Top 10 SMA Stories of 2018

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by José Lopes, PhD |

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SMA, top 10, 2018

SMA News Today brought you daily coverage of important findings, key treatment developments and clinical trials related to spinal muscular atrophy (SMA) throughout 2018.

We look forward to reporting more news that is important for the SMA community during 2019.

Here are the top 10 most-read SMA articles of 2018, with a brief description of what made them relevant and interesting for patients, family members and caregivers.

No. 10 — “Possible $4M Price for AVXS-101, ‘Foundational’ SMA Gene Therapy, Could Be Cost-Effective, Novartis Says”

The latest advancements related to Novartis’ gene therapy Zolgensma (onasemnogene abeparvovec-xxxx) — previously called AVXS-101 — received substantial attention from our readers. If approved, Zolgensma will become the first gene therapy for SMA patients and their second disease-modifying treatment after Spinraza (nusinersen).

What other stories from last year are you still thinking about? Share the link(s) in our forums.

In November, the company presented its R&D and Investor update, in which it discussed a possible $4 million to $5 million price tag for its “one-time, potentially curative” treatment for SMA. David Lennon, PhD, president at Novartis-owned AveXis, which originally developed Zolgensma, said the company believes that price would be cost-effective. Its calculations were based on the price of Biogen’s Spinraza (the first approved SMA treatment), which amounts to about $4.1 million per patient over 10 years. The company also addressed how it plans to ensure rapid access for all patients.

No. 9 — “ICER to Compare Clinical Efficacy and Value of Spinraza and AVXS-101 in Treating SMA”

In August, the Institute for Clinical and Economic Review (ICER), a nonprofit analysis group, announced it would compare the clinical effectiveness and value of Spinraza with that of Zolgensma. It included an “open input” period for anyone interested, while also intending to gather opinions from key patient and advocacy groups, as well as clinical specialists. The report will be reviewed at a March 2019 meeting of the New England Comparative Effectiveness Public Advisory Council.

No. 8 — “AveXis Asking FDA, EU to Approve AVXS-101 as 1st Gene Therapy for SMA Type 1″

In October, AveXis filed requests for the approval of Zolgensma to treat infants with SMA type 1 with regulatory authorities in the U.S., E.U., and Japan. The requests apply to type 1 infants up to 9 months treated via intravenous (IV) delivery. Further requests for other SMA types and older patients are anticipated. The U.S. Food and Drug Administration (FDA) later decided to grant priority review to this application, largely based on a Phase 1 clinical trial (NCT02122952) showing that all 15 treated infants survived and maintained motor function benefits at 24 months post-treatment. Decisions by all three agencies are expected by mid-2019. Zolgensma uses a genetically engineered virus to deliver a functional copy of the SMN1 gene to motor neurons. This gene is mutated in SMA patients, preventing the production of functional SMN protein. AveXis president, David Lennon, said Zolgensma “addresses the genetic root cause of SMA without the need for repeat dosing.”

No. 7 — “FDA Lets AveXis Know the Information It Needs to Possibly Approve AVXS-101 for SMA Type 1″

At the start of the year, the FDA told AveXis the information it needed to consider approving Zolgensma for the treatment of patients with SMA type 1. Company officials and regulators discussed the results of the initial Phase 1 trial. AveXis also was planning to present findings from its Phase 3 STR1VE trial (NCT03306277) in a pre-Biologics License Application meeting with the FDA scheduled for the second quarter of the year. STR1VE has shown improved movement ability, as well as no need for respiratory or nutritional support in children younger than 6 months who were treated with Zolgensma.

No. 6 — “Infant Motor Function Improves With Longer Spinraza Treatment, New Analysis Reports”

Data from three long-term studies have added to the body of evidence showing Spinraza’s overall benefit for patients.  The clinical trials — Phase 3 ENDEAR (NCT02193074) in infants with infantile-onset SMA, Phase 2 NURTURE in asymptomatic newborns (NCT02386553), and Phase 3 CHERISH in children with late-onset SMA (NCT02292537) — reported a correlation between the duration of SMA treatment with Spinraza and motor and strength benefits in infants. These patients also were likely to be hospitalized for respiratory complications and those who spent less time in the hospital. The results also showed that treatment with Spinraza prior to or quickly after symptoms begin is more likely to lead to greater improvement. “This is a broad benefit … clearly beyond what’s expected in the natural history” of SMA progression, said Wildon Farwell, Biogen‘s senior medical director of clinical development.

