| Coverage Policy Manual | |
| Policy #: | 2019011 |
| Category: | Pharmacy |
| Initiated: | November 2019 |
| Last Review: | September 2025 |
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| Treatment for Spinal Muscular Atrophy | |
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| Description: |
Spinal muscular atrophy (SMA) is an inherited disorder caused by homozygous deletions or variants in the
SMN1 gene in chromosome 5. This gene is responsible for producing the “survival of motor neuron” protein (SMN1). Because of absent or low levels of survival motor neuron 1 protein, the motor neurons in spinal cord degenerate, resulting in atrophy of the voluntary muscles of the limbs and trunk. During early development, these muscles are necessary for crawling, walking, sitting up, and head control. The more severe types of SMA can also affect muscles involved in feeding, swallowing, and breathing. Treatments include:
The exact role of the SMN protein in motoneurons has not been completely elucidated and levels of the SMN protein required for optimal functioning are unknown (Wang, 2007).
SMN2 is a nearly identical modifying gene capable of producing nearly identical compensatory SMN2 protein. However, 70% to 90% of the transcripts produced from the
SMN2 gene produce a truncated protein that is defective and unstable due to lack of exon 7 (Lorson, 1999). Further, humans exhibit variability (range, 0-6) in the number of copies of the
SMN2 gene and copy number is inversely proportional to severity of disease (Lefebvre, 1997). These factors in tandem lead to wide variability in disease severity.
SMA is classified into 4 main categories (with additional subcategories) based on the age at the onset of symptoms (Muscular Dystrophy Association, 2017; National Organization for Rare Disorders, 2012). Generally, early onset of disease directly correlates to severity of symptom and rate of disease progression. There is no exact marker to classify these categories, and they are not well-distinguished by ICD-10-CM code.
The prevalence of SMA is estimated to be between 9.1 and 10 per 100,000 live births (Prior, 2010; Sugarman, 2012). In 95% cases, both copies of the SMN1 exon 7 are absent. The remaining 5% cases are compound heterozygotes for
SMN1 exon 7 deletion and small intragenic variants. The molecular diagnosis of SMA consists of the detection of the absence of exons 7 of the
SMN1 gene in the majority of cases (Prior, 2010).
Regulatory Status
On December 23, 2016, nusinersen (e.g., Spinraza; Biogen) was approved by the U.S. Food and Drug Administration (FDA) for treatment of pediatric and adult individuals with spinal muscular atrophy.
On May 24, 2019, onasemnogene abeparvovec-xioi (e.g., Zolgensma; Avexis) was approved by the U.S. Food and Drug Administration for treatment of pediatric individuals less than 2 years of age with spinal muscular atrophy with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
The FDA has issued a black-box warning for onasemnogene abeparvovec-xioi due to the risk of acute serious liver injury and elevated aminotransferases. Individuals with pre-existing liver impairment may be at higher risk.
On August 7, 2020 the FDA approved risdiplam (e.g., Evrysdi) to treat individuals 2 months and alder with SMA. This is the first oral drug to treat this disease.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
After November 14, 2025, please refer policy number 2025026 for onasemnogene abeparvovec-xioi (e.g., Zolgensma) and policy number 2025027 Risdiplam (e.g., Erysdi).
Effective April 01, 2018, Prior Approval is required for Nusinersen (e.g., Spinraza).
The use of these drugs requires documentation of direct physician (MD/DO) involvement in the ordering and evaluation as well as a signature in the medical records submitted for prior approval.
INITIAL AND CONTINUATION APPROVAL will be for duration of treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
Effective November 15, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
INITIAL APPROVAL:
Nusinersen (e.g., Spinraza) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment
of individuals with infantile onset (type I), type II or type III spinal muscular atrophy with a documented genetic diagnosis of spinal muscular atrophy:
Note: The concurrent use of nusinersen with onasemnogene abeparvovec-xioi and/or risdiplam is not covered (see statement of non-coverage below).
CONTINUATION OF THERAPY:
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
Nusinersen (e.g., Spinraza), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, Nusinersen (e.g., Spinraza), for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The concurrent use of Nusinersen (e.g., Spinraza) with onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of individuals with type 0 and IV spinal muscular atrophy or for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the concurrent use of Nusinersen (e.g., Spinraza) with onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of individuals with type 0 and IV spinal muscular atrophy or for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
DOSING AND ADMINISTRATION
The prescribed regimen must be within the U.S. Food and Drug Administration dosing of 12 mg (5 mL) administered intrathecally per treatment; the first 3 loading doses should be administered at 14-day intervals. The fourth loading dose should be administered 30 days after the third dose. A maintenance dose should be administered once every 4 months thereafter.
Nusinersen (e.g., Spinraza) is available as 12 mg/5 mL (2.4 mg/mL) in a single-dose vial.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Effective October 4, 2023 to November 14, 2025
NUSINERSEN
Effective April 01, 2018, Prior Approval is required for nusinersen.
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
INITIAL APPROVAL STANDARD REVIEW for up to 6 months
The use of Nusinersen meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment
of individuals with infantile onset (type I), type II or type III spinal muscular atrophy with a documented genetic diagnosis of spinal muscular atrophy.
Note: The concurrent use of nusinersen with onasemnogene abeparvovec-xioi and/or risdiplam is not covered (see statement of non-coverage below).
