A rare genetic disorder which limits an infant’s lifespan to just 24 months could be cured with a groundbreaking new gene therapy approved by the US Food and Drug Administration but at over US$2 million per dose, it could well be out of the financial reach of families who need it the most.
Swiss pharmaceutical company Novartis received US government approval this week for Zolgensma which alters the underlying genetic cause of Type 1 spinal muscular atrophy (or SMA) and could permanently stop progression of the disease.
It has been developed as a one-time intravenous infusion and approved for paediatric SMA patients under the age of two including those yet to show symptoms.
But it has been priced at a record US$2.125m – or US$425,000 per year over five years for insurance companies – making it the most expensive drug in history and kickstarting a debate which some claim puts a question mark over the real cost of so-called ‘super drugs’.
Novartis executives have defended the price and said it would be working with health insurers to implement pay-over-time and outcomes-based agreements to accelerate patient access and reimbursement for the drug.
In return, it would ask insurers to promise to provide a quick decision on whether or not a child will qualify for treatment.
The company also claimed the price tag to be “highly cost effective” and “fair and reasonable” given the benefits demonstrated in clinical trials and the value compared to expensive long-term SMA treatments on the market – such as the anti-sense oligonucleotide Spinraza infused into the spinal canal every four months – which can cost several hundred thousand dollars a year.
Developed by Ionis Pharmaceuticals and Biogen, Spinraza received FDA approval in 2016 to treat but not cure SMA, with prices ranging from US$750,000 in the first year of treatment to $375,000 per year thereafter.
A decade of treatment with Spinraza could cost well over US$4m.
Despite the steep investment, sales of Spinraza were clocked at around $US1.7 billion last year and are expected to hit $US2.2 billion in 2022.
Spinal muscular atrophy affects motor neurons – the nerve cells which control muscle contraction – of the spinal cord and is the leading genetic cause of infant mortality, affecting one in every 10,000 live births.
The most severe Type 1 form of the disease often leads to paralysis, impaired breathing and death by 24 months.
The condition is caused by a mutation in the SMN1 gene, which prevents the gene from manufacturing the functional SMN protein that motor neurons need to survive.
Zolgensma uses a re-engineered virus to deliver a fully-functional copy of the defective gene so that SMN protein can be produced.
The FDA approved the drug based on an ongoing clinical trial involving 36 patients with SMA aged from two weeks to eight months.
Those treated with Zolgensma showed significant improvement in their ability to achieve developmental motor milestones such as head control and being able to sit up without support.
Results to date show the effects of the treatment have not waned, with some patients already approaching their fifth birthdays.
Novartis said there are about 400 new infant patients a year in the US, or about 30 a month, who would qualify for treatment with Zolgensma.
In addition, 700 patients who already have the disease would be eligible.
Novartis plans to implement patient support and payment programs and does not expect out-of-pocket costs to be prohibitive.
Complex genetic diseases such as SMA could one day be eliminated not via one-off infusions, but by using gene editing tools such as CRISPR-Cas9 to “edit out” mutations and cure diseases in vitro.
The scientific community worldwide is developing CRISPR-Cas9 mediated therapies for a wide range of conditions including inherited eye diseases, neuro-degenerative illnesses such as Alzheimer’s and Huntington’s disorders, and non-inherited diseases such as cancer and HIV.
Currently, most research is done to understand diseases using cells and animal models, with CRISPRing of human cells believed to still be years away.
In October, researchers from the University of Pennsylvania and the Children’s Hospital of Philadelphia took the first step toward curing genetic disease before birth via genome editing when they used CRISPR to alter the DNA of laboratory mice in the womb, eliminating an often-fatal liver disease before the animals had even been born.
The experiment confirmed the potential for science to one day cure human genetic diseases before birth.
“A lot more animal work needs to be done before we can even think about applying this [fetal genome editing] clinically,” said research head Dr William Peranteau.
“But I think fetal genome editing may be where fetal surgery [which is now routine] once was, and that one day we’ll use it to treat diseases which cause significant morbidity and mortality.”
In May, Australia’s Office of the Gene Technology Regulator decided to regulate CRISPR gene editing technology and approve it for plants, animals and human cell lines from October.