Top 10 SMA Stories of 2019

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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top 10 of 2019

SMA News Today brought you daily coverage of key findings, treatment developments  — including in-depth coverage of Zolgensma’s approval in the U.S. — and of clinical trials related to spinal muscular atrophy (SMA) throughout 2019.

We look forward to reporting more of this relevant news to patients, family members, and caregivers dealing with SMA during 2020.

Here are the top 10 most-read articles of 2019, with a brief description of what made them relevant for the SMA community.

No. 10 — “Belgian Neurologist Led Efforts to Bring Spinraza to Polish Kids with SMA

Laurent Servais, a renowned Belgian neurologist and SMA expert, helped several Polish patients obtain early access to Biogen’s Spinraza (nusinersen) — the first approved treatment for the disease — before its European Union approval in June 2017. Based in Paris, Servais was treating SMA type 1 patients under a special French early access provision that allowed these patients to receive Spinraza months before its approval. News of Servais’ work led to requests from around the world, including Poland, for him to treat SMA type 1 patients. With the help of Karolina Aragon, a Polish neurologist, the two treated dozens of Polish SMA patients in the two years before the country’s health insurance fund agreed to cover Spinraza. Servais also helped Poles get early access to other SMA therapies, including Roche’s risdiplam, which is still in clinical trials.

No. 9 — “Risdiplam Raising SMN Levels in Older Patients in Ways That Seem Durable, Researcher Says of Early Trial Data

In a July interview, Claudia A. Chiriboga, MD, the lead investigator of the open-label, Phase 2 JEWELFISH study (NCT03032172) evaluating risdiplam in SMA patients, discussed early data from the first 12 people enrolled. With a median age of 20 (ranging from 13 to 52 years old), six had SMA type 2 and six had type 3. Early results showed that treatment with risdiplam — being developed by Roche and Genentech in collaboration with PTC Therapeutics — for a median of 14 months led to sustained increases in blood levels of SMN, the missing protein in SMA patients. While at the time there were no data on the clinical significance of these increases in SMN blood levels, Chiriboga believed they would reflect higher levels of SMN in the central nervous system (spinal cord and brain; CNS), as observed in animal models of SMA. Chiriboga also emphasized the therapeutic potential of risdiplam as an oral therapy that can reach all tissues and organs, including the CNS. “I am persuaded myself … that [systemic delivery] is one of the reasons why [risdiplam] works so well in these infants,” she said, while commenting on the results from the Phase 2/3 FIREFISH trial (NCT02913482) showing that most of its 21 SMA type 1 infants had meaningful motor improvements at 12 months of treatment.

No. 8 — “Higher Doses of Spinraza To Be Tested in New Phase 2/3 Trial

In September, Biogen announced its plan to initiate a global Phase 2/3 clinical trial (NCT04089566), called DEVOTE, to evaluate whether higher doses of Spinraza promote greater motor improvements in up to 126 people with infantile- or later-onset SMA. DEVOTE will also assess the safety, tolerability, and pharmacokinetics (uptake, distribution, and elimination in the body) of those higher doses: 28 mg and 50 mg loading doses, compared with the approved 12 mg dose. For more information on patients’ eligibility and contacts of the trial, which is expected to begin recruiting in late February, click here.

No. 7 — “Zolgensma ‘Saved All of Our Lives’: A Family’s Journey Through Gene Therapy

In a phone interview with SMA News Today, Tina and Torence Anderson shared their son’s journey with SMA and how NovartisZolgensma changed their lives. In 2015, 3-month-old Malachi was diagnosed with SMA type 1. Despite a doctor’s “advice” to just take their son home and love him, the couple was willing to do whatever they could to help him. Soon they found the pivotal Phase 1 clinical trial (NCT02122952) evaluating investigational Zolgensma (then known as AVXS-101) gene therapy in babies with SMA type 1. About a month after his diagnosis, and after a battery of tests confirmed his eligibility, Malachi received the single one-hour intravenous (into-the-vein) infusion of Zolgensma. According to the parents, improvements were evident almost immediately. Malachi “always gained [in motor skills]; he’s never had any plateaus, he’s never lost any strength. … We’re very happy with Zolgensma being his only treatment for now,” Tina said, adding that Zolgensma “didn’t only save Malachi. It saved all of our lives.”

No. 6 — “Rural Pennsylvania Clinic Treats Amish, Mennonite Children Who Have SMA

In the beginning of the year, we reported the work that takes place in the Clinic for Special Children (CSC), just outside Strasburg, Pennsylvania. CSC belongs to the Plain Community Health Consortium, a group of five clinics in Delaware, Indiana, Ohio, Pennsylvania, and Wisconsin that serve Amish and Mennonite populations. Due to their limited number of founders and their tradition of marrying people from the same community, these populations have a limited genetic variability and are at a greater risk of some genetic diseases. SMA affects about five times more people in these two communities than in the general U.S. population. The clinic — which does not work with insurance companies — provides SMA genetic testing, diagnosis, and counseling at an incredibly low price, compared to conventional clinics. “The reason why we can provide these services is through philanthropy and support, from both inside and outside the community,” said Adam Heaps, CSC’s executive director. The CSC is also the only site in Pennsylvania participating in the Phase 3 SPR1NT study (NCT03505099), which is evaluating Zolgensma in asymptomatic SMA type 1, 2 and 3 babies.