CONTINUED APPROVAL (approval for 6 months or 1 year)
Incremental reauthorization for nusinersen for up to 1 year may be considered if the following conditions are met (UTD, Bodamer 2021):
Dosing and Administration
Dosing per FDA Guidelines
The prescribed regimen must be within the U.S. Food and Drug Administration dosing of 12 mg (5 mL) administered intrathecally per treatment; the first 3 loading doses should be administered at 14-day intervals. The fourth loading dose should be administered 30 days after the third dose. A maintenance dose should be administered once every 4 months thereafter.
Nusinersen is available as 12 mg/5 mL (2.4 mg/mL) in a single-dose vial.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Nusinersen, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, nusinersen, for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The concurrent use of nusinersen with onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of individuals with type 0 and IV spinal muscular atrophy or for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the concurrent use of nusinersen with onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of individuals with type 0 and IV spinal muscular atrophy or for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
ONASEMNOGENE ABEPARVOVEC-XIOI
Effective November 1, 2019, Prior Approval will be required for Onasemnogene Abeparvovec-XIOI (Zolgensma®).
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Onasemnogene abeparvovec-xioi meets member benefit certificate primary coverage criteria
that there be scientific evidence of effectiveness in improving health outcomes for the treatment
of individuals with infantile-onset or type I spinal muscular atrophy with a documented genetic diagnosis of spinal muscular atrophy.
Note: The repeat treatment or ante-partum use of onasemnogene abeparvovec-xioi is not covered (see statement of non-coverage below).
Note: Concurrent use of onasemnogene abeparvovec-xioi with nusinersen and/or risdiplam
is not covered (see statement of non-coverage below).
Dosing and Administration
Dosing per FDA Guidelines
The recommended dosage of onasemnogene abeparvovec-xioi is 1.1 × 10 to the 14th power vector genomes (vg) per kg of body weight. It should be administered as an intravenous infusion over 60 minutes. Systemic corticosteroids equivalent to oral prednisolone at 1 mg/kg should be administered according to the FDA approved prescribing label.
The FDA label states that "The safety and efficacy of Onasemnogene abeparvovec-xioi (e.g., ZOLGENSMA) in individuals with anti-AAV9 antibody titers above 1:50 have not been evaluated.” Baseline anti-AAV9 antibody testing is performed prior to infusion using. Retesting may be performed if anti-AAV9 antibody titers are reported as > 1:50.
Liver function (clinical exam, AST, ALT, total bilirubin, prothrombin time), platelet counts, and troponin-I levels should be monitored as per the prescribing label.
Where feasible, individual’s vaccination schedule should be adjusted to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec-xioi infusion.
Use of onasemnogene abeparvovec-xioi in premature neonates before reaching full term gestational age may not be recommended because concomitant treatment with corticosteroids may adversely affect neurological development.
Efficacy of onasemnogene abeparvovec-xioi in individuals with c.859G>C variant in SMN2 gene has not been evaluated.
Onasemnogene abeparvovec-xioi is available as a suspension for intravenous infusion, supplied as single-use vials.
Onasemnogene abeparvovec-xioi is provided in a kit containing 2 to 14 vials, as a combination of 2 vial fill volumes (either 5.5 mL or 8.3 mL). All vials have a nominal concentration of 2.0 x 10 to the 13th power vector genomes (vg) per mL. Each vial of onasemnogene abeparvovec-xioi contains an extractable volume of not less than either 5.5 mL or 8.3 mL.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications. It will be expected that this therapy will be administered through a certified treatment location. Please see:
http://www.curesma.org/zolgensma-administration-sites.html for locations of administration.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Onasemnogene abeparvovec-xioi, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes including but not limited to:
For those members without primary coverage criteria, onasemnogene abeparvovec-xioi, for any indication or circumstance not described above, including but not limited to the following is considered
investigational:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
RISDIPLAM
The FDA has deemed this drug to be appropriate for self-administration or administration by a caregiver (i.e., not a
healthcare professional). Therefore, the use of Risdiplam is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage. This policy applies to members whose plan utilizes AR BCBS pharmacy and has Risdiplam as a formulary option.
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
INITIAL APPROVAL STANDARD REVIEW is for 6 months.
Risdiplam meets member benefit certificate primary coverage criteria that there be scientific evidence for effectiveness in improving health outcomes for the treatment
of individuals type I, type II and type III SMA if ALL the following conditions are met:
Note: The concurrent use of risdiplam with onasemnogene abeparvovec-xioi and/or nusinersen is not covered (see statement of non-coverage below).
CONTINUED APPROVAL for 6 months or 1 year)
Incremental reauthorization for risdiplam for 1 year may be considered
medically necessary if the following conditions 1 and 2 are met:
Dosage and Administration
Dosing per FDA Guidelines
The prescribed regimen must be within the U.S. Food and Drug Administration guidelines. Risdiplam is dosed by age and body weight.
Age and body weight Daily Dosage
2 months to < 2 years of age 0.2 mg/kg
2 years and older weighing < 20 kg 0.25 mg/kg
2 years and older weighing > 20 kg 5 mg
Risdiplam is available as 60 mg as a powder for constitution to provide 0.75 mg/mL oral solution.
Risdiplam should be avoided in individuals with hepatic impairment.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Risdiplam, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes including but not limited to:
For those members without primary coverage criteria, the use of risdiplam for any indication or circumstance not described above, is considered
investigational including but not limited to:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective March 16, 2022 to October 3, 2023
I Nusinersen
Effective April 01, 2018, Prior Approval is required for nusinersen.
