News

Parents and caregivers of patients with spinal muscular atrophy (SMA) take great interest in orphan drug development, soaring healthcare costs, patient assistance programs and controversial “right-to-try” legislation — all issues on the agenda during the upcoming Rare Disease & Orphan Products Breakthrough Summit. “One of the chief challenges of 21st-century…

Spinraza (nusinersen) may provide more benefits to infants with spinal muscular atrophy (SMA) if the treatment is started early, Biogen reported during presentations at the ongoing 22nd International Congress of the World Muscle Society in St. Malo, France. But the treatment can also provide benefits to SMA patients…

Preliminary data from the Phase 2 SUNFISH trial show PTC Therapeutics' investigative drug RG 7916 increases production of the SMN (survival motor neuron) protein in types 2 and 3 spinal muscular atrophy patients. The results were presented by PTC Therapeutics at the 22nd International World Muscle Society (WMS) Congress in St. Malo, France, Oct. 3-7. Part 1 of the study assessed the safety, tolerability, effectiveness, and pharmacological profile of several doses of orally administered RG 7916 in both ambulatory and non-ambulatory SMA patients. Part 2 will include 150 non-ambulatory patients to determine the safety and effectiveness of the recommended dosage of RG 7916 selected from Part 1. An open-label extension study will follow. The development and production of RG7916 is part of a joint effort between PTC Therapeutics, Swiss multinational Roche, and the SMA Foundation. Earlier this year, RG7916 was granted orphan drug and fast track designation by the FDA for the treatment of patients with SMA. PTC Therapeutics created an SMA research program in 2006 in partnership with the SMA Foundation to pursue a therapy for the devastating disease. In November 2011, Roche obtained an exclusive worldwide license to the PTC/SMA Foundation program studying alternative splicing (synthesis of different protein variants from the same messenger RNA sequence) of the SMN2 gene.

The gene therapy developer AveXis will start a pivotal clinical trial of AVXS-101 for people with SMA type 1. U.S. Food and Drug Administration officials agreed to the trial after AveXis submitted information the agency requested on the drug's manufacturing process and other matters. The request was made at a meeting the sides held in May. AveXis did not say in its announcement whether the pivotal trial would be a Phase 2 or Phase 3 study. The company has completed a Phase 1 trial of AVXS-101. Most pivotal trials are Phase 3, but occasionally they can be Phase 2. . AVXS-101 is a proprietary gene therapy for SMA types 1 and 2. Designed to deliver a functional copy of an SMN gene to motor neuron cells, it aims to prevent additional muscle degeneration. The pivotal trial in SMA type 1 – called STR1VE – will be an open-label, single-arm, single-dose, multi-center study. It will evaluate the safety and effectiveness of a one-time dose of AVXS-101 delivered intravenously or directly into the blood circulation. Researchers will administer a dose established in a Phase 1 trial that they confirmed with new analytical methods that the FDA reviewed. The dose was also extensively tested in a mouse model of SMA. AveXis expects to enroll in the trial at least 15 patients with SMA Type 1 younger than six months of age. One of the trial's primary objectives will be to see if AVXS-101 can help an 18-month-old infant sit without help for at least 30 seconds. Another primary objective will be to help an infant achieve event-free survival at 14 months of age, and to see whether AVXS-101 helps patients thrive — that is,  not requiring feeding support, tolerate thin liquids and maintain weight. Another secondary objective will be to help infants get off ventilator support at 18 months of age. Updates of these studies are expected at the end of the year.

Novartis will resume clinical development of branaplam to treat spinal muscular atrophy after a two-year pause brought on by safety concerns, the Swiss company announced in a letter published by Cure SMA. The ongoing clinical trial will start enrolling patients as soon as the research team obtains approvals by health authorities and the ethics committee. The study recruits infants younger than six months with type 1 SMA. All will receive branaplam, the name Novartis chose for its compound when reopening clinical investigations. While the study originally only included four European study centers — in Belgium, Germany, Denmark and Italy — Novartis said it plans to add more sites including some in the United States, following a green light from the U.S. Food and Drug Administration (FDA). The branaplam clinical trial halted new enrollments in May 2016 after simultaneous animal studies linked branaplam to unexpected nerve damage and other injuries. Infants already enrolled continued treatment and have been closely monitored. Novartis has worked with outside experts to understand the meaning of the animal findings. The fact that enrollment has resumed signals that Novartis — which has not commented on its relevance — no longer perceives the animal data as an immediate patient hazard. Besides resuming recruitment, the company has modified its trial design after considering feedback from the babies’ parents and study investigators. For instance, infants can now receive their weekly dose of branaplam orally, instead of via a feeding tube, which was the only option when the trial started. The company also added nerve tests to the trial as an additional safety procedure. As clinical development of branaplam continues, Novartis is also working with regulators to expand drug testing to include patients with other types of SMA.

