[Updated 4/10/2020, 3:24 p.m. See below.] Cameron Hewitt’s family celebrates the anniversary of her life not once, but twice yearly: Besides her September birthday, they commemorate a day in March—the anniversary of two-year-old Cameron receiving the gene therapy that gave her a new shot at life.
Cameron was born with spinal muscular atrophy (SMA), a genetic disorder that leads to the progressive loss of muscle function. In its most common and severe form, the disease leads to death within one or two years. The Hewitt family, which lives in Apex, NC, credits Zolgensma, a gene therapy approved by the FDA last year, as the reason Cameron lived to her second birthday and continues to improve today.
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FDA approval for the intravenously administered treatment covers SMA patients who, like Cameron when she enrolled in a clinical trial in 2018, are younger than 2. Zolgensma’s maker, Novartis (NYSE: [[ticker:NVS]]), wants approval to treat more SMA in patients of all ages. For that, more data are needed. Novartis is continuing to generate supporting data from additional clinical trials. Meanwhile, its subsidiary AveXis, which developed the treatment, is working to boost its capacity to produce Zolgensma and other gene therapies in its pipeline that are now being prepared for tests in humans. [Paragraph updated to clarify the scope of Zolgensma’s approval.]
MILESTONES MISSED
SMA stems from a defect in survival motor neuron gene 1 (SMN1), which is responsible for producing a protein needed for the health and proper function of motor neurons. The disease leads to muscle weakness that worsens with age. That muscle weakness isn’t necessarily apparent at birth. Cameron hit her initial development milestones, her father, Josh Hewitt, said at a launch event last month for AveXis’s Durham, NC, facility. But at 4 months old, Josh and Kimberly Hewitt, her mother, noticed Cameron appeared weaker and had more difficulty moving. SMA patients have difficulty sitting up, rolling over, or even lifting their heads. The rare condition is found in about 1 in every 11,000 births, according to patient group Cure SMA.
Cameron is one of an estimated 378 North Carolinians living with the disease. She was 5 months old when her diagnosis of SMA type 1, the most severe form of the disease, was confirmed. The Hewitts then learned their infant daughter had two treatment options. The first was nusinersen (Spinraza), a drug developed by Biogen (NYSE: [[ticker:BIIB]]) and Ionis Pharmaceuticals (NASDAQ: [[ticker:IONS]]) that in 2016 became the first FDA-approved SMA treatment. That drug, given as an injection into the spinal fluid, was developed to boost production of the functional SMA protein by targeting the SMN2 gene. Patients need that injection every four months for the rest of their lives. Unlike Zolgensma, Spinraza is approved for all SMA types in patients of any age.
The second option was the experimental AveXis gene therapy. It uses a modified virus to deliver genetic instructions into a patient’s cells, giving them the capability to produce the needed muscle protein—potentially for life. Though the AveXis treatment is meant to be given once, the long-term durability of its therapeutic effect is still unknown.
Novartis launched Zolgensma last June with a $2.1 million price tag before factoring in rebates or discounts. As a one-time treatment, the therapy is intended to avoid costly hospitalizations and other expenses that come with managing SMA. Its price falls on the upper end of the range the Institute for Clinical and Economic Review (ICER) calculates is cost effective for patients and the health system.
The watchdog group, a frequent critic of high drug prices, pointed to Zolgensma Phase 3 data (Cameron’s study) showing that 21 of the 22 patients who received the gene therapy were still alive. The lone patient death was deemed to be unrelated to the treatment. ICER says its price range assumes the US widely adopts newborn screening for SMA. In 2018, the US Department of Health and Human Services put SMA on the list of diseases it recommends states include in their newborn screening programs.
Since winning FDA approval, Zolgensma has made headway with insurers, gaining coverage for 97 percent of those who have private health insurance, Dave Lennon, AveXis’s president, told Xconomy in an interview. For those covered by Medicaid, that figure is 50 percent.
“No one jumps up and down and thanks of us for charging seven figures for a product,” Lennon says. “But at the same time, they understand the value proposition that it brings and they understand that the investment of $2 million now saves a lot of money down the road.”
Last year, 200 insured patients were treated with Zolgensma, Novartis reported in its 2019 financial results. The gene therapy generated $361 million in sales that year. Those figures are expected to grow as newborn screening reveals more babies with SMA.
PRECLINICAL PROBLEMS, PIPELINE PROGRESS
Zolgensma revenue will also grow if the therapy is approved for patients 2 and older who span a range of SMA types. Clinical trials are underway. But AveXis is also overcoming concerns about previous preclinical tests. Last August, the FDA reported that AveXis notified the agency that some of its submitted preclinical mouse data were “manipulated.” However, the regulator found no evidence that patient data were altered and said the gene therapy should remain on the market. AveXis fired those allegedly responsible for the data manipulation and integrated its quality controls with those of Novartis. Novartis CEO Vas Narasimhan said on conference call Monday that the FDA has closed its inquiry into this matter with no penalties imposed on the company.
But last October, Novartis announced a partial clinical hold on a Phase 1/2 study testing an intrathecal formulation of the gene therapy—an injection into the spinal fluid. This study is intended to support approval of the treatment for patients with SMA type 2. Lennon says a review of data in monkeys found
