Zogenix Risks Fintepla Uptake With Dravet Drug’s High Price
Executive Summary
The average list price of $96,000 per year is three times the cost of GW’s competing drug Epidiolex, but Zogenix is betting that the reduction in seizures seen in clinical trials will justify the expense.
Zogenix Inc. won US Food and Drug Administration approval for Fintepla (fenfluramine) in the treatment of Dravet syndrome, a rare form of epilepsy that patients begin to experience in infancy, but set a list price that is three times the cost of another relatively new drug for the disease, raising questions about whether the price will limit uptake.
The US FDA approved Fintepla on 25 June for the treatment of seizures associated with Dravet syndrome in patients age 2 and older – a broader population than the 2- to 18-year-old patients enrolled in Zogenix’s clinical trials. The company plans to launch the drug through a specialty pharmacy in late July.
As expected, given the severe side effects seen with the combination of fenfluramine and phentermine (fen-phen) when taken by adults for weight loss, the Fintepla label includes a black box warning about the potential for valvular heart disease and pulmonary arterial hypertension.
While neither adverse event was observed in Zogenix’s clinical trials, the risk evaluation and mitigation strategy (REMS) for Fintepla requires patients to receive an echocardiogram before treatment is initiated with the drug, every six months while on therapy and within three to six months of stopping treatment. Prescribers, pharmacies and patients must be certified under the REMS program.
Fintepla approval came after two regulatory delays. First, the FDA issued a refuse-to-file letter in April 2019 due to missing non-clinical data and inaccurate clinical trial information in the new drug application. (Also see "US FDA Filing Mistake For Fintepla Dents Zogenix" - Scrip, 9 Apr, 2019.) Then after resubmission of the NDA the FDA extended the action date by three months from the prior 25 March PDUFA date upon submission of new information from Zogenix. (Also see "March Madness: Upcoming US FDA Decision Dates To Watch" - Pink Sheet, 1 Mar, 2020.)
“We believe we’ve priced the drug fairly with respect to the benefit it will provide to Dravet patients." – Zogenix president and CEO Stephen Farr
However, while the FDA approved Fintepla on the NDA’s revised action date, investors were concerned about the REMS requirements and the list price for Fintepla relative to GW Pharmaceuticals PLC’s Epidiolex (cannabidiol), which was approved for Dravet syndrome and Lennox-Gastaut syndrome (LGS) two years ago. (Also see "GW's Epidiolex Approval Encouraging For Pharma-grade Cannabinoid Pipeline" - Scrip, 29 Jun, 2018.) Biocodex's Diacomit (stiripentol) is also approved for Dravet syndrome in patients aged 2 and older, but as an add-on clobazam.
Fintepla approval was announced after the stock market closed on 25 June and Zogenix traded lower on 26 June, closing down 9.4% at $25.47 per share, after chief commercial officer Ashish Sagrolikar revealed the drug’s list price of $1,278 per 30mL bottle during a conference call with investors and analysts.
CEO Says Price Reflects Drug’s Benefits
Annual pricing will vary for each patient, since dosing is weight-based, but given the average weight of about 35kg for patients in Zogenix’s clinical trials, the average list price is $96,000 per year. Analysts noted that the list price for Epidiolex is about $33,000 per year.
“We believe we’ve priced the drug fairly with respect to the benefit it will provide to Dravet patients,” Zogenix president and CEO Stephen Farr said in an interview. “I just want to emphasize here that Dravet syndrome is a rare disease; it's a small patient population with an urgent need for effective new treatment options. This is not an anti-epileptic drug that has an indication beyond Dravet syndrome, so we think that it’s been appropriately priced based upon the potential therapeutic benefit and the fact that it's going to be indicated in a rare disease.”
Fintepla met primary and secondary endpoints in a Phase III clinical trial earlier this year in LGS – the other seizure disorder where GW Pharma’s Epidiolex is approved. Zogenix will meet with the FDA in the second half of 2020 to determine what additional information the agency will require to approve Fintepla for LGS, but Farr told Scrip that the company has not determined yet whether it will launch the drug in the larger indication at a different price.
About 550 Dravet patients are being treated with Fintepla at no cost through an expanded access program and Zogenix’s open-label extension trials, and the company intends to transition those patients to paid prescriptions when the drug launches commercially in late July. However, analysts questioned whether those and other patients would opt to take Epidiolex or generic medicines first before paying Fintepla’s relatively high cost.