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of Nusinersen meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment
of patients with infantile onset (type I), type II or type III spinal muscular atrophy with a documented genetic diagnosis of spinal muscular atrophy
Initial approval is for 6 months
1. Diagnosis of spinal muscular atrophy confirmed by genetic testing demonstrating bi-allelic mutations in the survival motor neuron 1 (SMN1) gene as stated below [Gene Reviews, SMA, 2020]:
2. The patient is symptomatic, documentation of a genetic test confirms 2, 3 or 4 copies of the
SMN2 gene (Finkel, 2017) AND
3. Patient is not on permanent ventilator dependence (UTD, Bodamer 2021);
AND
4. Submission of medical records (e.g., chart notes, laboratory values) with the most recent results (< 1 month prior to request) documenting pretreatment baseline status to nusinersen therapy as demonstrated by at least one of the following exams (Finkel 2014-2017):
5. The patient is not concurrently enrolled in a clinical trial for any experimental therapy for spinal muscular atrophy.
AND
6. Prescribed by a neurologist with expertise in treating spinal muscular atrophy
Note: The concurrent use of nusinersen with onasemnogene abeparvovec-xioi and/or risdiplam Is not covered (see statement of non-coverage below).
Continuation of Treatment (approval for 6 months or 1 year)
Incremental reauthorization for nusinersen for up to 1 year may be considered if the following conditions are met (UTD, Bodamer 2021):
1. The patient was previously approved for nusinersen based on criteria cited above
2. Patient is not permanently ventilator-dependent on:
3. Submission of medical records (e.g., chart notes, laboratory values) with the most recent results (< 1 month prior to request) documenting a positive clinical response from pretreatment baseline status to nusinersen therapy as demonstrated by at least one of the following exams (Finkel 2014-2017):
4. Nusinersen is prescribed by or in consultation with, a neurologist with expertise in the treatment of SMA.
Dosing and Administration
The prescribed regimen must be within the U.S. Food and Drug Administration dosing of 12 mg (5 mL) administered intrathecally per treatment; the first 3 loading doses should be administered at 14-day intervals. The fourth loading dose should be administered 30 days after the third dose. A maintenance dose should be administered once every 4 months thereafter.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of Nusinersen does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of patients with type 0 and IV spinal muscular atrophy or for any other indication not described above.
For members with contracts without primary coverage criteria, the use of Nusinersen for the treatment of patients with type 0 and IV spinal muscular atrophy or for any other indication not described above is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The concurrent use of nusinersen with onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of patients with type 0 and IV spinal muscular atrophy or for any other indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, the concurrent use of nusinersen with onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of patients with type 0 and IV spinal muscular atrophy or for any other indication is considered investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The use of nusinersen after administration of onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of patients with type 0 and IV spinal muscular atrophy or for any other indication does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, the use of nusinersen after administration of onasemnogene abeparvovec-xioi and/or risdiplam for the treatment of patients with type 0 and IV spinal muscular atrophy or for any other indication is considered investigational. Investigational
services are specific contract exclusions in most member benefit certificates of coverage.
II Onasemnogene Abeparvovec-Xioi
Effective November 1, 2019, Prior Approval will be required for Onasemnogene Abeparvovec-XIOI (Zolgensma®).
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of Onasemnogene abeparvovec-xioi meets member benefit certificate primary coverage criteria
that there be scientific evidence of effectiveness for the treatment
of patients with infantile-onset or type I spinal muscular atrophy with a documented genetic diagnosis of spinal muscular atrophy.
1. Diagnosis of spinal muscular atrophy confirmed by genetic testing demonstrating bi-allelic mutations in the survival motor neuron 1 (SMN1) gene as stated below (Gene Reviews, SMA, 2020):
2. Documentation of onset of symptoms consistent with clinical diagnosis of type I spinal muscular atrophy less than 6 months of age (Mendell, 2017).
3. Documentation of a genetic test confirms no more than 2 copies of the
SMN2 gene (Mendell, 2017).
4. Patient is less than 6 months of age at the time of infusion of onasemnogene abeparvovec-xioi (Mendell, 2017).
5. Patient does not have advanced spinal muscular atrophy (e.g., complete paralysis of limbs, permanent ventilator dependence).
6. Baseline anti-adeno-associated virus serotype 9 (AAV9) antibody titers
< 1:50 (FDA Zolgensma).
7. Prescribed by a neurologist with expertise in treating spinal muscular atrophy.
Dosing and Administration
The recommended dosage of onasemnogene abeparvovec-xioi is 1.1 × 1014 vector genomes (vg) per kg of body weight. It should be administered as an intravenous infusion over 60 minutes. Systemic corticosteroids equivalent to oral prednisolone at 1 mg/kg should be administered according to the FDA approved prescribing label.
The FDA label states that "The safety and efficacy of ZOLGENSMA in patients with anti-AAV9 antibody titers above 1:50 have not been evaluated.” Baseline anti-AAV9 antibody testing is performed prior to infusion using. Retesting may be performed if anti-AAV9 antibody titers are reported as >1:50.
Liver function (clinical exam, AST, ALT, total bilirubin, prothrombin time), platelet counts and troponin-I levels should be monitored as per the prescribing label.
