Gene therapy is an emerging field of drug development. From large-cap pharma to tiny biotechs, many companies are trying to make a name for themselves in gene therapy — a novel approach to treating or preventing diseases using genes.

Spark Therapeutics Inc (NASDAQ:ONCE)'s Luxturna is the only FDA-approved proper gene therapy and is indicated to treat adults and children with inherited retinal disorder that could lead to vision loss.

Novartis AG (NYSE:NVS)'s Kymriah and Gilead Sciences, Inc (NASDAQ:GILD)'s Yescarta, though mentioned as gene therapy products, are in fact cell therapy products that use the body's own T-cells to fight cancer.

The excitement is building, as the FDA is set to give its verdict on a second gene therapy product sponsored by Novartis. Zolgensma is being evaluated for spinal muscular atrophy — or SMA — Type 1. The Type 1 subtype affects infants from birth to six months of age.

The Product

Zolgensma came into the Novartis stable through its acquisition of gene therapy company AveXis and was previously known as AVXS-101. It has the shell of a genetically engineered AAV 9  virus, which acts as a vector or carrier of a normal copy of the SMN1 gene to the target motor neurons.

It has received both Breakthrough Therapy Designation and Priority Review status.

See Also: Attention Biotech Investors: Mark Your Calendar For These May PDUFA Dates

The Indication

SMA is a neuromuscular disease arising from a loss of motor neurons, leading to progressive muscle weakness and paralysis. The causal factor is a genetic defect in the SMN1 gene, which codes SMN — a protein essential for the survival of motor neurons.

SMA Type 1 is the most severe form of the genetic disorder, which is often lethal.

"The incidence of SMA is approximately one in 10,000 live births and is the leading genetic cause of infant mortality," according to Novartis. 

How Zolgensma Works

Zolgensma is delivered as a single, one-time infusion and works by replacing the missing or defective SMN1 gene with a functional copy that makes the SMN protein, which helps improve motor-neuro function and survival.

Development And Regulatory Pathway

Novartis announced FDA acceptance of its Zolgensma BLA Dec. 3, 2018. The PDUFA date is set for May.

Interim results from a Phase 3 study dubbed STRIVE presented at the 2019 Muscular Dystrophy Association Clinical and Scientific Conference in Orlando, Florida in mid-April showed that as of September, 21 of the 22 patients were alive and event-free.

The median age was 9.5 months, with six of the seven patients who could have achieved 10.5 months of age or older surviving event-free.

Natural history, however, indicates that 50 percent of the babies with SMA Type 1 will not survive or will require permanent ventilation by the time they reach 10.5 months of age.

Ahead of the trial, the gene therapy candidate was evaluated in a pivotal Phase 1 trial called START. The results from the study that evaluated both safety and efficacy showed that all 15 patients infused with Zolgensma were alive and without the need for permanent ventilation at 24 months.

This is commendable when considering that more than 90 percent of untreated patients with SMA Type 1 will die or require permanent ventilation by 24 months of age.

Incidentally, AveXis recently announced plans to expand a manufacturing facility in North Carolina and the acquisition of a manufacturing facility in Colorado to augment production capacity ahead of the planned launch of Zolgensma.

Competition

Zolgensma is not without competition, as Biogen Inc (NASDAQ:BIIB) has a SMA drug in Spinraza, which was approved in December 2016. Spinraza, the first approved medication for SMA of any subtype, was developed in collaboration with Ionis Pharmaceuticals Inc (NASDAQ:IONS).

Spinraza is priced at $750,000 for the first year and $375,00 per year subsequently.

Spinraza is to be administered intrathecally — administered via injection into the spinal cord or the subarachnoid space — every four months. Biogen's recently released first-quarter results revealed a slowdown in Spinraza patient starts in the U.S.

Roche Holdings AG Basel ADR (OTC:RHHBY) has a late-stage asset in risdiplam. If approved, it could be the first oral treatment for SMA. Risdiplam could be commercially available in 2021.

Zolgensma, if approved, could turn out to be a costly option, priced in the range of $4 million to $5 million, according to BioProcess International, which quoted AveXis President Dave Lennon in a February story.

An AveXis spokeswoman told Benzinga Thursday that the price of the treatment has not yet been established. 

"We are working closely with payers on creative options to ensure access, including installment payment plans, as well as outcomes-based arrangements, conducted through a third-party."

Novartis is also evaluating Zolgensma as an intrathecal formulation in a trial dubbed STRONG for SMA Type 2, which is a less severe form of SMA.

Safety Scare

The death of one of the 22 patients enrolled in the STRIVE study recently created a furor, but an independent safety board ruled that it was unrelated to the treatment.

Novartis is scheduled to make presentations on its START, STRIVE and STRONG studies at the American Academy of Neurology meeting in Philadelphia May 4-10.

Now all eyes are on the FDA's take on the drug and its approvability. Stay tuned to see whether Novartis climbs or stumbles at the FDA hurdle.