Most expensive gene therapy globally approved

Most patients with the inheritable genetic defect in the SMN1 (survival motor neuron 1) gene, leading to progressive muscle weakness and paralysis, die before they are two years old. Novartis’ subsidiary AveXis Inc. on Friday received FDA approval for Zolgensma (AVXS-101) as a treatment of SMA patients less than 2 years of age, even with presymptomatic disease. According to claims of Novartis a single injection can cure the disease. A long-term follow up study (15 years) is ongoing. The company announced to set the price at $2.125m per dose in the US, making it the world’s most expensive drug.

AVXS-101 is a self-complementary AAV9 carrying the SMN gene under the control of a hybrid CMV enhancer/chicken-?-actin promoter. Data from the ongoing open-label, single-arm Phase III STR1VE trial show prolonged event-free survival, increases in motor function and significant milestone achievement in 21 patients with a bi-allelic SMN1 gene deletion or point mutations, consistent with results from a open-label, single-arm, ascending-dose Phase I safety trial (START) in 15 patients, which demonstrated significant improval in motor function lasting for four years at least in some, but not most cases. In the STR1VE trial 13 of 15 Zolgensma-treated infants survived to 13.6 months without requiring permanent ventilation. As with other gene therapies, higher numbers of treated patients will show the amount of immune reactions against the AAV9 viral vector and the the value of Zolgensma in the majority of patient.

Competition, however is high in the $4bn marktet of SMA treatments. AVXS-101 will compete against Biogen’s FDA-approved drug Spinraza, a disease-modifying antisense drug with a broader label and more than 7,000 patients treated, some for as long as six years. Spinraza is approved for all types of SMA — from the sickest type 1 infants to adults with milder forms of the disease where loss of muscle function starts later and is more gradual. The drug requires regular spinal infusions costing $750,000 in the first year and $375,000 annually thereafter, for life. Sales last year totaled $1.7bn. Zolgensma may be more convenient than Spinraza, but Roche is developing a daily pill for SMA, a SMN 2 gene splicing modifier called risdiplam that could reach the market in 2020 and which led to survival of 88% of patients and the ability of one infant to stand unassisted, a milestone in SMA treatment.

The most commonly observed adverse events were elevated aminotransferases and vomiting. Efficacy was established on the basis of survival, and achievement of developmental motor milestones such as sitting without support. Survival was defined as time from birth to either death or permanent ventilation as defined by requirement for invasive ventilation, or respiratory assistance for 16 or more hours per day for 14 or more days.

High-priced orphan gene therapies are expected to put health systems under pressure as their producers demand high prices for potentially curative treatments which have only been validated in a low number of patients upon approval.