The US FDA has its work cut out as the holiday season kicks off this year, with approval decisions due for two cancer-fighting kinase inhibitors in the week after America celebrates Thanksgiving.
The field of pain medicine has two big decisions pending: Acelrx Pharmaceuticals and Trevena await verdicts on their “smarter opioids”, though in the case of the latter the outlook is not good after a negative advisory committee vote on oliceridine (Olinvo). Meanwhile Merck & Co has a chance to continue its march across the oncology landscape as Keytruda looks to join Bristol-Myers Squibb’s Opdivo in liver cancer.
There could not be two more different outlooks than those for Acelrx and Trevena. Acelrx’s Dsuvia earned a 10-3 recommendation from an FDA advisory committee, a day after the same committee rejected Trevena’s oliceridine in an 8-7 vote. Since the FDA rarely overrules negative adcom votes it looks like Trevena will need to go back to the drawing board.
Dsuvia is not guaranteed approval, but its chances are better: this is the second time around with the regulator, so Acelrx’s submission should be stronger than its first try.
|Notable November first-time approval decisions|
|Product||Company||PDUFA date||Product NPV ($m)|
|Dsuvia||Acelrx Pharmaceuticals||Nov 2||157|
|Yupelri||Mylan/Theravance Biopharma||Nov 13||555|
|Aemcolo||Cosmo Pharmaceuticals||Nov 16||316|
|Emapalumab||Swedish Orpham Biovitrum||Nov 20||n/a|
|Larotrectinib||Loxo Oncology||Nov 26||927|
|Firdapse||Catalyst Pharmaceuticals||Nov 28||185|
|Gilteritinib||Astellas Pharma||Nov 29||1,548|
|Lorlatinib||Pfizer||Nov (Pfizer estimate)||1,076|
A total of three new targeted kinase inhibitors are due decisions on their first approvals in November. The crunch date for Pfizer’s lorlatinib in non-small cell lung cancer was delayed from August. The project is designed to treat patients with Alk mutations who have progressed following treatment with an Alk inhibitor like Xalkori.
Larotrectinib, meanwhile, has been submitted as a tumour-agnostic agent in patients whose disease is driven by NTRK gene fusion. And gilteritinib is due a decision in relapsed/refractory acute myeloid leukaemia in patients with a FLT3 mutation; Novartis’s Rydapt is approved first line in this indication.
As targeted agents, none of these are expected to crack $1bn in annual sales by 2024. Larotrectinib will be the closest, at $776m, according to EvaluatePharma – its applicability across multiple cancers will undoubtedly help sales.
In the rare disease category is emapalumab, a therapy for primary haemophagocytic lymphohistiocytosis. Developed by Novimmune, the anti-interferon gamma antibody was recently acquired by Swedish Orphan Biovitrum for SFr50m ($50m), with another SFr400m in milestones possible.
Firdapse could see its first US approval in the rare disease Lambert-Eaton myasthenic syndrome. Assuming that it is approved by its PDUFA date of November 28, its price will be closely watched as it is a proprietary form of 3,4-diaminopyridine, which Jacobus Pharmaceuticals has been giving patients for free. Jacobus is enrolling into a clinical trial in the hopes of matching Catalyst Pharmaceuticals.
Coherus Biosciences’ Udenyca got a complete response letter earlier this year and is now undergoing a second review. If it wins approval it will trail Mylan’s Fulphilia to market as a biosimilar competitor to Amgen’s Neulasta.
Merck & Co’s Keytruda, meanwhile, looks to take on its rival Opdivo in another indication in which the Bristol-Myers Squibb cancer drug arrived first. The setting is hepatocellular carcinoma patients who have progressed following treatment with Sutent.
The only question here is whether the FDA will grant an accelerated approval based on the basis of the Keynote-224 trial, an uncontrolled, open-label phase II study, or delay a decision until the pivotal, front-line Keynote-224 and 394 trials report. The recent stance of the FDA when it comes to immuno-oncology would make betting on the former the smart wager.
|Supplementary approvals and other notable regulatory decisions for November|
|Udenyca||Coherus Biosciences||Neulasta biosimilar||Nov 3|
|Keytruda||Merck & Co||sNDA/BLA for Keytruda for 2nd-line hepatocellular carcinoma||Nov 9|
|Promacta||Novartis/Ligand||sNDA/BLA for Promacta for severe aplastic anemia||Nov (Evaluate estimate)|
|Basalog||Mylan||Lantus biosimilar filed in Nov 2017, approval date unclear.||Nov (Evaluate estimate)|
|Vesicare||Astellas Pharma||sNDA/BLA for Vesicare for neurogenic detrusor overactivity in paediatric patients||Nov (Evaluate estimate)|