‘Sticker Shock’ Could Limit Uptake
“We anticipate the switch from OLE and EAP to having to pay a co-pay for Fintepla will be a sticker shock to many patients and is likely to see many patients move to lower cost drugs like Epidiolex prior to trying Fintepla,” Ladenburg Thalmann Michael Higgins said in a 26 June note.
Needham analyst Serge Belanger commented in a same-day report that Fintepla’s higher price than Epidiolex’s cost may be a bigger issue for payers in LGS where the Zogenix drug’s efficacy in Phase III was “mostly equivalent” to GW Pharma’s drug.
“While we believe Fintepla's unprecedented efficacy in [Dravet syndrome (DS)] patients merits premium pricing, the high price tag likely means the product will mostly see usage in patients who continue to be refractory despite Epidiolex use, which may be as high as 25%-50% of DS patients,” Belanger wrote. “This still represents a significant treatment role and market opportunity for Fintepla.”
William Blair analyst Tim Lugo forecast peak sales of Fintepla in DS of about $470m, noting that Epidiolex generated about $300m in 2019 sales based on the unmet need in both DS and LGS.
“However, while we believe the success of Epidiolex validates the significant unmet need in the indication and we believe Fintepla holds a best-in-class profile, we expect a slower uptake for Fintepla given the higher price, single indication (Epidiolex launched in LGS and DS concurrently), black-box warning and REMS program,” Lugo wrote.
Zogenix has established a program called Zogenix Central to provide comprehensive support services to Dravet syndrome patients and families, including help with the REMS program requirements, finding a local echocardiogram center, securing reimbursement, and seeking co-pay assistance from the company for the drug and the required ECGs.
Launch Will Be Virtual/In-Person Hybrid
The Fintepla launch will include a combination of virtual meetings with prescribers using online tools and office visits with doctors in locations where social distancing requirements due to COVID-19 have been eased enough to allow for in-person meetings.
Zogenix will target the 450-500 treatment centers recognized in the US for their expertise in treating epilepsies, which treat about 80% of Dravet syndrome patients. The company said its sales representatives have decades of experience marketing products to doctors who treat epilepsies, including rare seizure disorders.
Farr noted that the commercial team will start by making doctors aware of Dravet syndrome and Fintepla as a new and effective treatment. The sales reps will target prescribers who are aware of the disease and the drug, including doctors who participated in Fintepla clinical trials, and extend their marketing to those who may never have diagnosed the disease.
Discussions with payers regarding reimbursement are ongoing, but Zogenix is confident about obtaining coverage for Fintepla.
“Payers have been impressed with the clinical efficacy that we have generated in our Phase III trials with respect to the rapidity of the seizure control, the extent of seizure control as well as the ability to control seizures over long periods of time,” Farr said. “That has really been well received by payers, because they see how control of seizures could also really reduce overall costs of this severe disease.”
Zogenix’s commercial chief Sagrolikar said during the company’s conference call that “we balanced these seizure reduction benefits with our commitment to ensure access for all patients in a reasonable timeframe and at affordable levels. Our conversations with payers indicate that based on Fintepla’s clinical profile established in our clinical trials we should be able to achieve broad access for Fintepla."
Farr explained during the conference call that Dravet syndrome “is a rare and severe form of intractable epilepsy that typically begins in infancy. Dravet patients incur frequent and/or prolonged seizures that can lead to a number of debilitating comorbidities including behavioral, cognitive and development delays. Our research suggests there are between 6,000 and 8,000 Dravet patients in the United States.”
Many of those patients have poor seizure control despite the availability of other anti-epileptic drugs. “Effective therapies that provide profound and durable seizure reductions in this patient population can fulfill significant and remaining unmet need,” Farr said.
Needham analyst Belanger opined in a 25 June note that the cardiotoxicity historically associated with higher doses of fenfluramine in adults are not likely to prevent doctors from prescribing Fintepla, because of the efficacy observed with the drug in Dravet syndrome patients who did not adequately respond to available treatments – and because the more than 4,400 ECGs conducted during Zogenix’s clinical trials uncovered no serious adverse effects.
“While Fintepla is the third FDA-approved DS therapy (after Epidiolex and Diacomit) to reach the market since 2018, it should be a welcome addition to the treatment armamentarium given its unprecedented efficacy levels in reducing seizure frequency,” Belanger wrote. (Also see "Dravet Syndrome: A Rare Epilepsy, Now With Two Approved Treatments" - Scrip, 24 Aug, 2018.)