Go or no go? A busy month ahead for US FDA decisions

June will be hectic for the US regulator, with many approval decisions due, including one for subcutaneous Arzerra in multiple sclerosis and Tazverik in follicular lymphoma.

Upcoming Events

No fewer than 13 first-time and nine supplemental approval decisions are pending for the US FDA in June. At the halfway point last year 18 first-to-market products had been approved, and 2020 numbers look a little healthier, even with the Covid-19 pandemic − the tally so far is 23 first-time approvals, with June still to come.

Some of the more interesting outcomes are expected in the supplemental decisions, including the use of Novartis’s subcutaneous formulation of ofatumumab, Arzerra's active ingredient, in multiple sclerosis. The pivotal studies, Asclepios I and II, showed reductions in annualised relapse rate of 51% and 59% versus Sanofi’s Aubagio in relapsing MS.

Aubagio is a low bar to beat. Roche’s blockbuster Ocrevus, an anti-CD20 MAb like Arzerra, has been on the market for relapsing and progressive forms of MS since 2017, and at $3.5bn is forecast to be the biggest seller in relapsing MS by 2026.

Novartis’s project takes third place with 2026 sales of $2.6bn, according to EvaluatePharma sellside consensus. This could be a reprieve for the MAb, the intravenous version of which has disappointed in CLL.

Also due is a decision is Epizyme’s oral EZH2 inhibitor Tazverik in follicular lymphoma – a much bigger opportunity than the indication for which the drug is approved, epithelioid sarcoma. In a phase II study in at least third-line subjects the objective response rate was 69% for patients with an EZH2 mutation and 35% for those with wild-type EZH2. The filing was accepted without the need for a companion diagnostic, but analysts think some clinicians may opt to test for EZH2 before treatment.

Leerink notes that Tazverik has a much better tolerability profile and more convenient administration than other drug classes such as P13K inhibitors. To support full approval an adaptive trial is being run combining Tazverik with Revlimid plus Rituxan.

The pending judgement on Keytruda in advanced cutaneous squamous cell carcinoma (CSCC) will be based on data from the Keynote-629 study, which showed an objective response rate of 34%.  CSCC is an aggressive tumour, and Regeneron/Sanofi’s Libtayo is the only PD-1 antibody currently approved, on the basis of a 47% ORR.

Supplementary and other notable approval decisions in June
Product Company Indication (clinical trial) Date
Subcutaneous ofatumumab/OMB 157 Novartis Relapsing MS (Asclepios I and II) Jun
Basalog (Lantus biosimilar) Biocon Diabetes types 1 & 2 (previous CRL) Jun
Cyramza Lilly 1L EGFR-positive NSCLC (Relay) Est H1 2020
Recarbrio Merck & Co Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by certain susceptible Gram -ve microorganisms (Restore-Imi 2) Jun 4
Keytruda Merck & Co ≥2L TMB-high (≥10 mut/mB) tumours (Keynote-158) Jun 16
Crysvita/borosumab Ultragenyx FGF23-related hypophosphatemia associated with phosphaturic mesenchymal tumors (NCT02304367, NCT02722798) Jun 18
Tazverik/tazemetostat Epizyme ≥3L r/r follicular lymphoma (NCT01897571) Jun 18
Xpovio/selinexor  Karyopharm ≥3L r/r DLBCL (Sadal) Jun 23
Keytruda Merck Recurrent and/or metastatic CSCC not curable by surgery or radiation (Keynote-629) Jun 29
Sources: EvaluatePharma & company releases.

First-timers

Intercept’s Nash project obeticholic acid, available as Ocaliva for primary biliary cholangitis, had a panel and a PDUFA date set for June, but the adcom was postponed after an additional data request by the FDA, and the approval decision date will likely be missed. This is a second slip for the panel, which had initially been scheduled for April but was delayed by the Covid-19 pandemic.

The Astrazeneca spinout Viela Bio could have its first approved product next month. The anti-CD19 MAb inebilizumab is filed in neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune condition that often leads to irreversible blindness and paralysis.

The filing is based on the pivotal N-Momentum trial where inebilizumab reduced the risk of developing an NMOSD attack by 77% versus placebo in aquaporin 4-positive patients after 28 weeks of treatment. Aquaporin 4-antibodies are a key biomarker for disease.

Viela Bio has close competition for a US market that comprises around 4,000-8,000 patients. Alexion’s Soliris gained approval in aquaporin 4-positive NMOSD last June, and its follow-on ultomiris is in phase III. Roche’s satralizumab was filed last August and a decision on that project is expected this year, though no date has been given.

Another eye drug, Abbvie’s Abicipar, is under review in wet age-related macular degeneration. It came with Abbvie’s acquisition of Allergan.

Two phase III trials, Cedar and Sequoia, met their primary endpoints, showing non-inferiority over Roche’s older AMD therapy Lucentis on vision stability. But there were questions over how vision loss was evaluated, as well as a higher incidence of intraocular inflammation with abicipar. A third study, Maple, used a new formulation, but rates of inflammation were still well above those with Regeneron’s Eylea.

Eylea is the dominant drug in wet AMD, and competition will only become fiercer when biosimilar versions of Lucentis and Eylea hit the market, expected in 2021 and 2024 respectively.

The table below lists the rest of the first-time approvals due in June, and consensus forecasts from EvaluatePharma.

Notable first-time US approval decisions due in June
Project Company PDUFA date 2026e sales ($m) Note
Posimir Durect H1 2020 (resubmission) 294 Adcom voted six for and six against approval
Abicipar  Abbvie Mid year 206 See above
Aximris XR (oxycodone) Intellipharmaceutics Q2 (resubmission) 43 Negative adcom, 24-2 against approval
Travivo Fabre-Kramer Q2 - -
FMX103 Menlo Therapeutics Jun 2 112 Foam formulation of the antibiotic minocycline
Inebilizumab Viela Bio Jun 11 586 (neuromyelitis optica) See above
Contepo (fosfomycin) Nabriva Jun 19 (resubmission) 117 IV fosfomycin has been generic in Europe for many years, but has never been approved in the US
Gimoti Evoke Jun 19 (resubmission) 72 Developed to treat diabetic gastroparesis in women; FDA has raised concerns about chemistry, a lack of adequate clinical data to support sex-based efficacy differences, and clinical pharmacology
Fintepla Zogenix Jun 25 369 (Dravet) Decision extended from March on additional data submitted by Zogenix; Fintepla has a clinical edge over GW Pharma’s Epidiolex, but the latter has been on the market since 2018
HTX-011 Heron Jun 26 (resubmission) 604 Non-opioid painkiller aimed at the post-op market; decision extended from Mar; previous CRL over manufacturing problems
Mycapssa Chiasma Jun 26 (resubmission) - First oral somatostatin analogue for maintenance treatment of acromegaly, potentially replacing similarly acting injected drugs; earlier application based on single-arm trial was rejected in 2016
Ocaliva (obeticholic acid) Intercept Jun 26 3,017 June adcom postponed so PDUFA date will likely be extended
Sources: EvaluatePharma & company releases.

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