Where feasible, patient’s vaccination schedule should be adjusted to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec-xioi infusion.
Use of onasemnogene abeparvovec-xioi in premature neonates before reaching full term gestational age may not be recommended because concomitant treatment with corticosteroids may adversely affect neurological development.
Efficacy of onasemnogene abeparvovec-xioi in patients with c.859G>C variant in SMN2 gene has not been evaluated.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications. It will be expected that this therapy will be administered through a certified treatment location. Please see:
http://www.curesma.org/zolgensma-administration-sites.html for locations of administration.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The repeat treatment or ante-partum use of onasemnogene abeparvovec-xioi for the treatment of infantile-onset or type I spinal muscular atrophy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For those members without primary coverage criteria, the repeat treatment or ante-partum use of onasemnogene abeparvovec-xioi for the treatment of infantile-onset or type I spinal muscular atrophy is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The use of onasemnogene abeparvovec-xioi for any indication not described above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For those members without primary coverage criteria, the use of onasemnogene abeparvovec-xioi for any indication not described above is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Concurrent use of onasemnogene abeparvovec-xioi with nusinersen and/or risdiplam does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For those members without primary coverage criteria, the concurrent use of onasemnogene abeparvovec-xioi with nusinersen and/or risdiplam is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Use of nusinersen and/or risdiplam after administration of onasemnogene abeparvovec-xioi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For those members without primary coverage criteria, the use of nusinersen and/or risdiplam after administration of onasemnogene abeparvovec-xioi is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
III Risdiplam
The FDA has deemed this drug to be appropriate for self-administration or administration by a caregiver (i.e., not a
healthcare professional). Therefore, the use of Risdiplam is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage. This policy applies to members whose plan utilizes AR BCBS pharmacy and has Risdiplam as a formulary option.
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of Risdiplam (Evrysdi™) meets member benefit certificate primary coverage criteria that there be scientific evidence for effectiveness for the treatment
of patients type I, type II and type III SMA if all the following conditions are met:
Initial approval is for 6 months.
1. Diagnosis of spinal muscular atrophy confirmed by genetic testing demonstrating bi-allelic mutations in the survival motor neuron 1 (SMN1) gene as stated below (Gene Reviews, SMA 2020):
2. Individual meets one of the following (Mercuri 2020):
3. Individual age is less than 25 years of age (Mercuri, 2020).
4. Patient is not on permanent ventilator dependence
5. The patient is not concurrently enrolled in a clinical trial for any experimental therapy for spinal muscular atrophy.
6. Prescribed by a neurologist with expertise in treating spinal muscular atrophy
7. The concurrent use of risdiplam with onasemnogene abeparvovec-xioi and/or nusinersen does not meet member benefit certificate primary coverage criteria
Continuation of Treatment (approval for 6 months or 1 year)
Incremental reauthorization for risdiplam for 1 year may be considered
medically necessary if the following conditions 1 and 2 are met:
1. The patient was previously approved for risdiplam based on criteria cited above
2. Patient is not dependent on either of the following:
3. Submission of medical records (e.g., chart notes, laboratory values) with the most recent results (< 1 month prior to request) documenting a positive clinical response from pretreatment baseline status to nusinersen therapy as demonstrated by at least one of the following exams:
4. Nusinersen is prescribed by or in consultation with, a neurologist with expertise in the treatment of SMA.
Dosage and Administration
The prescribed regimen must be within the U.S. Food and Drug Administration guidelines. Risdiplam is dosed by age and body weight.
Age and body weight Daily Dosage
2 months to < 2 yrs of age 0.2 mg/kg
2 yrs and older weighing < 20 kg 0.25 mg/kg
2 yrs and older weighing > 20 kg 5 mg
Risdiplam should be avoided in patients with hepatic impairment.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Use of risdiplam for any indication not described above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For those members without primary coverage criteria, the use of risdiplam for any indication not described above is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The concurrent use of risdiplam with onasemnogene abeparvovec-xioi and/or nusinersen does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For those members without primary coverage criteria, the concurrent use of risdiplam with onasemnogene abeparvovec-xioi and/or nusinersen is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Use of risdiplam after administration of onasemnogene abeparvovec-xioi does not meet member benefit certificate primary coverage criteria
that there be scientific evidence of effectiveness.
For those members without primary coverage criteria, the use of risdiplam after administration of onasemnogene abeparvovec-xioi is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Due to the detail of the policy statement, the document containing the coverage statements for dates prior to March 16, 2022 are not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com
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| Rationale: |
Nusinersen
Randomized Studies
The pivotal trial was a multicenter randomized, double-blind trial, Assess the Efficacy and Safety of Nusinersen in Infants with spinal muscular atrophy (ENDEAR; NCT02193074) in which 121 infants with a documented genetic diagnosis of spinal muscular atrophy with symptom onset before 6 months of age were randomized 2:1 to nusinersen (n=80) or to sham injection (n=41) (Finkel RS, 2017). Nusinersen was approved based on planned interim analysis of 82 patients who completed at least 183 days of treatment or died or withdrew. Patients' demographics at baseline were 44% male, and 87% white, with a median length of treatment of 261 days (range, 6-442 days). The primary endpoint was the proportion of motor milestone responders.
