are aligned with previous safety findings with no new safety concerns identified.
• In the CS2/CS12 supportive open-label study (n=47), treatment with SPINRAZA resulted in motor function improvements and disease activity stabilization, suggesting that SPINRAZA may not only prevent motor function deterioration, but could also allow for continued motor function improvement and even reversal of motor function loss.
• In the SHINE extension study, participants with later-onset SMA originally enrolled in CS2/CS12 (n=24 in this analysis) experienced improvements or stabilization in measures of motor function for up to nearly six years, in contrast to the expected decline observed in natural history cohorts. The findings are aligned with previous safety findings with no new safety concerns identified.

MedicalResearch.com: Can you share additional details about the DEVOTE study design? 

Response: DEVOTE is a three-part study that will include an open-label safety evaluation cohort and a pivotal, double-blind, active control randomized treatment cohort followed by an open-label treatment cohort. After the safety evaluation cohort completes, the pivotal cohort will begin and include a treatment group receiving two loading doses of 50 milligrams (mg) 14 days apart, followed by a maintenance dose of 28 mg every four months. A second treatment group will receive the current U.S. Food and Drug Administration-approved administration of SPINRAZA, which is four loading doses with 12 mg maintenance doses every four months. The third cohort will be an open-label evaluation to assess the safety and tolerability of transitioning patients from the currently approved dose of SPINRAZA to the higher dose being tested in the study. More information is available on www.clinicaltrials.gov (NCT04089566). 

MedicalResearch.com: Is there anything else you would like to add?

Response: SPINRAZA is the only treatment currently approved for infants, children and adults with SMA and has real-world experience in a broad age range of individuals. Ongoing research like the DEVOTE study is instrumental to help deepen our understanding of the disease and potentially further improve what it means to live with SMA. 

Citation:

Biogen announcement that the first patient has been treated in a new Phase 2/3 clinical study, DEVOTE, to evaluate the safety, tolerability and potential for even greater efficacy of SPINRAZA (nusinersen) when administered at a higher dose than currently approved for the treatment of spinal muscular atrophy.
http://investors.biogen.com/news-releases/news-release-details/biogen-announces-first-patient-treated-higher-dose-spinrazar

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Last Updated on April 30, 2020 by Marie Benz MD FAAD