Spinal Muscular Atrophy (SMA) is a rare genetic, progressive, disorder that affects the control of muscle movement. Caused by the loss of motor neurons in both the brainstem and the spinal cord, SMA leads to muscle atrophy and results in severe symptoms in patients, such as loss of walking ability, the ability to sit up, and controlling head movements. Patients battling SMA may also suffer from breathing complications and lose the ability to swallow.
There are many types of SMA, typically distinguished by the age when symptoms begin and severity of muscular weakness.
Infants with Type I SMA show severe muscular weakness in the first few months of life, cannot sit without assistance, and cannot support their head. Infants will usually lose almost all movement before age 1, and without proper respiratory care, most will pass away before age 2. Patients with Type II SMA can sit without assistance but cannot walk or stand unaided. They will almost never walk and experience breathing and respiratory issues. SMA II is usually diagnosed in infants between 6 and 12 months of age. Type III SMA occurs a bit later in life, developing between early childhood and adolescence. Individuals impacted by SMA III will have difficulty walking and climbing stairs. Patients Type IV SMA traditionally show symptoms after the age of 30. Symptoms may include muscle weakness and breathing difficulties.
SMA is caused by mutations in the SMN1 and other genes. The SMN1 and SMN2 genes are responsible for creation of a protein called survival motor neuron (SMN), which are located in the brainstem and the spinal cord, and control muscle movement.
The SMN1 protein is responsible for the bulk of SMN development. While SMN2 creates small amounts of SMN, the production amount is not enough to allow for normal function if the SMN1 gene is damaged and/or not working. Some patients with Type II, III, or IV have multiple copies of the SMN2 gene, which can help lessen the severity of SMA because they help replace SMN protein missing due to the defective SMN1 gene.
Without SMN, or with only small amounts present, in the brainstem and spinal cord, motor neurons die. This leads to muscle weakness and waste along with a number of complications that vary in severity for patients, most of which are life-altering and life-threatening.
Genetic Condition Caused By SMN1 Gene Mutation
Damage or deficient SMN1 leads to a lack of SMN protein in the brainstem and spinal cord. SMN is responsible for motor neuron development, which control muscle movement.
Lack of Enough SMN Leads To Progressive Symptoms
The lack of SMN leaves patients suffering from a host of life-altering and life-threatening symptoms. These symptoms vary in severity, depending on how much SMN protein patients have to create motor neurons. Symptoms can include the inability to sit, stand, or walk, developmental delay, breathing difficulties, and swallowing difficulties.
There are many symptoms and associated consequences for patients suffering from SMA, and the severity of these symptoms varies depending on the amount of SMN the body is able to produce. The type of SMA that a patient gets diagnosed with depends on when symptoms were first prevalent, coupled with the severity of symptoms.
Until recently, management of symptoms was the only course of care for patients. In 2016, the first ever treatment for SMA was approved by the FDA and the European Commission. It was approved for use in Canada by Health Canada in 2017. More information on this treatment can be found in our TREATMENT section.
Patients with both SMA I and II experience muscle fasciculations, or involuntary twitching of the muscles. Infants with SMA I experience this on the tongue as well.
Children suffering from Type I and II SMA experience decreased or absent deep tendon reflexes, such as the ones that occur when you tap on the knee, elbow, or wrist.
Children suffering from SMA I and II develop numerous respiratory problems. Respiratory infections such as pneumonia are common. Patients battling SMA III rarely experience respiratory complications.
Diminished Muscle Tone
Patients with severe SMA suffer from hypotonia, or diminished muscle tone. Patients with SMA I develop symptoms of hyoptonia in the first few months of life, while patients with SMA II see this symptom become prevalent between 6-12 months of age.
Muscle weakness prevents children with SMA I from being able to sit up, support their head, or walk. Patients with SMA II have difficulty standing and walking, and often require a wheelchair very early in life. Muscle weakness also leads to swallowing problems for both Type I and some Type II patients. Children with SMA III may not walk or stand on their own, while others do.
Severely Shortened Lifespan
Sadly, without treatment for SMA, the lifespan of patients is severely shortened, especially for patients diagnosed with the most severe forms of the disease. It is imperative that patients receive access to life-sustaining treatment as soon as possible after diagnosis to help slow down or halt progress of life-threatening symptoms.
In 2016, the first ever treatment for SMA was approved in the US and European Union. Spinraza, created by Biogen Pharmaceuticals, provides patients with a synthetic version of the SMN proteins their bodies are lacking. This treatment was passed through the approval process in both the US and Europe because of the tremendous unmet need the treatment addressed in patients. Spinraza was given Health Canada approval in mid-2017.
