Gene therapy’s next installment

Sky-high-priced gene therapies face slow uptake and market failure unless healthcare payers and drug makers can find common ground in ‘pay-for-performance’ reimbursement.

At the end of May, Zolgensma was approved by the US Food and Drug Administration (FDA) as a gene therapy for children up to the age of two with spinal muscular atrophy (SMA). This was followed on June 3 by the European Commission’s marketing authorization for Zynteglo, a gene therapy against transfusion-dependent β-thalassemia in patients 12 years or older. While patient groups hailed the news, the price of these products provoked sticker shock: Zolgensma costs $2.1 million; Zynteglo $1.8 million. They are the two most expensive medicines in the world. Finding a way for resource-constrained healthcare systems to pay for them is an ongoing conundrum. The good news is that a new type of reimbursement model—pay-for-performance milestones or installments—may offer a solution.

Zolgensma is a one-time, intravenous injection of human survival motor neuron gene 1 (SMN1) under the control of chicken beta-actin promoter delivered by adeno-associated virus serotype 9 (AAV9). It was developed by Nationwide Children’s Hospital’s spinout Avexis, sailed through regulatory review on the back of two trials with a combined 35 patients and was ultimately being gobbled up by Novartis for $8.7 billion in 2018. Zynteglo is Bluebird Bio’s single injection of autologous CD34+ cells transduced ex vivo with the gene encoding βA-T87Q-globin via a lentiviral vector pseudotyped with vesicular stomatitis virus glycoprotein G. It rocketed through conditional approval at the European Medicines Agency in just 150 days on the basis of three trials involving a combined total of 41 patients.