The trial met its coprimary endpoints, with nusinersen showing clinically meaningful improvement in motor milestones and probability of surviving or receiving permanent-assisted ventilation compared with sham control. The median time to death or the use of permanent-assisted ventilation was 22.6 weeks in the control group and was not reached in the nusinersen group. Multiple secondary endpoints showed a consistency in treatment effect favoring nusinersen over sham control. It is notable that half of the nusinersen-treated subjects did not achieve the primary endpoint, motor milestone response. The FDA (based on interim analysis) reported "although the response was clearly important, perhaps life-changing in few cases (6% of patients gained the ability to sit without assistance, a feat that almost never occurs in individuals with only 2 copies of the SMN2 gene), the majority of patients had a modest response or no response at all." Further, the FDA noted that 94% of patients were not able to sit, no patient was able to stand unassisted, and no patient progressed to walking. On the motor response rate (using the Hammersmith Infant Neurological Examination), the FDA concluded that, on average, mean motor milestone scores in nusinersen treated patients improved from approximately 1 point (before treatment) to approximately 4 points at 12 months-a difference of 3 points over 6 months. At 12 months, a healthy baby would achieve a motor milestone score of 22. Thus, nusinersen is a disease-modifying treatment and not a cure. While no irreversible harms were observed in the preliminary clinical data analyzed by the FDA before drug approval, the FDA noted that such harms could not be ruled out based on animal toxicity data (potential of neurotoxicity) and class effects of antisense oligonucleotides (coagulation abnormalities, thrombocytopenia, renal toxicity). Given the limited data on the durability of response, long-term data documenting safety and efficacy is needed.
Type II and Ill Spinal Muscular Atrophy
Similar to ENDEAR, CHERISH (A Study to Assess the Efficacy and Safety of Nusinersen in Participants With Later-onset Spinal Muscular Atrophy (SMA)) (Mercuri E, 2018) was also designed as a multicenter, randomized, double-blind trial that evaluated 126 nonambulatory patients with genetic documentation of Sq spinal muscular atrophy (a homozygous deletion, variant, or compound heterozygote in SMN1) with the onset of signs and symptoms at more than 6 months and between ages 2 and 12 years at screening as well as the presence of the following features at screening: the ability to sit independently, no history of the ability to walk independently (defined as the ability to walk 15 feet unaided), and a Hammersmith Functional Motor Scale Expanded score between 10 and 54. Children were excluded if they had a severe contracture, evidence of severe scoliosis on radiography, respiratory insufficiency, or a gastric tube placed to provide adequate nutrition. Because of the strict inclusion and exclusion criteria to enroll a homogenous and younger patient population (median age from 4 to 3 years in treatment and control group, respectively), the results from this trial have limited generalizability to type II and Ill spinal muscular atrophy patients generally seen in clinical practice.
The primary endpoint was change in Hammersmith Functional Motor Scale Expanded score compared with baseline. Hammersmith Functional Motor Scale Expanded scores range from O to 66, with higher scores indicating better motor function. Results are summarized in Table 15. The trial met its primary endpoints with nusinersen showing clinically meaningful improvement in mean Hammersmith Functional Motor Scale Expanded scores compared with sham control. In terms of responder analysis, a higher percentage of children in the nusinersen group (57%) than in the control group (26%; p<0.001) had an increase from baseline to month 15 in the Hammersmith Functional Motor Scale Expanded score of at least 3 points, which was considered meaningful. Multiple secondary endpoints summarized in Table 15 showed a consistency in treatment effect favoring nusinersen compared with sham control. Approximately a quarter of placebo patients reported clinically meaningful improvements in Hammersmith Functional Motor Scale Expanded scores at 15 months, which is most likely a combination of the placebo effect, the learning curve for the assessment of the Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores, and initial developmental gains, particularly in younger children. The initial improvement in Hammersmith Functional Motor Scale Expanded scores in the placebo arm was short-lived and showed a declining trend starting at 6 months and continuing to the end of the trial (i.e., 15 months). Analyses of the magnitude of change in the Hammersmith Functional Motor Scale Expanded score stratified by age and disease duration (data not shown) revealed greater, improvements in younger children and in those who received treatment earlier in their disease course, respectively. The overall incidences of adverse events and moderate and serious adverse events were similar for the nusinersen group and the control group (93% and 100% vs 46% and 55%, respectively). Adverse events with an incidence of 5 or more percentage points higher in the nusinersen group than in the control group were pyrexia, headache, vomiting, back pain, and epistaxis. Given the limited data on the durability of response, long-term data documenting safety and efficacy are needed.
Similar to ENDEAR trial, the confirmatory phase 3 CHERISH trial was terminated early because the results of a preplanned interim analysis met the primary endpoint of efficacy.(Biogen, 2019) However, in the prespecified interim analysis, data for the 15-month time-point for Hammersmith Functional Motor Scale Expanded score were missing in 58% (49/84) and 55% (23/42) patients in the nusinersen and control group, respectively, and was imputed using the use of a multiple imputation method to conduct an intention-to-treat analysis. The missing data were largely due to patients who had not completed their 15-month visit at the time of analysis. In the final analysis, the proportions of missing data for Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores were imputed for 21% (18/84) and 19% (8/42) patients in the nusinersen and control group, respectively, and imputed using multiple imputation method to conduct an intention-to-treat analysis. For all other outcomes, only the observed data were included. The authors conducted multiple sensitivity analyses including (1) multiple imputations using mixed-effects model for repeated measures, (2) only completers (per protocol), (3) last observation carried forward approach, and (4) for children who had a missing 15-month assessment and discontinued due to treatment failure or death, the worst of the last observed value or the baseline value was imputed. The intergroup difference between the least-squares mean change from baseline to month 15 remained statistically significant in favor of nusinersen in all 4 scenarios with highest treatment effect (change, 5.2) in the "completers only analysis."