Clinical trial results were very promising, with patients seeing “clinically meaningful improvement in motor function compared to untreated individuals.” Studies have shown that Spinraza will be beneficial to all types of patients battling SMA.
Reimbursement of Treatments for Rare Diseases in Canada – A Long and Arduous Process
From an access standpoint, there is no reason for delay, and no reason why patients who need access can’t receive it soon after regulatory approval from Health Canada. Patients suffering from these rare and progressive diseases don’t have the luxury of time on their side, and the current process is long and arduous. Biogen can and should help patients now while these processes play out, and I remain hopeful that they will for all types of SMA. Andrew McFadyen, Executive Director, The Isaac Foundation
Unfortunately, any approval by Health Canada for treatments for a Rare Disease doesn’t mean that patients can begin receiving therapy immediately. Canada’s lack of an Orphan Drug Plan, coupled with the bureaucratic approval process that differs in individual provinces, often leaves patients lacking the treatment they desperately need. The reason? While Health Canada may approve a treatment for use, it’s still up to individual provinces to decide whether they will pay for the treatment or not. The process to decide whether to cover such treatments is long and arduous, beginning with a review by CADTH (Canadian Agency for Drugs and Technology in Health). This review can take 6-12 months, at which point a recommendation will be rendered to either list the drug on provincial drug plans, list the drug with conditions (such as a decrease in price from the manufacturer or restrictions on which portion of the patient population can access the drug), or do not list at all.
If a drug receives a positive recommendation, the file then moves to the pCPA (Pan-Canadian Pharmaceutical Alliance) for bulk pricing negotiations. In this stage, negotiators assigned to represent all prices open discussions with the company in an attempt to come to terms on the cost. Because rare disease drugs are often some of the most expensive in the world, these negotiations take a very long time – anywhere from 6-18 months. If negotiations result in a deal, provinces can then decide to accept the deal and begin delivering the drug to patients on their drug plan. Occasionally, no deal is able to be struck between pCPA and the company, and the drug remains difficult or impossible to secure for patients in need.
While these processes undergo their reviews, Physicians with patients suffering from a rare disease may fill out a request for reimbursement application and submit it to the provincial Ministry of Health. From there, the application is reviewed and a decision to cover the cost of treatment is either approved or, in most cases, denied. Most reasons governments provide for denial are due to a lack of evidence of the benefits these treatments provide patients, especially while the CADTH reviews are in place. In many provinces, policies are in place that prevent these decisions from being rendered until the above reviews have been completed. Companies can work directly with governments to see how drugs can be accessed while reviews are taking place, and they are often encouraged to show a willingness to help provide access for their patient population by drugs on a compassionate use basis.
In Canada, Biogen has agreed to provide drug to patients battling SMA Type I only (approx. 30 patients in Canada out of an estimated 700 total SMA patients). The Isaac Foundation has made numerous proposals to the company in an effort to open slots for patients in dire need who are suffering from Type 2 and 3 as well. We will continue these efforts and post any updates on our website if and when they are available.
Bureaucratic Path to Reimbursement – Information and Estimated Timelines
Bureaucratic Path to Reimbursement Could Take 18-24 Months Longer
Biogen submits SPINRAZA to Health Canada for review and approval for use in Canada. The review was considered a “priority” review because of the potential impact the therapy could have on patients. Submission took place in December of early 2017, and approved by Health Canada in June of 2017.
STEP 2 - Submission and Review to the Common Drug Review (CDR)
The Common Drug Review is a “process for conducting objective, rigorous reviews of the clinical, cost-effectiveness, and patient evidence for drugs.” The CDR completes their review and recommends to provinces whether a drug should be reimbursed or not. Submission to CADTH for CDR review took place in late June, 2017. A decision could be rendered at the end of 2017.
STEP 3 - Negotiations Begin With the Pan-Canadian Pricing Alliance (pCPA)
The Pan-Canadian Pricing Alliance works to capitalize “on the combined ‘buying power’ of drug plans across multiple provinces and territories” to bring the cost of expensive treatments down. If SPINRAZA receives a recommendation at CDR to continue to the pCPA negotiation process, negotiations could take 12-18 months.
Months for Health Canada Review(Approval: June, 2017)
Months Estimated to CADTH process (Application Submitted: June, 2017)
Months Estimated to Negotiate Price through pCPA (Submission: After CDR is completed)
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