Go or no go? The FDA plays hardball

April will see the US regulator examine Pfizer’s Jak in atopic dermatitis, and experts meet to discuss accelerated approvals in oncology.

Pfizer’s abrocitinib is forecast to become an important new growth driver for the company, but it needs to get to market first. Next month the US FDA is set to rule on approval in the project's first indication, atopic dermatitis, and the decision will be made amid close scrutiny of the safety of the Jak inhibitor class. 

The agency will also take on accelerated approvals in a panel meeting that will discuss whether six anti-PD-(L)1s, from Roche, Merck & Co and Bristol Myers Squibb, should remain conditionally available. Elsewhere, Takeda hopes to get the green light in a rare inflammatory disease where the competition is not far behind.

Jak worries remain

Toxicity is not a new concern for Jak inhibitors, but signs have emerged recently that the FDA is taking a close look at the class's safety record. The review of Abbvie’s Rinvoq in psoriatic arthritis was recently extended with the regulator requesting long-term data in this condition and atopic dermatitis, in which Rinvoq is also filed.

A similar delay cannot be ruled out for Pfizer’s abrocitinib, a follow-on project to Xeljanz. The latter has a poor safety record and a black-box warning for thrombosis and malignancies.

Abrocitinib data have not raised issues with thrombosis, major cardiac events or malignancies. However, studies in atopic dermatitis have shown a 10-20% rate of nausea and headache, as well as signs of an increased risk of thrombocytopenia and lipid disorders.

Should any of the Jaks get the go-ahead in atopic dermatitis, they will likely be used second line. Sanofi/Regeneron’s Dupixent has set a high safety and efficacy bar, and is forecast to remain the market leader until at least 2026, according to Evaluate Pharma.

Lilly is also trying to extend Olumiant’s use into atopic dermatitis, with a Pdufa date some time in the second quarter. All the Jak players will pay close attention to the progress, or otherwise, of these projects in the coming months. 

Tough stance

Another issue on which the FDA seems to be taking a harder line is accelerated approvals of anti-PD-(L)1 drugs for indications in which confirmatory studies have failed. An advisory committee meeting will take place over three days towards the end of next month to discuss six indications relating to Keytruda, Tecentriq and Opdivo.

Earlier this month, Roche pulled Tecentriq in urothelial bladder cancer, the fourth such withdrawal for an an anti-PD-(L)1 drug; this followed similar exits for Bristol Myers Squibb’s Opdivo and Merck & Co’s Keytruda, both in small-cell lung cancer, and Astrazeneca’s Imfinzi in bladder cancer (The US FDA gets tough, March 8, 2021).

The number of US approvals via the accelerated pathway has soared in recent years, and many of these remain unconfirmed.


Meanwhile, Takeda boasts that TAK-721 will become the first US-approved treatment for eosinophilic oesophagitis should it gets the thumbs up next month. The project, which will be branded Eohilia if it gets the green light, is an oral suspension of budesonide, a generic corticosteroid.

Topical steroids or proton pump inhibitors are widely used off-label in eosinophilic oesophagitis, a rare chronic inflammatory disease localised in the oesophagus.

Modest numbers are attached to TAK-721 – 2026 sales sit at $357m, according to Evaluate Pharma's sellside consensus.

And the competition is not far behind. Sanofi and Regeneron plan to file Dupixent in eosinophilic oesophagitis next year, while Astrazeneca’s Fasenra is in phase 3Phase 2/3 data with Allakos’s Siglec-8 monoclonal antibody lirentelimab are due in the fourth quarter.

The tables below list first-time and supplementary US approvals and advisory meetings due next month, with consensus forecasts from Evaluate Pharma.

Notable first-time US approval decisions due in April
Project Company Pdufa date 2026e sales by indication ($m) Note
Tanezumab Pfizer/Lilly Possibly Apr 179 Negative adcom in March
Pfizer Apr 1,127 See text
Takeda Est Apr 355 See text
SPN-812 Supernus Early Apr
265 Previous CRL, filed in paediatric ADHD
IV Tramadol Avenue Apr 12
273 Previous CRL owing to safety issues, IV version of opioid
Epsolay Sol-Gel Apr 26 - Topical cream for rosacea
Pegunigalsidase alfa Protalix Apr 27 - Adults with Fabry disease
Tralokinumab Leo Pharma Q2 - Anti-IL-13 for moderate to severe atopic dermatitis
Estelle Mithra/Mayne Pharma Group H1 - Contraceptive
Source: Evaluate Pharma & company releases.
Advisory committee meetings in April
Project Company Adcom date 2026e sales by indication ($m) Note
Donislecel Celltrans Apr 15 - Allogeneic islets of Langerhans for transplant, for treating type 1 diabetes
Tecentriq, Keytruda,
Roche, Merck & Co, Bristol Myers Squibb Apr 27-29 - Six indications given accelerated approval where confirmatory studies have failed
Sources: FDA ad com calendar & Evaluate Pharma.
Supplementary and other notable approval decisions in April
Product Company Indication (clinical trial) Date
SC Tysabri Biogen Relapsing-remitting MS (Deliver, Refine) Est Apr
Tyvaso United Therapeutics Pulmonary hypertension associated with interstitial lung disease (Increase) Apr
Nuplazid Acadia Dementia-related psychosis (Harmony) Apr 3 (Deficiencies identified in Mar)
Praluent Sanofi/
Homozygous familial hypercholersterolaemia (Odyssey HoFH) Apr 4
Ibsrela (tenapanor) Ardelyx Control of serum phosphorus in patients with chronic kidney disease on dialysis (Amplify, Phreedom, Block) Apr 29
Xeljanz Pfizer Anklyosing spondylitis (A3921120) Q2
Olumiant  Lilly Atopic dermatitis (Breeze-AD) Q2
Nurtec ODT Biohaven Prevention of migraine (Study 305, 201) Q2
Farxiga Astrazeneca CKD with or without type 2 diabetes (Dapa-CKD) Q2
Alecensa Roche First-line Alk-positive NSCLC (Bfast) Q2
Source: Evaluate Pharma & company releases.

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