Type 0 or IV Spinal Muscular Atrophy
There are currently no studies assessing the efficacy and safety of nusinersen in patients with type 0 or IV spinal muscular atrophy.
Onasemnogene Abeparvovec-Xioi
The clinical development program of onasemnogene abeparvovec-xioi for patients with symptomatic spinal muscular atrophy type I includes 4 prospective cohort studies; 2 dose-finding study, 2 phase 3 confirmatory studies (STRIVE-US: Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1; STRIVE EU: Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 ), and 1 long-term follow-up study (START: Long-Term Follow-up Study for Patients From AVXS-101-CL-101). These trials will enroll a total of 65 patients with symptomatic spinal muscular atrophy type I. Of these 4 trials, only the dose-finding phase 1 study has been completed and has reported 2-year follow-up data. (Mendell JR, et al. 2017);(Al-Zaidy S, Kolb SJ, et al. 2019); (Al-Zaidy S, Pickard AS, et al. 2019); Lowes LP, et al. 2019)
In the phase 1 study, 12 of 15 infants received the proposed therapeutic dose while 3 received a minimally effective dose. At a median follow-up ranging from 30.7 to 27.8 months (based on 2 dose cohorts), all 15 patients survived and none of the 12 patients who received the proposed therapeutic dose required permanent ventilation at the 2-year follow-up. Based on the known natural history of patients with spinal muscular atrophy type I with 2 copies of the SMN2 gene, 8% of patients are expected to survive beyond 2 years without ventilation. In terms of motor functions, all 12 patients achieved at least 1 motor milestone, with 92% of those achieving scores greater than 40 on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Compared with the known natural history, attaining a CHOP INTEND score greater than 40 is rare (Finkel RS, et al. 2016), and patients experience a 10.7-point drop in CHOP INTEND scores between 6 to 12 months of age. Treatment-related asymptomatic transient elevated liver function enzymes (categorized as serious adverse events) were reported in 2 patients. The early data in a small number of patients diagnosed with spinal muscular atrophy type I is indicative of positive impact on survival and motor functions that are durable up to 2 years.
The FDA approval was based on a pooled analysis of 21 patients with 2 copies of SMN2 from the pivotal phase I and STRIVE-US trial with a data analysis cut off of March 2019. Efficacy was established on the basis of survival, and achievement of developmental motor milestones such as sitting without support. Comparison of the results of the ongoing clinical trial to available natural history data of patients with infantile-onset spinal muscular atrophy was the primary evidence for effectiveness of onasemnogene abeparvovec-xioi.
While the current evidence for symptomatic type I spinal muscular atrophy patients is limited to patients with 2 copies of SMN2, approximately 20% of type I spinal muscular atrophy patients may have 3 copies of SMN2 (Feldkotter M, et al. 2002). Given the treatment effect observed in symptomatic patients, it is possible that patients with 3 copies of SMN2 may experience a clinically meaningful benefit. However, there is no published evidence to support such a hypothesis. Further, there is no published data that supports clinical benefit in Type I spinal muscular atrophy patients who are administered onasemnogene abeparvovec-xioi after 6 months of age.
ICER Report
In summarizing the uncertainties of the clinical evidence, the ICER Report noted considerable uncertainty in the generalizability of the results and in the long-term durability and tolerability of treatment. Further, the Report notes additional uncertainty related to the possibility of loss of transgene expression over time and subsequent treatment pathway. The Report also noted that some patients in the pivotal trial subsequently received nusinersen, but the effects of combination or sequential therapies have not been well studied.
Ongoing Clinical trials for Onasemnogene abeparvovec-xioi
STRONG (NCT03381729) – Phase 1 trial of AVXS-101 in SMA type II using the intrathecal (IT) formulation. Ongoing; estimated completion – August 2019
SPR1NT (NCT03505099)– Phase 3, multi-national study that will evaluate IV delivery of AVXS-101 in patients less than 6 weeks old with SMA types 1, 2, or 3 who have 2 or 3 copies of SMN2 and who are pre-symptomatic. Ongoing; estimated completion – April 2023
STR1VE U.S. trial (NCT03306277) – Phase 3, evaluation of the efficacy and safety of AVXS-101 Ongoing; estimated completion – March 2020
STR1VE E.U. trial (NCT03461289) – Phase 3, evaluation of the efficacy and safety of AVXS-101 Ongoing; estimated completion – November 2020
START (NCT03421977) – Phase 4 Ongoing; estimated completion – December 2033
Risdiplam
Spinal Muscular Atrophy Type I
For individuals who have symptomatic SMA type I (infantile onset) who receive risdiplam, the evidence includes 1 single arm prospective phase 2/3 FIREFISH study. Relevant outcomes are overall survival, change in disease status, functional outcomes, health status measures, quality of life, and treatment-related mortality and morbidity. Results of a part 1 study (dose-finding and exploratory) in which 4 patients received low dose and 17 patients received high dose risdiplam are available. The results of the part 1 study (dose-finding and exploratory) showed 41 % (7 of 17 infants) were able to sit without support for at least 5 seconds as assessed by BSID-I11 after 12 months of treatment. After a minimum follow-up of 12 and 23 months of treatment with risdiplam, 90% (19/21) and 81% (17/21) of patients were alive without permanent ventilation. The observed treatment effect on motor functions and event-free survival is beyond what typical is based on the known natural history of patients with SMA type I with 2 copies of SMN2. However, there is limited data to assess the long-term durability of treatment effect as well as safety related to adverse events that are rare or have delayed onset.
