Btobioinnovation.com
Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation jcm9144@gmail.com
SPECIAL REPORT #23
US FDA approves Zolgnesma®, the world most expensive drug at $2.1 million
Last week the US FDA approved Novartis Zolgensma®, a gene therapy for the treatment of patients younger than two years of age who have been diagnosed with spinal muscular atrophy (SMA) and who were pre-symptomatic at diagnosis. The clinical trials on which Zolgensma® the approval was based involves just 36 people. Novartis has announced that it was pricing the one-time treatment at a record high of $2.125 million.
SMA, is a genetic disease that causes debilitating muscle weakness and paralysis and is a leading cause of infant mortality. About 1 in 11,000 babies are born with spinal muscular atrophy and children with SMN1 (Survival of Motor Neuron type often die before they turn the age of two. Zolgensma® was designed to address the genetic root cause of SMA by providing a fully functional copy of the defective SMN1 gene in order to stop disease progression with a single, one-time infusion. This treatment, which was pioneered by Dr. Martine Barkats, now at the Institut de Myologie in Paris (France) while she was a research scientist at Généthon in Evry (France) back in 2004, uses the viral vector AAV9 to introduce the corrected SMN1 gene. The drug was developed by AveXis and a full license agreement has been concluded between AveXis and Généthon in March 2018. In April 2018, Novartis acquired AveXis for $8.7 billion with the intention to transform care in SMA and expand its position as a gene therapy and a Neuroscience leader.
Over the last weeks there has been an intensive debate over what a gene therapy is worth and Novartis had been rumored to estimate Zolgensma® to be cost-effective at up to $5 million per patient. A recent review by the US independent price watchdog ICER (Institute for Clinical and Economic Review) concluded that this estimate was excessive. The company now has decided to roll out the drug in the US with a list price of $2.125 million per treatment. Novartis was quick to point out that the price comes out at $425,000 per year for five years which is far less that the 10-year cost of current Biogen’s Spinraza, approved in late 2016. Spinraza requires infusion into the spinal canal every four months. Its list price of $750,000 for the initial year and $375,000 annually for another nine years would bring the total cost at $4.125 million assuming the price is never hiked.
At this stage it is worthwhile the pinpoint at the difference between the two drugs. Zolgensma® uses a viral vector to inject the malfunctioning genetic SMN1 code directly in the targeted cells, namely the moto neuron cells which then start producing the normal SMN1 protein by themselves. The result is a cure from a one-time treatment. Spinraza is an antisense oligonucleotide which binds to RNA genetic code and blocks the transcription at a given spot. In SMA patients, SMN1 which usually codes for full SMN is mutated and does not work because of a “stop” code right before a critical part of the gene coding for SMN is transcribed. Spinraza is blocking this “stop” code and allows the transcription to continue to produce a full SMN protein from the remaining SMN2 gene.
Quoting Mayer Winkler from Seeking Alpha, one could said: “Would you rather Buy a Gene from Novartis’ Zolgensma® or Rent a Gene from Biogen’ Spinraza.” Both drugs have different features in terms of efficacy and side effects. Zolgensma® requires a one-time treatment and no maintenance with half price of Spinraza. But Zolgensma® is only applicable to about 80% of SMA patients because some have an antibody against the virus used to deliver the gene. In addition, Zolgensma® comes with a warning for acute serious liver injury. Spinraza works in all SMA patients but there is a strong hint that there is an increased risk of bleeding and of kidney toxicity. In terms of efficacy the available clinical data so far gives an advantage to Zolgensma® where 75% of the 12 patients in the phase I trial, were able to sit without support at 24 months and 2 patients were able to stand and walk unassisted. In the ongoing phase III trial 47,6% of patients were able to sit by themselves and 13 of 19 survived without ventilation for 14 months. With Spinraza, similar to Zolgensma®, 23% of patients died and only 40% responded to treatment. This is however much better than placebo at 0% overall.
Novartis has “established readiness ahead of the US approval” with 60 medical centers on board to send blood for genetic manipulation and then deliver the re-engineered product and claims to be already in a position to reach 80% of US infants with SMA. As for manufacturing Novartis indicated that it had more than 1 million square feet of manufacturing being prepared to ramp up.
Access of Zolgensma® to European and Asian patients is at the top of Novartis as well as SMA Europe’s agenda. All over the world the same question will however be raised “who is going to pay for it”.
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