On May 24, 2019, the FDA approved Onasemnogene abeparvovec, a drug based on adeno-associated virus type 9 vector, for the treatment of spinal cords caused by an allelic mutation in the motor neuron survival gene under 2 years of age. Childhood patients with muscular atrophy. The trade name is Zolgensma®.
The FDA has successively granted the drug rapid channel, breakthrough therapy, rare pediatric disease treatment drugs, priority review and other related qualifications due to the urgent need for clinical and hope to cure children with SMA caused by the 1 double allele mutation of SMN gene, which greatly shortened the qualification. The review time, from the Zolgensma ® IND application to the FDA approved listing, lasted only 8 years.
Zolgensma® is a gene therapy based on adeno-associated virus type 9 (AAV9) vector. The adeno-associated virus (AAV) vector has low pathogenicity, weak immunogenicity to the host, long-term stable expression, and strong cell and tissue specificity. According to the different serotypes, the commonly used adeno-associated viruses can be divided into 6 types: AAV1, AAV2, AAV5, AAV6, AAV8, AAV9; among them, AAV9 can pass the blood-brain barrier more easily than other viral vectors, and can be transported after intravenous injection. To the central nervous system, infection of about 60% of motor neurons .
Novartis/AveXis' Zolgensma® uses AAV9 from Regenxbio's NAV® gene delivery technology platform, which utilizes a viral surface shell that binds to galactose on the cell surface, allowing AAV9 to cross the blood-brain barrier and contain the SMN gene through the blood-brain barrier. The AAV9 vector is delivered to central nervous system motor neurons.
In January 2018, RegenxBio and AveXis expanded and revised the SMA development and commercialization license agreement. Under the terms of the agreement, AveXis will receive a worldwide exclusive license to develop SMA from Regenxbio's NAV® Gene Delivery Technology Platform. To this end, AveXis needs to pay Regenxbio a down payment of $80 million, an additional $30 million in additional payments after one year, and an additional $30 million in two years, plus payment and royalties under the original license agreement. When Zolgensma®'s cumulative sales reach $1 billion, Novartis will pay up to $80 million in potential commercial milestone payments.
In April 2018, Novartis acquired AveXis at a price of $218 per share for a total acquisition of $8.7 billion to expand Novartis' position in gene therapy.
In June 2018, RegenxBio received a $100 million accelerated license payment, which included an annual fee of $60 million and AveXis' $40 million commercial milestone. The early R&D investment and high cost are doomed to the high price of Zolgensma®, and Novartis's price is Zolgensma®. The cost of one-time injection treatment is as high as 2.125 million US dollars, making it the most expensive drug in history.