Spinal Muscular Atrophy Type II and Ill
The evidence for pediatric or adult patients (2-25 years old) with type II or Ill SMA patients includes the ongoing double blind, 2-part, placebo-controlled SUNFISH study.
Part 1 was dose-finding and exploratory in 51 patients for 12 weeks. Part 2 was the randomized, double-blind, placebo controlled in which patients received risdiplam or placebo for 12 months. After 12 months, placebo recipients were switched to risdiplam for next 12 months while those receiving risdiplam continued to receive until 24 months. This trial included patient population who previously were excluded from clinical trials, such as ages up to 25, severe scoliosis, and low baseline function. At baseline, 67% of patients had scoliosis (32% of them with severe scoliosis). Results of Part 2 are discussed next. The least square mean change in MFM-32 from baseline was greater in patients receiving risdiplam compared with placebo with a difference of 1.55 (95% Cl: 0.30 to 2.81). Responder analysis (using a threshold of increase in 3 or more points in MFM-32 as being clinically meaningful) showed that 38% of those receiving risdiplam met the criteria of achieving a clinically meaningful improvement in motor function compared to 24% in the placebo arm. Clinical benefit was also observed in the upper limb function as measured by revised upper limb module (RULM). Risdiplam treated patients had a mean 1.6-point improvement from baseline at month 12 compared to no mean score change in the placebo group (p=0.047). In general, increases on motor function tests would not be expected in the natural history of Type 2 and 3 SMA, and the differences observed between patients treated with risdiplam and those on placebo are considered clinically meaningful. (Center for Drug Evaluation and Research, 2020)
For MFM-32, and RULM subgroup analysis based on SMA subtype showed treatment differences in favor of risdiplam versus placebo in both SMS type 2 and 3. Subgroup analysis based on SMN2 copy number showed treatment differences in favor of risdiplam versus placebo based upon point estimates in individuals with 3 and 4 copies. However, the confidence intervals were wide and specifically for individuals with SMN2 copy number 4, the confidence interval was inclusive of negative treatment effect. There were only 4 participants with 2 SMN2 2 copy numbers and there was a negative treatment effect.
UpToDate: Bodamer
Prognosis
SMA encompasses a spectrum of phenotypes ranging from severe forms with early onset to milder forms with later onset The natural history of SMA according to phenotype is summarized as follows:
The eventual impact of novel disease-modifying therapy (eg, nusinersen) for ameliorating the expected course of SMA is uncertain.
Limited data suggest that survival has increased in patients with SMA type 1 born from 1995 through 2006 compared with those born from 1980 to 1994. Ventilation for >16 hours a day, use of mechanical insufflation-exsufflation device, and gastrostomy tube feeding were significantly and independently associated with prolonged survival, while year of birth was not. Thus, longer survival in the later time period appears to be related to more aggressive care.
Ongoing Clinical trials for Risdiplam
Firefish (NCT02913482) – Phase 2/3 open-label single arm study for Type 1 SMA. It is ongoing and unpublished.
Sunfish (NCT02908685) – Phase 2/3 RCT double-blind, placebo-controlled study for Type 2 and 3 SMA. It in ongoing and unpublished, expected completion September 2023.
Jewelfish (NCT03032172) – For safety and tolerability and is an open-label single arm study for Treatment-experienced patients with SMA. It is ongoing and unpublished, expected date of completion is December 2021
Rainbowfish (NCT03779334) – For efficacy and safety and is an open-label single arm study for those pre-symptomatic infants from birth to 6 weeks. It is ongoing and unpublished, expected date of completion is October 2021.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2022. No new literature was identified that would prompt a change in the coverage statement.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2023.
October 2023 Update
Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of
≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of
≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67-4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI - 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment. (Oskoui M, Day JW, Deconinck N, 2023)
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2024. No new literature was identified that would prompt a change in the coverage statement.
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2025.
