By Denise Roland
Isaac Olthoff, 10 months old, lacks a gene crucial for muscle control. He can't sit up and may never be able to stand independently.
A cutting-edge treatment that could prevent his disease from worsening went on sale in May. But at $2.1 million a patient, Zolgensma is the world's most expensive drug and his insurer has refused to pay for the gene therapy.
The treatment for spinal muscular atrophy, or SMA, is posing a dilemma for insurers: it promises to halt the progressive disease in one dose but isn't yet proven to work in all cases. That uncertainty is making some wary of parting with such a steep sum.
That is bad news for patients looking for a cure and for Zolgensma-maker Novartis AG, which hopes the drug will generate billions of dollars in sales. It also underscores the challenge facing a slew of other drugmakers planning to launch gene therapies in the coming years, which will also likely come to market with big price tags and limited trial data.
Such therapies provide a working copy of a defective gene, potentially curing diseases that are rare and difficult to treat in one shot. That promise means the Food and Drug Administration is often willing to accept small clinical trials to speed up the development process.
For Zolgensma, the two main sticking points for insurers are age and the severity of disease. The only clinical-trial evidence so far is limited to children aged six months and under with the most severe form of the disease. Novartis is still testing the treatment in older children with less severe SMA.
Zolgensma works by providing a working version of a gene called SMN1 that is crucial for muscle control. Babies with SMA lack that gene, but have varying levels of a backup gene. Those with just one or two copies of the backup gene show symptoms of SMA very young and have the most severe disease. The more copies of the backup gene they have, the later their symptoms kick in and the less severe the disease.
Isaac's insurer, Aetna Inc., restricts Zolgensma to babies under nine months of age with the most severe form of SMA. A spokesman said in an email that criteria was "based on the most recent published science, which we continuously evaluate."
Instead, it has agreed to pay for another treatment called Spinraza that works by strengthening the backup gene. But Isaac's mother Michelle said she would much prefer Zolgensma because it involves just a single infusion. Spinraza is given every four months over the lifetime of the patient.
Mrs. Olthoff, who lives in Colombia, Mo., said she was surprised because the FDA in May gave its blessing for Zolgensma to be used in children up to two years old, regardless of severity.
"There is a legitimate issue that the FDA's label exceeds the population studied," said Michael Sherman, chief medical officer at insurer Harvard Pilgrim Healthcare, which is still deciding its coverage policy for Zolgensma. He said it was likely that insurers would expand their coverage as more evidence became available.
An FDA spokeswoman said the approval was based on the "compelling evidence" in younger babies with the most severe form, adding that the underlying cause is the same for all types of SMA.
Isaac isn't alone. Jackson Schultheis in Evansville, Ind., 18 months, was denied Zolgensma on the basis of age. Tora Patgiri in Columbus, Ohio, also 10 months old, got the treatment only on appeal. All three also have a less severe form of SMA than the trial babies.
Maisie Forrest in Grand Junction, Colo., 19 months old, has the most severe form and was initially deemed too old for the treatment. MaKenzie Burleson in Hammond, La., who turns 2 in September, also has the most severe form of SMA and was initially turned down because her condition is worse than that of the clinical trial babies. Both got Zolgensma after their families appealed. The insurance for 3-month-old Duke Stanger of Monroe, Ohio, doesn't cover gene therapies.
"At the end of the day this is about the price," said Sanford C. Bernstein & Co. analyst Ronny Gal, who found that so far nearly half of the top 30 insurers have committed to covering Zolgensma, though most have placed restrictions on their policies based on age or severity of disease. He said the drug isn't getting the benefit of the doubt for the "very likely scenario" that it works in older patients.
Novartis has defended the drug's $2.1 million price tag partly on the grounds that it costs less than Spinraza in the long term. The competing drug, a multidose treatment made by Biogen Inc., costs $750,000 for the first year and then $375,000 for each year after that.
To allay concerns over the cost, Novartis is offering insurers the option to pay for the treatment in equal annual installments over five years and has pledged to issue partial refunds if the treatment doesn't work.
Chief Executive Vas Narasimhan said on a recent call with reporters that insurers on the whole were proving willing to pay for Zolgensma, adding that so far plans covering 40% of Americans had agreed to provide it. But he said Novartis was aware of some refusals for patients with less severe forms of the disease. "That's something we're going to have to work through," he said.
Write to Denise Roland at [email protected]