While the FDA approved Zogenix Inc.’s Fintepla (fenfluramine), an oral treatment for patients ages 2 and older with seizures associated with Dravet syndrome, a rare, pediatric-onset form of epilepsy, the company stock continued its months-long struggle.

The company’s shares (NASDAQ:ZGNX) closed down 9.42% at $25.47 June 26, the day after Fintepla’s approval late on its June 25 PDUFA date.

SVB Leerink’s Marc Goodman Given wrote Thursday that “the FDA delayed approval two previous times, there has been investor skepticism regarding this approval, so we would expect the stock to move nicely tomorrow into the $35-40 range.”

Year to date, Zogenix stock is down 51.3%, with a huge fall-off occurring Feb. 7 as shares went for $52.62 each when the market opened and closed at $32.12.

Fintepla, whose journey began six years ago in Belgium, will launch by the end of July through the Fintepla risk evaluation and mitigation strategy (REMS) program, where Dravet syndrome patients will be monitored while being treated. The warning label notes Fintepla is associated with valvular heart disease and pulmonary hypertension, so patients are required to have echocardiograms before treatment, every six months during treatment and once three to six months after a discontinued treatment.

Ashish Sagrolikar, executive vice president and chief commercial officer, Zogenix

The price will vary from patient to patient, Ashish Sagrolikar, Zogenix’s executive vice president and chief commercial officer, said in Friday morning’s conference call, with an average list price based on dosing and patient weight expected to be $96,000 per year. The company will have a patient assistance program offering support based on patient needs, he added.

Dravet syndrome, which afflicts children, is life threatening, chronic and the seizures associated with it are severe. It also comes with an increased risk of sudden unexpected death.

There are anywhere from 6,000 to 8,000 Dravet syndrome patients in the U.S.

SVB Leerink analyst Marc Goodman on March 3 estimated Fintepla’s U.S. sales in Dravet syndrome to about $22 million in 2020 and about $83 million in 2021.

Fintepla’s approval was based on two randomized, double-blinded, placebo-controlled phase III studies, along with safety data from an open-label extension trial that lasted up to three years for some of the studies’ 341 patients. Patients ages 2 to 18 receiving the treatment had significantly fewer convulsive seizures than those receiving placebo. The seizures were held at bay within the first three to four weeks and stayed that way for the 14- to 15-week treatments.

Its path to approval wasn’t smooth. In April 2019, the FDA sent Zogenix a refusal to file letter, complaining the firm failed to include nonclinical data related to Fintepla’s chronic use and that the NDA contained the wrong version of the clinical dataset on the package, which meant the regulators couldn’t complete the review until they had more information.

With Fintepla, gatekeepers said they wanted sensitivity analyses on phase III results.

“The data are incredibly robust to any sensitivity analysis we have conducted, to the point where we're not seeing any shift in ‘p’ values and very, very small differences in endpoint estimates,” CEO Stephen Farr told investors on the March 2 earnings call. “We don't think there's really anything that the FDA is going to uncover here that we have not already seen.”

Fintepla is the small molecule formerly known as ZX-008. Fenfluramine is a serotonin reuptake blocker.

As half of the weight-loss drug known as fen-phen, fenfluramine’s past is checkered. It was withdrawn from the market in 1997 after cases of heart valve defects and pulmonary hypertension were reported in people who had taken the compound with phentermine.

On Feb. 6, the company released phase III top-line results from its study of Fintepla for treating Lennox-Gastaut syndrome (LGS). The trial met its primary objective of demonstrating that Fintepla – known to have serotonergic effects while targeting the sigma-1 receptor – was, when given at a dose of 0.7 mg/kg/day, superior to placebo in reducing the frequency of drop seizures in LGS, based on the change between baseline and the titration and maintenance treatment period (p=0.0012). But investors apparently wanted even better efficacy.

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