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[package insert](2019) Zolgensma® (onasemnogene abeparvovec-xioi) Bannockburn, IL: AveXis, Inc.; 2019. AI-Zaidy S, Pickard AS, Katha K, et al.(2019) Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. Feb 2019; 54(2): 179-185. PMID 30548438 AI-Zaidy SA, Kolb SJ, Lowes L, et al.(2019) AVXS-101 (Onasemnogene Abeparvovec) for SMA1: Comparative Study with a Prospective Natural History Cohort. J Neuromuscul Dis. 2019; 6(3): 307-317. PMID 31381526 Biogen Inc.(2016) Highlights of Prescribing Information: Spinraza (nusinersen) injection, for intrathecal use: Prescribing label. 2016; https://www.spinraza.com/contenUdam/commercial/specialty/spinraza/caregiver/en _ us/pdf/spinrazaprescribing-information. pdf. Accessed August 27, 2020 Biogen, RTI Health Solutions.(2019) Formulary Submission Dossier: Spinraza (Nusinersen) for Spinal Muscular Atrophy (NS-US-0199). Cambridge, MA: Biogen; 2019 December Bodamer, OA,(2021) Spinal Muscular Atrophy, UpToDate August, 2021 Cure SMA Available at: http://www.curesma.org/sma/. Accessed June 17, 2019 De Vivo DC, Bertini E, Swoboda KJ, et al.(2019) Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. Nov 2019; 29(11): 842-856. PMID 31704158 Feldkotter M, Schwarzer V, Wirth R, et al.(2002) Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. Feb 2002;70(2):358-368. PMID 11791208 Finkel RS, Chiriboga CA, Vajsar J, et al.(2016) Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. Dec 17 2016; 388(10063): 3017-3026. PMID 27939059 Finkel RS, McDermott MP, Kaufmann P, et al.(2014) Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. Aug 26 2014;83(9):810-817. PMID 25080519 Finkel RS, Mercuri E, Darras BT, et al.(2017) Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. Nov 02 2017; 377(18): 1723-1732. PMID 29091570 Foust KD, Nurre E, Montgomery CL, et al.(2009) lntravascular MV 9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. Jan 2009; 27(1 ): 59-65. PMID 19098898 Genentech.(2020) Highlights of Prescribing Information: EVRYSDI (risdiplam) for oral solution: Prescribing label. 2020; ; https://www.gene.com/download/pdf/evrysdi_prescribing.pdf. Accessed August 12, 2020. Glanzman AM, Mazzone E, Main M, et al.(2010) The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability. Neuromuscul Disord. Mar 2010;20(3):155-161. PMID 20074952 Institute for Clinical and Evidence Review. Spinraza® and Zolgensma® for Spinal Muscular Atrophy: Effectiveness and Value (Final Evidence Report April 3, 2019; Updated May 24, 2019). 2019; https://icer-review.org/wp-content/uploads/2018/07/ICER_SMA_Final_Evidence_Report_052419.pdf. Accessed May 28, 2019. Kolb SJ, Kissel JT.(2015) Spinal Muscular Atrophy. Neuol Clin 2015 Nov; 33(4):831-46: 10.106/j.ncl.2015.07.004 Lefebvre S, Burlet P, Liu Q, et al.(1997) Correlation between severity and SMN protein level in spinal muscular atrophy. Genet. Jul 1997;16(3):265-269. PMID 9207792 Lorson CL, Hahnen E, Androphy EJ, et al.(1999) A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci U S A. May 25 1999;96(11):6307-6311. PMID 10339583 Lowes LP, Alfano LN, Arnold WD, et al.(2019) Impact of Age and Motor Function in a Phase 1/2A Study of Infants with SMA Type 1 Receiving Single-Dose Gene Replacement Therapy. Pediatr Neural. Sep 2019; 98: 39-45. PMID 31277975 Mendell JR, Al-Zaidy S, Shell R, et al.(2017) Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy N Engl J Med 2017; 377(18):1713-22. Mercuri E, Darras BT, Chiriboga CA, et al.(2018) Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. N Engl J Med. Feb 15 2018; 378(7): 625-635. PMID 29443664 Muscular Dystrophy Association(2017) Spinal Muscular Atrophy https://www.mda.org/disease/spinal-muscularatrophy. Accessed March 12, 2020 National Organization for Rare Disorders, Russman B(2017) Spinal Muscular Atrophy https://rarediseases.org/rare-diseases/spinal-muscular-atrophy/. Accessed January 18, 2017. NICE (National Institute for Health and Care Excellence): Technology appraisal guidance: Nusinersen for treating spinal muscular atrophy. Published July 24, 2019. Accessed on August 27, 2020. https://www.nice.org.uk/guidance/ta588 Oskoui M, Day JW, Deconinck N, et.al.(2023) Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA). J Neurol. 2023 May;270(5):2531-2546. doi: 10.1007/s00415-023-11560-1. Epub 2023 Feb 3. Erratum in: J Neurol. 2023 Apr 18;: PMID: 36735057; PMCID: PMC9897618. Prior TW, Krainer AR, Hua Y, et al.(2009) A positive modifier of spinal muscular atrophy in the SMN2 gene. Am J Hum Genet. Sep 2009; 85(3): 408-13. PMID 19716110 Prior TW, Snyder PJ, Rink BD, et al.(2010) Newborn and carrier screening for spinal muscular atrophy. Am J Med Genet A. Jul 2010;152A(7):1608-1616. PMID 20578137 Sugarman EA, Nagan N, Zhu H, et al(2012) Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. Jan 2012;20(1):27-32. PMID 21811307 Thomas W Prior, PhD, FACMG, Meganne E Leach, MSN, PNP, and Erika Finanger, MD,(2020) Gene Reviews: Spinal Muscular Atrophy, Initial Posting: February 24, 2000; Last Revision: December 3, 2020. Accessed: September 29, 2021. Valeri CF, Ning K, Wyles M, et al.(2010) Systemic delivery of scMV 9 expressing SMN prolongs survival in a model of spinal muscular atrophy Sci Transl Med. Jun 09 2010; 2(35): 35ra42. PMID 20538619 Wang CH, Finkel RS, Bertini ES, et al.(2007) Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. Aug 2007;22(8):1027-1049. PMID 17761659 Zerres K, Rudnik-Schoneborn S(1995) Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. May 1995;52(5):518-523. |
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