Why is Zolgensma so expensive?

Zolgensma is a one-time-only gene therapy treatment for children aged less than two years with spinal muscular atrophy (SMA) that costs $2.1 million for the single treatment. The reason Zolgensma is so expensive is because that is the price Novartis has decided it is worth because it “dramatically transforms the lives of families affected by this devastating disease” and the claimed cost of bringing new drugs to market. But this price is not without controversy.

For a start, the early development of Zolgensma was financed by the National Institutes of Health and several charities devoted to finding treatments for SMA, including many U.S. charities such as Sophia’s Cure, Cure SMA, Getty Owl Foundation, Fighting SMA, Jadon’s Hope Foundation, the Gwendolyn Strong Foundation, and Miracle for Madison. Many of these charities use donations by patient families and friends to subsidize research and clinical trials into new medicines for SMA.

The CEO of Novartis, Vas Narasimhan, argues that gene therapies represent a medical breakthrough in the way that they offer hope of a cure for deadly genetic diseases with a single dose. In some cases, the alternative is a multi-dose treatment with incremental improvements. For example, an alternative to Zolgensma is Spinraza that is taken four times a year for life. The list price is $750,000 for the first year and then $350,000 per year after that, so about $4 million a decade.

But how do they calculate the actual cost? Many companies use a value-based pricing model which calculates the cost based on how many years of life gained as well as taking into account the effectiveness of the drug. But this means putting a price on how much a life is worth, as well as ensuring the company makes a reasonable margin on their investment. Little is disclosed about the true cost of bringing a new drug to market, and Novartis didn’t develop Zolgensma but acquired it through the $8.7 billion purchase of US firm AveXis.

Most health insurance systems do not allow for one-time treatments at such a price and a big price tag is also no guarantee that a drug will meet all expectations. Novartis will allow payments over five years, at $425,000 per year, and has said it will give partial rebates if the treatment doesn’t work.

How does Zolgensma work?

Zolgensma (onasemnogene abeparvovec-xioi) treats the genetic root cause of SMA by replacing the missing or nonworking SMN1 gene with a new, working copy of a human SMN gene. It does this by using a vector, which is a “carrier” that can get the new, working SMN1 gene into the body. The vector in this case is a virus called AAV9 that has had its DNA removed and replaced with the SMN1 gene. This type of virus does not make you sick but can quickly travel through the body to the motor neuron cells and deliver the new gene.

Zolgensma sits inside the nucleus of the motor neuron cell and tells the motor neuron cell to start making new SMN1 protein. Once the genes reach their destination, the vectors are broken down and excreted from the body and do not become part of the child’s DNA.

How effective is Zolgensma?

Results from an open-label, single-arm clinical trial that enrolled 21 children (range of ages 0.5 to 5.9 months) who all received 1.1 x 10¹⁴ VG/kg Zolgensma reported:

• 13 of the 19 patients continuing in the trial reached at least 14 months of age without permanent ventilation, at the March 2019 data cut off
• 10 of the 21 patients (47.6%) achieved the ability to sit without support for ≥ 30 seconds between 9.2 and 16.9 months of age (mean age was 12.1 months). This was significant because based on study entry criteria none of these patients would have been expected to attain the ability to sit without support, and only approximately 25% of these patients would be expected to survive (being alive without permanent ventilation) beyond 14 months of age
• 16 of the 19 patients had not required daily non-invasive ventilator use.