No. 5 — “How Zolgensma Works and Trials Underway in Range of SMA Patients

After Zolgensma’s U.S. approval to treat SMA in infants and children under age 2, we explored its mechanism of action as well as its ongoing trials. Zolgensma, a gene therapy developed by AveXis (which was acquired by Novartis in 2018), works by delivering a healthy copy of the SMN1 gene — which is mutated in SMA patients — directly into motor nerve cells. This delivery is carried out using a harmless version of an adeno-associated virus subtype known as AAV9, which was shown to be highly effective in targeting brain and spinal cord cells in preclinical studies. By administrating AAV9 directly into the bloodstream or the spinal canal, this one-time treatment is expected to deliver a functional SMN1 gene to motor nerve cells, which then start to produce SMN protein immediately and continuously. Four Phase 3 clinical trials (NCT03306277; NCT03461289; NCT03837184; NCT03505099) and one Phase 1 study (NCT03381729) were at publication time evaluating the therapeutic effects of Zolgensma in babies and children with SMA type 1 and 2.

No. 4 — “SMA Newborn Screening Expands as More States Enact Mandatory Testing

By March 2019, five states — Missouri, Minnesota, New York, Pennsylvania and Utah — were routinely screening newborn babies for SMA, while another 13 had begun pilot screening or were considering doing so. Missouri was the first state to establish SMA genetic screening in 2017, with Utah soon following its steps. With two therapies — Spinraza and Zolgensma — now available to treat SMA, neurologist Jerry Mendell of Nationwide Children’s Hospital in Columbus, Ohio, who played a key role in the development of Zolgensma, said that more and more states see the logic in testing for a disease that was considered incurable not long ago. Arndt Rolfs, CEO of Centogene — a German diagnostics company that specializes in genetic testing for rare diseases — added that it is crucial to test patients “at the very beginning, before an individual might develop the risk for specific symptoms.”

While SMA was first nominated to be included in the Recommended Uniform Screening Panel (RUSP) in November 2008, it was only officially added in July 2018. States that had begun or considered pilot screening included Arkansas, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Massachusetts, New Hampshire, North Carolina, Ohio, Texas and Wisconsin.

No. 3 — “With Zolgensma’s Approval, Debate Shifts to Pricing and Availability of World’s Costliest Drug

While Zolgensma’s approval brought hope to the SMA community, its elevated price led to several debates. With a price tag of $2.125 million, it is by far the world’s most expensive one-time therapy. “We are deeply concerned about the price of this product — both from the perspective of the individual patient and the healthcare system overall,” Rachel Sher, National Organization for Rare Disorders (NORD)’s vice president for regulatory and government affairs, told SMA News Today in a comment email. To reduce the economic burden, payers have the option of paying $425,000 a year for five years. Dave Lennon, the president of AveXis, Novartis subsidiary, said the price is also “backed by five-year, outcomes-based agreements that payers can employ, and allows for rebates should the product not perform as expected.” Company officials also noted that Spinraza treatment can cost nearly twice as much — $4.125 million — over a 10-year period. Researchers and pharmaceutical companies are currently working on ways to reduce the manufacturing costs of this type of gene therapies.

No. 2 — “Zolgensma Could Be More Cost-effective than Spinraza with One-time $2 Million Price, Report Says

preliminary Draft Evidence Report from the Institute for Clinical and Economic Review (ICER) suggested that  Zolgensma could be more cost-effective than Spinraza with a one-time price of $2 million. ICER is a non-profit and independent agency that evaluates the value of prescription medicines and influences price negotiations in the U.S. The report was based on information gathered from patients and their families, representatives from SMA patient advocacy groups, clinicians, researchers, insurers, and the manufacturers of the two medicines. Nevertheless, ICER noted that their comparative analysis was limited by several factors, including the limited number (to date) of patients treated with Zolgensma, narrow trial eligibility criteria, age differences at treatment initiation, and limited long-term data. Further data on the effects of both therapies may help to better assess their cost-effectiveness.

No. 1 — “FDA Approves Zolgensma, 1st Gene Therapy to Treat SMA in Children Up to Age 2

Our most-read article of 2019 concerned the approval of Novartis’ Zolgensma by the U.S. Food and Drug Administration (FDA) for the treatment of all types of SMA in infants and children under 2 years. With this approval, Zolgensma became SMA’s first gene therapy and second disease-modifying treatment. The FDA’s decision was based mainly on data from the pivotal Phase 1 START trial (NCT02122952) and its long-term extension study evaluating Zolgensma in SMA type 1 babies. Results highlighted that two years after a single Zolgensma administration, the now-toddlers showed survival and motor function improvements in striking contrast to SMA’s natural history.  “We believe Zolgensma could create a lifetime of possibilities for the children and families impacted by this devastating condition,” said Vas Narasimhan, Novartis’ CEO.


At SMA News Today we hope these stories and our reporting throughout 2020 help to better inform and improve the lives of everyone affected by SMA.

We wish all our readers a happy 2020.