September is shaping up to be a big month for Calliditas. The Swedish group’s Nefecon, a gut-targeted formulation of the steroid budesonide, might become the first approved therapy for IgA nephropathy, a rare kidney disorder.
Other projects with FDA decisions pending include an oral migraine project from Abbvie, while Mirum is hoping for a rare disease win with maralixibat. Two of the most notable verdicts due in September came early, however: for Ascendis's growth hormone lonapegsomatropin and Bristol Myers Squibb’s Opdivo, which became the first adjuvant immunotherapy for patients with high-risk urothelial cancer in the US.
The checkpoint inhibitor won approval off the back of Checkmate-274, in which Opdivo after surgery nearly doubled median disease-free survival to 21.0 months, versus 10.9 months for placebo recipients, amounting to a 30% reduction in disease recurrence at any point in the trial (p=0.0006) (Asco-GU – Bristol in pole position with Opdivo’s adjuvant use, February 9, 2021).
Meanwhile, approval of Ascendis's lonapegsomatropin, now branded Skytrofa, marks the first FDA green light for the group. Skytrofa is expected to be one of the biggest drug approvals in 2021, with 2026 sales forecast to reach $1.5bn in paediatric patients with growth hormone deficiency.
The company might have little time before competition arrives in the shape of Pfizer/Opko’s somatrogon, also once weekly, which has a Pdufa in October. However, somatrogon has so far only shown non-inferiority to daily injections (Pfizer’s growth hormone falls short, October 22, 2019). Novo Nordisk’s once-weekly candidate somapacitan is further behind, with data from a paediatric phase 3 study expected in the fourth quarter.
Meanwhile, Calliditas’s Nefecon is still awaiting its decision. Systemic steroids are often used off-label in IgA nephropathy, but come with side effects such as high blood pressure, weight gain and infection.
Nefecon was filed for accelerated approval based on part A of the phase 3 Nefigard study, which showed statistically significant proteinuria reduction compared with placebo, as well as stabilisation of estimated glomerular filtration rate (eGFR) at nine months. The project was said to be generally well-tolerated.
Part B of the same study, measuring eGFR at two years, will provide confirmatory data for approval. Data are expected in early 2023. Calliditas is planning a solo launch in the US, which will be a big test for the Swedish biotech. In Europe the company has signed up Stada as partner in a deal worth €20m ($24m) up front. A European approval decision is expected in the first quarter of next year.
Gene therapy scrutiny
Lastly, a two day panel in early September is set to discuss the safety of adeno-associated virus (AAV) vector gene therapies, a space that has been rocked by adverse event scares.
The meeting will discuss the oncogenicity, hepatotoxicity, thrombotic microangiopathy and non-clinical as well as clinical findings of neurotoxicity.
Although no companies have been specifically mentioned the panel is potentially relevant for companies with AAV projects such as Regenxbio, Applied Genetic Technologies, Gensight, Biomarin, Uniqure and Novartis. The latter’s intrathecal formulation of Zolgensma had its partial clinical hold lifted recently, nearly two years after a preclinical safety issue.
|Notable first-time US approval decisions due in September|
|Project||Company||PDUFA date||Indication(s)||2026e sales by indication ($m)||Note|
|Trudhesa (INP104)||Impel Neuropharma||Sept 6||Acute migraine treatment||-||Delivered directly to upper nasal space|
|Nefecon||Calliditas||Sept 15||IgA nephropathy||798*||See text|
|VP-102||Verrica||Sept 23 (resubmitted)||Molluscum contagiosum||271||CRL in July 2020 due to CMC issues, Pdufa extended from June|
|Maralixibat||Mirum||Sept 29||Cholestatic pruritus in Alagille syndrome||598**||Maralixibat inhibits the apical sodium dependent bile acid transporter; Alagille syndrome is a rare genetic disorder in which bile ducts are abnormally narrow|
|Reltecimod||Atox Bio||Sept 30||Resolution of organ dysfunction in necrotising soft tissue infections||-||Filed under accelerated approval|
|Atogepant||Abbvie||Late Q3||Episodic migraine prevention||948||Oral CGRP antagonist. Biohaven's Nurtec ODT, also oral, is already on the market for preventation|
|Epsolay||Sol-Gel||Estimated Q3||Papulopustular rosacea||-||Delayed in April, no new date disclosed|
|Takeda||Q3/Q4||Eosinophilic oesophagitis||337||No specific date disclosed, filing with priority review accepted by FDA in Dec 2020|
|*Includes undisclosed partner sales, **SBI for general liver disorders. Source: Evaluate Pharma & company releases.|
|Advisory committee meeting in September|
|Sept 2-3||Cellular, tissue, and gene therapies panel to discuss the toxicity risks of AAV vector-based gene therapy products.|
|Source: FDA ad com calendar.|
|Supplementary and other notable approval decisions in September|
|Product||Company||Indication (clinical trial)||Date|
|Repatha||Amgen||Paediatric patients with heterozygous familial hypercholesterolemia||Estimated Sept|
|Alvotech/Teva||PK study AVT02-GL-101, efficacy study AVT02-GL-301||Sept|
|Paliperidone palmitate 6-month (PP6M)||J&J||Adults with schizophrenia (Route 6)||Estimated Sept 2|
|Impel||505(b)(2) application acute treatment of migraine (dihydroergotamine mesylate with olfactory delivery)||Sept 6|
|Brukinsa||Beigene||Marginal zone lymphoma who have received at least one prior anti-CD20-based therapy (Magnolia, Ph1/2)||Sept 19|
|Ruxolitinib cream||Incyte||Atopic dermatitis (TruE-AD1, TruE-AD2)||Sept 21
(extended from June)
|Jakafi||Incyte/Novartis||Paediatric patients with steroid-refractory GVHD (Reach3)||Sept 22
(extended from June)
|Source: Evaluate Pharma & company releases.|