Go or no go? Esperion's double whammy and a look to priority reviews

Four assets with previous rejections are due FDA decisions in February, while those with priority review could become the next string of early approvals.

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The FDA’s run of early approvals continued in the first month of 2020, though this time it was only two – Horizon’s Tepezza and Blueprint’s Ayvakit – that received an early nod.

The latter gained the green light in patients with gastrointestinal stromal tumours driven by a specific mutation. The bigger indication will be fourth-line GIST, where Ayvakit has a February PDUFA date. However, this application is to be supported by results from the Voyager study, pitting Ayvakit against Stivarga, and since these data are not expected until the second quarter an FDA decision will likely be delayed.

Esperion’s bempedoic acid, another high-profile project, has two PDUFA decisions next month, one as a monotherapy and the other as a fixed-dose combination with Zetia. The cholesterol-lowering pill, used as an add-on to statins, has a good chance of receiving regulatory approval thanks to its positive pivotal programme, while the lack of an advisory committee could also be a good sign.

The real question will be the commercial opportunity. The lipid-lowering market is incredibly competitive and bempedoic acid could get an important boost if its cardiovascular outcomes study, Clear outcomes, proves successful; the trial has a primary completion date at the end of 2021.

Heads up

The anti-CGRP migraine market looks like it will become even more crowded next month, with a regulatory decision for eptinezumab in the prevention setting. The three products already on the market, Aimovig, Emgality and Ajovy, can all be administered subcutaneously once a month; the last can also be given quarterly. Eptinezumab is dosed every quarter via a 30-minute intravenous infusion. Lundbeck gained the MAb through its $2bn acquisition of Alder last September.

Staying with migraine, Biohaven’s Zydis ODT, a fast-acting formulation of the oral CGRP rimegepant, has a decision in the first quarter in an acute setting. Biohaven’s offering will have to battle it out with Allergan’s Ubrelvy; this became the first approved oral CGRP antagonist at the end of last year.

Notable first-time US approval decisions due in February
Project Company PDUFA date Product NPV ($m)*
Twirla Agile Therapeutics Feb 16 87
Intravenous meloxicam Baudax Bio Feb 20 -
Eptinezumab Lundbeck Feb 21 1,443
Bempedoic acid monotherapy and Zetia combo Esperion Feb 21 and Feb 26 respectively 2,039
Barhemsys Acacia Feb 26 53
Ayvakit Blueprint Feb 14 (expected to be extended due to Voyager data) 3,465
Taclantis Sun Pharma Advanced Research Estimated Feb 28 -
Zydis ODT Biohaven Q1 1,633 (rimegepant franchise)
Posimir Durect Likely Q1/Q2 380
*NPV data as of January 24. Sources: EvaluatePharma, company releases.

Four assets due a decision in February have been rejected at least once before. Durect’s painkiller Posimir was first rejected back in 2014, but finally got in front of an FDA advisory committee earlier this month. The outcome of the meeting, however, was far from unanimous, with six for and six against approval. A final PDUFA date has not been disclosed, but is expected in the first half of the year.

Another pain product, Baudax Bio’s intravenous formulation of meloxicam, has been rejected twice by the agency. An oral version called Mobic has been on the market since the 1990s, but Baudax says its intravenous version acts faster; however, the most recent complete response letter for this project, which was successfully appealed, specifically stated that the IV version had a delayed onset of analgesia. Baudax was spun out of Recro Pharma at the end of 2019.

Agile’s contraceptive patch Twirla also had two previous rejections, the first seven years ago. Nevertheless, it gained a positive panel verdict last October that caused the group's shares to rocket 223%. The committee voted 14-1 that the benefits of the project outweighed its risks, but questions remained over Twirla’s efficacy and doubts were raised about whether the project is a low-dose, and therefore potentially safer contraceptive, as Agile has claimed.

Acacia’s Barhemsys, indicated for patients who develop post-operative nausea and vomiting, also had two prior rejections. Both setbacks were due to deficiencies with the contract manufacturer for Barhemsys’s active ingredient, amisulpride. The company’s shares dropped 57% when news of the second CRL was announced last May, but have been gaining ground since December. Acacia now has a new supplier for amisulpride.

Supplementary and other notable approval decisions due in February
Product Company Event type Date
Keytruda Merck & Co sBLA to update the dosing frequency for to include an every-six-weeks dosing for melanoma and multiple other indications Feb 18
Vesicare Astellas sNDA for neurogenic detrusor overactivity in paediatric patients Estimated Q1
Source: EvaluatePharma company releases.

Priority pass

Lastly, with the FDA seemingly on an approval rally, Vantage looked at upcoming decisions that have priority review attached and could come early. First up is Zogenix’s Fintepla in Dravet syndrome, a rare form of epilepsy that begins in childhood. GW Pharma’s Epidiolex gained approval in this indication in 2018. And in April an FDA panel will discuss the use of Intercept’s Ocaliva in Nash; a decision is pegged for June.

Upcoming first-time US approval decisions with priority review
Product Company Indication PDUFA date Product NPV ($m)*
Fintepla Zogenix Dravet syndrome Mar 25 591
UGN-101 (mitomycin gel) Urogen Low-grade upper tract urothelial cancer Apr 18 86
Selumetinib Astrazeneca/Merck Paediatric patients with NF1 plexiform neurofibromas Q2 192
Risdiplam PTC/Roche Spinal muscular atrophy (Firefish, Sunfish) May 24 5,260
Belantamab mafodotin GSK Relapsed or refractory multiple myeloma (Dreamm-2) Estimated July 21 3,820
Selpercatinib Lilly Ret-altered lung and thyroid cancers (Libretto-001) Q3 4,065
*NPV data as of January 24. Source: EvaluatePharma, company releases.

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