H. Lundbeck A/S’ antibody-based migraine therapy, Vyepti (eptinezumab-jjmr), which just received FDA approval as the first and only intravenous preventive treatment for adults, enters a market forecast to grow to $7 billion by 2027. While some analysts placed Vyepti’s earnings potential at about $800 million annually, the drug itself is positioned to become a possible blockbuster, earning $1 billion annually.

Vyepti is the fourth antibody targeting calcitonin gene-related peptide (CGRP) to reach the market and comes with an unconventional dosing schedule: infused 30 minutes every three months while the other currently approved antibodies are subcutaneously administered. The recommended dosage is 100 mg every three months.

The approval follows last fall’s acquisition of Alder Biopharmaceuticals Inc. by Lundbeck for up to $1.95 billion net of cash, which came with Alder’s lead drug candidate, eptinezumab. The deal was touted by Lundbeck at the time as “the biggest deal ever done by a Danish pharmaceuticals company.”

Vyepti becomes available in April. While the price was not revealed, SVB Leerink’s Marc Goodman expects annual costs of between $3,000 to $5,000. Last fall, J.P. Morgan analysts forecast peak sales of about $800 million in migraine prevention for eptinezumab. Lundbeck has not issued any sales forecasts, but its ambitions go beyond that estimate to blockbuster status. Goodman expects peak sales of $700 million annually in the U.S.

Jefferies analysts Peter Welford, Colin White, Philippa Gardner and Lucy Codrington wrote that being the fourth anti-CGRP to market could be challenging, citing the “less convenient I.V. administration vs. competitor subcutaneous, and oral anti-CGRPs on the horizon, which could intensify competition.”

The Jefferies group assumed a moderate market penetration and niche use in hospitalized patients and CGRP failure while forecasting $600 million worldwide peak sales.

A potential competitor, also a possible blockbuster, is Biohaven Pharmaceutical Holding Co. Ltd.’s rimegepant, which is up for FDA review this quarter. Rimegepant is one of 11 candidates on the Cortellis Drug to Watch list, which showcases drugs entering the market this year with the potential to hit annual sales of $1 billion each within the next five years.

Rimegepant’s NDA, using a priority review voucher, was filed in the U.S. in the second quarter of 2019 seeking approval to treat acute migraine. Worldwide rights were acquired by Biohaven in 2016 from Bristol-Myers Squibb Co. If approved, sales are expected to rise to $1.03 billion in 2024, according to Cortellis analysis, although rimegepant would compete with Ubrelvy (ubrogepant, Allergan plc) and orals from other classes, such as the 5-HT 1f agonist Reyvow (lasmiditan, Eli Lilly and Co.), approved by the FDA in October 2019. Other potential competitors include Trokendi XR (topiramate, Supernus Pharmaceuticals Inc.) and Botox (botulinum toxin type A, Allergan plc).

Mizhuo Securities analyst Vamil Divan said he sees rimegepant’s best future in treating acute migraine, given the market’s increasing size and what it termed “a less-competitive environment than what now exists” in migraine prevention. Divan wrote that a conservative sales estimate in migraine prevention for rimegepant runs at around $360 million by 2030 because of competition not only by Vyepti but also from Botox, Aimovig (erenumab-aooe, Amgen Inc./Novartis AG), Emgality (galcanezumab, Eli Lilly and Co.) and Ajovy (fremanezumab, Teva Pharmaceuticals Co. Ltd.). Divan expects “rimegepant to deliver a placebo-adjusted reduction of at least one headache day per month, which we believe would be competitive with other agents … and differentiate the drug in being able to be used for both migraine prevention and acute treatment.”

Vyepti’s approval stems from two phase III studies, PROMISE-1 for treating episodic migraine and PROMISE-2 for chronic migraine. Both trials hit their respective primary endpoints, a decrease in the mean monthly migraine days (MMD) over months one through three. Both studies also showed sustained reductions of mean MMD through the second dose, in month six. The program found a treatment benefit over placebo as early as day one following the infusion. The percentage of patients with migraine was lower than the placebo group for the majority of the first seven days following treatment.

Patients in both studies were randomized to receive placebo, Vyepti 100 mg or Vyepti 300 mg. Patients could use concurrent acute migraine or headache medications, including migraine-specific medications such as triptans, ergotamine derivatives, during the trial.

Vyepti was approved on its target PDUFA date, Feb. 21. The company stock, traded on the Copenhagen Stock Exchange (LUN), drifted 4.8% lower on Monday amid a market that was drenched in red. 

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