FAQs About Evrysdi (Risdiplam)

Evrysdi (risdiplam) is an oral liquid treatment approved in the U.S. for infants through adults with spinal muscular atrophy (SMA) — patients age 2 months and older with any disease type. Roche and Genentech developed Evrysdi in collaboration with PTC Therapeutics and the SMA Foundation.

Here are answers to some questions you might have about this therapy.

What is Evrysdi, and how does it work?

Evrysdi, a daily treatment, works by addressing the underlying cause of SMA: a mutation in the SMN1 gene that results in low amounts of the SMN protein. This protein is essential for the survival of motor neurons, or nerve cells that control muscle movement, including those we use to breathe. SMN might also be of importance to other tissues, like bone, and organs like the liver, heart, and pancreas.

Humans, unlike other mammals, have a backup gene called SMN2 that also carries the instructions necessary for cells to make SMN protein. Due to an event called alternative splicing, however, cells can only make between 10% and 15% of properly working SMN protein from this second gene. This is why patients with more than one or two SMN2 gene copies typically have less severe disease.

Alternative splicing is important for protein synthesis, as it allows a gene to give rise to multiple proteins by adding or removing pieces of genetic material called exons. Genes take or leave exons much like a cook chooses among ingredients in adapting a recipe. In SMN2, this splicing event removes exon 7, making the SMN protein the backup gene encodes for unstable.

Evrysdi, in ways similar to the first approved disease-modifying treatment for SMA, Spinraza (nusinersen) by Biogen, works by modifying SMN2 splicing. Specifically, it prevents exon 7 from being removed, allowing for greater synthesis of a full-length and functional SMN protein. This could increase the survival of motor neurons. 

Motor neurons are not regenerating cells, unlike muscle or blood cells that renew themselves regularly. “Once you’re born with them — as the dogma is — that’s what you have,” Karen Chen, a neuroscientist and CEO of the SMA Foundation, said in an interview with SMA News Today.

How do I take Evrysdi?

Both children and adults can either swallow Evrysdi or take it through a gastronomy tube (feeding tube) each day, after a meal, using the provided oral syringe. Patients and caregivers are advised to not let the medicine sit in the syringe, but to administer it within five minutes of preparing a dose.  

Evrysdi’s dose is set based on a patient’s age and body weight, with the optimal therapeutic dose set at 0.2 mg/kg for children under 2 years old, 0.25 mg/kg for those 2 years and older weighing less than 44 lbs (20 kg), and 5 mg for patients 2 and older weighing 44 lbs or more, according to the FDA’s prescribing label.

Your doctor might recommend that you take Evrysdi each morning, after breakfast. Researchers don’t think that the time of day you choose to take this medicine is of central importance. However, it is extremely important that, once you’ve chosen when you will take Evrysdi or give it to a child, you do so around the same time each day. Mornings are usually best for remembering an essential daily treatment.

The FDA recommends drinking a glass of water after taking Evrysdi, to ensure all the medicine is swallowed. If a feeding tube is used, flush the tube with water after treatment administration.

What if I or my child misses a dose?

If you or your child misses a dose, and you are within six hours of the missed dose, take the prescribed dose as soon as possible.  Then resume your regular dosing schedule the next day.

If you are beyond six hours from your set dosing time, skip the missed treatment and resume your normal dosing schedule on the next day. If a child does not take the entire dose at one sitting, or you or a patient vomits after taking a dose, do not  try to administer more of the medicine. Wait until the next day, and the next regularly scheduled dose.

Where do I go to get Evrysdi?

A perceived advantage with Evrysdi is that once you get a prescription for it, you likely won’t need to go anywhere to be given it. As a liquid that most patients will swallow each day, it’s easy to take it at home.

According to Roche, Evrysdi can be directly shipped to patients’ places of residence through Accredo Health Group, an Express Scripts specialty pharmacy.

How much does it cost?

Evrysdi’s carries a maximum list price of $340,000 a year, according to Genentech, the company marketing this treatment. That price comes into effect when a patient’s weight reaches 44 lbs (20 kg), which is usually around age 6.

Pricing is based on weight for patients weighing less than 44 lbs, and rises with increasing weight until it reaches its maximum list price. For 2-year-olds weighing about 15 lbs (6.8 kg), Evrysdi’s yearly cost is estimated at less than $100,000.

Can I switch treatments?

Researchers are still investigating the safety and efficacy of switching from Spinraza to Evrysdi, or the reverse — or of using Spinraza or Evrysdi after or before getting a single dose of Zolgensma, the one-time gene therapy for SMA by Novartis.

An open-label and fully enrolled Phase 2 clinical trial called JEWELFISH (NCT03032172) is evaluating the safety, tolerability, pharmacokinetics (movement in the body), and pharmacodynamics (effect on the body) of Evrysdi in SMA type 1, 2, and 3 patients, ages 6 months to 60 years, who previously were treated with Spinraza, Zolgensma, or olesoxime.

Early results indicate both safety — including no treatment-related side effects causing withdrawals from the trial — and potential added benefit as reported by researchers in June 2020.

Are patient assistance programs in place?

Genentech is running an online patient assistance program, called MySMA Support, for people in the U.S. with a prescription for Evrysdi. Trained staff with this program will be able to answer questions about the treatment and its use. They will also be able to provide educational information, and help families in understanding insurance coverage or navigating financial assistance options.

Patients needing information can also go online at Evrysdi.com, or call 1-833-EVRYSDI (833-387-9734).

What if I live outside the U.S.?

Risdiplam, as Evrysdi is known by its investigative compound name, is currently under review by regulatory agencies in seven countries: Brazil, Chile, China, Indonesia, Russia, South Korea, and Taiwan.

A filing is expected to be made shortly to the European Medicines Agency (EMA), the regulatory agency for the European Union. The EMA has given risdiplam orphan and priority medicines (PRIME) designations; both assure regulatory support, but PRIME also carries the possibility of an accelerated review.

Roche also announced the opening of a compassionate use program (CUP) for type 1 SMA patients in the EU, England, and elsewhere, wanting and eligible for access to risdiplam before its approval in their home country. This program, which opened in early 2020, was expanded at mid-year to include type 2 patients whose  Spinraza (nusinersen, by Biogen), treatment is being interrupted by the COVID-19 pandemic.

This pre-approval compassion use program, Roche said in an email answer to SMA News Today, is “available in countries that have the capacity and capability to safely prescribe, dispense and monitor the use of risdiplam and for patients who meet the eligibility criteria.” Treating physicians are generally expected to file risdiplam CUP requests.

Last updated: Aug. 8, 2020

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SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.