No. 5 — “AveXis Gene Therapy Used in Series of SMA Clinical Trials Both Safe and ‘Transformative,’ Executives Say in Interview”

In February, we published two articles from an interview with Sukumar Nagendran, then chief medical officer at AveXis, and Brian Kaspar, the company’s chief scientific officer. The first article covered specificities of the viral capsule used in Zolgensma and how they differ from a vector that also delivers a fully-functional human SMN1 gene and has been reported to cause severe liver and motor neuron toxicity in monkeys and piglets. By February, the effectiveness and safety of the vector used in Zolgensma — AAV9 — had been studied for years in various animal models and in 18 children, without relevant safety issues being raised. “[S]ome of the children have been on the therapy for nearly four years,” Kaspar said. Overall, considering preclinical and clinical data AveXis already had, Zolgensma continued to show “transformative impact,”  Nagendran said.

No. 4 — “First Patient Dosed in Phase 3 Trial of AVXS-101 in Presymptomatic Infants with SMA Types 1, 2 and 3″

In April, we reported the dosing of the first patient in the open-label SPR1NT Phase 3 (NCT03505099) trial, intended to test intravenous-delivery of Zolgensma in presymptomatic infants with SMA types 1, 2 and 3. Patient recruitment is still ongoing for a planned total of 44 babies younger than 6 weeks. Participants with different copy numbers of the SMN2 gene — able to produce the SMN protein, but in an unstable and shorter-than-normal form — will be assessed separately for the achievement of key developmental milestones, since the more copies a patient has, the less severe the disease.

No. 3 — “New Method of Spinraza Delivery May Give More SMA Patients Access to Therapy, Study Reports”

Spinraza is currently delivered via intrathecal injection — meaning it is injected into the spinal canal — every four months throughout a patient’s life. As such, it may present challenges for patients with spine deformities, along with other complications, particularly in newborns and young children. To overcome these issues, scientists have developed a new experimental method of delivery, using a catheter inserted in the spinal cord that is connected to an implantable self-sealing silicone disk under the skin. This disk can be punctured with a special needle to administer the treatment. Tests in 10 SMA patients with advanced disease and spine deformities showed good safety and tolerability results. Also, this method could reduce the cost of Spinraza administration by five to 10 times.

No. 2  “AVXS-101 Sets Out to Show It Might Be ‘Transformative’ for All SMA Types: Interview with AveXis”

Our second February article on an interview with AveXis covered the company’s broad range of clinical trials on Zolgensma — including the STRONG Phase 1 study (NCT03381729) in type 2 children (still recruiting participants) and the planned REACH trial in types 1-3 patients up to 18 years and not eligible for the other studies. The story also highlighted how the therapy was developed and AveXis’ push for newborn screening of SMA at U.S. federal and state levels. In July, Alex Azar, U.S. Secretary of Health and Human Services (HHS), added SMA to the Recommended Uniform Screening Panel (RUSP) for newborns, with seven states already adopting the recommendation.

No. 1 – “Researchers Discover Promising New Gene Therapy Approach for Spinal Muscular Atrophy”

Our most read article of 2018 described a potential gene therapy for SMA. Chinese researchers generated induced pluripotent stem cells (iPSCs) — able to differentiate into almost all types of cells in the body — from urine cells collected from a 22-year-old man with SMA type 3 and from a healthy study participant. The team then used the CRISPR/Cpf1 gene editing system to modify a single nucleotide — the basic unit of DNA — in the SMN2 gene and convert it to a SMN1-like gene. The approach led to the production of full-length and functional SMN protein in both the iPSCs and in their derived motor nerve cells. The team said this strategy “may provide a universal gene therapeutic approach for most SMA patients.”


At SMA News Today we hope these stories and our reporting throughout 2019 contribute to informing and improving the lives of everyone affected by the disease.

We wish all our readers a happy and inspiring 2019.