Biotech company Scholar Rock has Secured a key U.S. Patent for a Potential SMA Therapy that targets Myostatin The U.S. Patent and Trademark Office has issued a patent for antibodies that selectively bind and inhibit myostatin – a protein that naturally prevents muscle mass growth. This new patent granted to Scholar Rock will protect its drug candidate, SRK-015, which the Cambridge, Massachusetts company is developing to improve muscle strength and motor function in patients with spinal muscular atrophy and other motor disorders. Previous studies have showed that people with mutated myostatin genes also have significantly larger muscle mass. This suggests that inhibiting myostatin's activity could potentially treat several motor illnesses, including SMA. Preclinical testing in non-human primates has shown SRK-015’s potential to improve muscle cell function and strength. Animals given SRK-015 improved lean muscle mass as well as the function of some specific muscle fibers that are often simpaired in many SMA patients. Scholar Rock is working to take its lead candidate for treatment of SMA into clinical trials. The company plans to evaluate SRK-015's safety and effectiveness in combination with other therapies designed to correct the genetic defects that lead to SMA. By mid-2018, Scholar Rock also intends to address SRK-015's potential as a standalone therapy in patients with certain subtypes of the rare genetic disorder. The recently issued patent will provide broad protection for SRK-015 and other therapeutic antibodies that use the same mechanism of action. These antibodies can be explored as therapeutic strategies for several neuromuscular and other diseases.

This year's Boston Rare Disease Film Festival will Feature an SMA Documentary Gareth Burghes' documentary, Life & Atrophy, which runs 24 minutes, will be part of Disorder: The Rare Disease Film Festival — a first-of-its-kind event in Boston this early October. The festival covers more than two dozen rare diseases. The 30 films, which will be shown in seven screenings, range in length from one to 65 minutes. Life & Atrophy is billed as “a documentary following one family’s story to defy genetic fate.” Burghes said the idea for his movie stemmed from his geneticist father's involvement in  clinical trials of SMA patients. It tells the story of Miles McIntosh, a 5-year-old boy with SMA type 2, as his parents, Nikki and Tony McIntosh, sign him up for a trial to test the recently FDA-approved therapy Spinraza. Burghes said that SMA “has gone from an orphan disease with nearly nothing known about it, to now having its first FDA-approved drug on the market, as well as other treatments in the pipeline. The film represents what can be accomplished when families, researchers, and pharmaceutical companies join together to solve complex diseases.” The Boston film festival is the brainchild of two fathers --Daniel DeFabio, whose son has Menkes disease, a rare disorder that affects only one in 100,000 newborns -- and Bo Bigelow, who's daughter Tess has a genetic disease that’s even more rare. Only 23 people worldwide have it; there isn’t even a name to describe her illness. The Rare Disease Film Festival runs Oct. 2-3 in Boston. The SMA documentary Life & Atrophy will air at 2:30 p.m. on Oct. 2nd .

Cure SMA will host a webinar on spinal muscular atrophy (SMA) today at 1 p.m. EST. The event focuses on access to Spinraza — the only U.S. government-approved therapy to treat the disease, CureSMA said in a press release. Topics to be covered include the current status of dosing in individual…

Ionis Pharmaceuticals has received $40 million in milestone earnings from Biogen following Japanese regulatory approval of the price of  Spinraza, Biogen's treatment for spinal muscular atrophy. So far, Ionis has earned more than $435 million from Biogen in Spinraza-related regulatory approvals and sales royalties, it said in a press release. The market performance speaks to the overwhelming success that the drug is having in treating the SMA patient population. Spinraza has been approved by U.S, European, Canadian, Brazilian and now Japanese regulatory agencies. Ionis is now working to bring the treatment to other countries including Switzerland, Israel, South Korea and Australia, where it is now under review by regulatory agencies Biogen licensed global development, manufacturing and commercialization rights to Spinraza from Ionis in August 2016. In so doing, it assumed responsibility for all activities and costs associated with the drug. Ionis is eligible to receive tiered royalties on Spinraza sales up to a percentage in the mid-teens, in addition to up to $150 million in milestone payments based on regulatory approvals. Spinraza became the first approved SMA treatment in December 2016, when the U.S. Food and Drug Administration supported its use in children and adults. The FDA made that decision within three months of Biogen's regulatory filing. Biogen sponsors one of the largest Expanded Access Programs worldwide, offering Spinraza free of charge to patients requesting it in countries that have not yet approved its use. About 600 children with infantile-onset SMA in 24 countries began treatment under such programs, the release said.

Today is thursday, September 14. I'm Mike Nace, Executive Editor of SMA News today A cocktail of two microRNAs and two transcription factors is enough to transform human skin cells directly into motor neurons, scientists report — an achievement of potentially considerable importance in understanding such motor neuron diseases as spinal muscular atrophy. Damage to motor neurons underlies several devastating and paralyzing diseases, from SMA to ALS. Scientists have struggled to grow human motor neurons in the lab for research purposes, which is one reason this work is so notable. Researchers were able to convert skin cells from healthy adults into motor neurons. Importantly, this process also didn’t require skin cells to change into stem cells before becoming motor nerve cells. In the current study, the research team further investigated the role of these microRNAs and how they help convert skin cells into motor neurons. It found that the microRNAs identified in the study assist cells in holding at a stage where they are ready to convert to neurons. But they were inactive and need more help. After extensive research, researchers identified two transcription factors — ISL1 and LHX3 — were the missing link. Once added to the mix, skin cells turned into spinal cord motor neurons in about 30 days. The four factors — microRNA-9, microRNA-124, ISL1 and LHX3 — help cells shed their skin cell “genetic identity” and embrace instructions that lead them to becoming motor nerve cells, scientists said. The converted motor neurons showed a similar genetic profile — in terms of gene activation and how they work — to mouse motor neurons. How well their genetic profile compares to human motor neurons is still a question, because these cells are very difficult to obtain from living adults. Future studies will let researchers determine how well their converted motor neurons match natural human motor neurons.