Appeal type: Medical Necessity
Decision: Upheld

Nature of Statutory Criteria/Case Summary: The parent of an enrollee has requested authorization and coverage for the medication Spinraza.Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal motor neurons. The condition causes significant morbidity and mortality in affected children, who have profound weakness affecting the limbs and also the respiratory muscles. SMA is caused by low levels of survival motor neuron (SMN) protein owing to deletions or mutations of the SMN1 gene. An almost identical gene SMN2, present on the same chromosome, produces a smaller, truncated protein (SMN2) because of skipping of exon 7 from translation due to translation silent C6U substitution in exon 7 of SMN2 pre-mRNA transcript. Only 10% of the SMN2 mRNAs produce full length SMN2 protein by including exon 7 in healthy individuals. A large deletion or sometimes a point mutation in SMN1 gene is responsible for SMA. In this case the number of copies of SMN2 genes in an individual determines the severity of disease (the more the number of copies the less severe the disease). In December of 2016, nusinersen (Spinraza) was approved by the Federal Drug Administration (FDA) in the United States, providing the potential for correction of SMN2 exon 7 splicing as a treatment for SMA. Researchers have published the results of a study on AVXS-101, a gene replacement therapy in children with genetically confirmed SMA type 1. All 12 patients in the study completed the study. Seven infants did not require noninvasive ventilation (NIV) by study completion. Eleven patients had stable or improved swallow function, demonstrated by the ability to feed orally; eleven patients were able to speak. Eleven patients achieved full head control and sitting unassisted and two patients were walking independently. The authors concluded that AVXS-101 treatment in SMA1 was associated with reduced pulmonary and nutritional support requirements, improved motor function, and decreased hospitalization rate over the follow-up period. Others attempted to compare outcomes in children with SMA1 who were treated with AVXS-101 with those treated with nusinersen. Using Baseyian analysis, they concluded that indirect comparison (AVXS-101-CL-101 vs. ENDEAR) among symptomatic SMA type 1 infants suggests that AVXS-101 may have an efficacy advantage relative to nusinersen for overall survival, independence from permanent assisted ventilation, motor function, and motor milestones.In this case, the patient was entered into a clinical trial of AVXS-101, and there is now a request for Spinraza (nusinersen). At the present time, there are no published studies on outcomes of children who have received gene replacement therapy in the form of AVXS-101 and are subsequently treated with nusinersen. A recent Cure SMA presentation raised several issues regarding considerations for combination therapies in the treatment of SMA. The presenters questioned whether the treatments were safe when used together, whether there was additive clinical benefit, and if that benefit outweighs the risk of using two SMN enhancement drugs in combination. Additional unanswered questions were whether one drug reduces efficacy or availability of the other, and whether treatments could readily be co-administered. Pharmacological questions included if the drugs worked by different biological mechanisms, and if SMN levels were increased together over either drug alone. Further questions were whether the proposed drugs targeted different cells, and if two SMN enhancement drugs provide longer duration of effect when used together. The presenters noted that interpretation of clinical trials with two combination therapies will be more challenging. Under these circumstances, in which there are no published reports of Spinraza being used in children who have already been treated with AVXS-101, and in which neither the safety nor efficacy of using the two drugs in combination have been established, the requested medication Spinraza is not medically necessary to treat the patients medical condition.Final Result: The reviewer determined that the requested medication is not medically necessary for treatment of the patients medical condition. Therefore, the Health Plans denial should be upheld.Credentials/Qualifications: The reviewer is board certified in pediatrics and neurology with special qualification in child neurology, and is actively practicing. The reviewer is an expert in the treatment of the enrollees medical condition and knowledgeable about the proposed treatment through recent or current actual clinical experience treating those with the same or a similar medical condition.