Go or no go? Bristol’s Tyk2 test

A green light from the FDA is expected for deucravacitinib, while Amylyx, Ferring and Oncopeptides head for panels.

September will see an approval decision on one of the year’s biggest expected launches, Bristol Myers Squibb’s deucravacitinib. A green light is expected for the oral Tyk2 inhibitor in psoriasis, but whether the project can escape a Jak-like label is less certain. 

Meanwhile, several panels are due, including a second for Amylyx’s ALS contender AMX0035. The company comes armed with further data cuts, a strategy also being taken by Oncopeptides, which withdrew its multiple myeloma project Pepaxto last year, before changing its mind. Separately, Ferring’s RBX2660 will be the first microbiome project to come in front of a US panel.  

Green light 

Bristol's oral Tyk2 inhibitor deucravacitinib impressed in two phase 3 studies in psoriasis, beating Amgen’s Otezla, also oral, in the Poetyk PSO-1 and 2 trials.  

While approval is expected, and safety looked clean, investors want to know whether the FDA assigns a black-box warning referencing Jak-class toxicity risks, as Tyk2 is part of the Jak family. 

Psoriasis is an incredibly crowded space, and, while it looks like deucravacitinib can take some of Otezla’s market, on efficacy Bristol's project falls short of biologics such as Abbvie’s Skyrizi on a cross-trial basis. Skyrizi is expected to lead the psoriasis market by 2028, with forecast sales of $6.5bn that year, while deucravacitinib's forecasts sit at $1.6bn. 

Second time’s a charm 

Amylyx’s ALS candidate AMX0035 is heading for its second panel next month, a rare regulatory occurrence perhaps spurred by the FDA's determination to avoid a repeat of the Aduhelm debacle. AMX0035's Pdufa date is set for the end of the month.  

The first adcom back in March was narrowly negative, with a vote of 6-4 that efficacy had not been established. There were questions over the statistical analyses and rigour of the phase 2 Centaur result, which showed a modest p value of 0.034 on its primary endpoint, ALSFRS-R.  

The upcoming panel will see additional analyses from Centaur, including prespecified analyses showing that early treatment with AMX0035 was linked with a lower incidence of key events such as tracheostomy and first hospitalisation.  

Also, post-hoc analyses suggest an improved survival benefit for AMX0035 after adjusting for placebo crossover. The latest analyses show an overall survival benefit ranging from 10.6 to 18.8 months, versus 6.9 months in the original prespecified intent-to-treat analysis.   

Since Amylyx’s first panel, AMX0035 was approved in Canada, where the therapy is known as Albrioza. The conditions of the approval include supplying data from the ongoing phase 3 Phoenix trial, as well as additional planned or ongoing studies. Phoenix’s primary completion date is November 2023. 

Enema, anyone? 

Several other assets also face FDA adcoms, including Ferring’s RBX2660, also known as Rebyota, designed to reduce recurrent Clostridioides difficile infection after antibiotic treatment. 

This will be the first microbiome-based project to go before the US regulators. Privately held Ferring gained Rebyota, which comprises mixed bacteria consortia, from Rebiotix in 2018. 

Ferring has touted a clinical response of 70% versus 58% with placebo, achieved by a Bayesian analysis of the phase 2 Punch CD2 and phase 3 Punch CD3 trials. Treatment also provided a relative reduction of infection recurrence of 29%, and safety was said to be comparable to placebo. 

While the first hurdle for RBX2660 is getting past the adcom, if it does make it to market its delivery route, via an enema, is likely to be a commercial disadvantage. Competitors such as Seres/Nestlé, Finch, Vedanta and Destiny Pharma all have oral microbiome projects in development.  

There are scant details on Ferring’s own oral follow-on project RBX7455, which looks to have completed a phase 1 C diff study in 2020. 

Another chance 

Oncopeptides' Pepaxto also faces a panel next month. The writing looked to have been on the wall for the multiple myeloma chemotherapy when it was withdrawn from the US market last October, after its confirmatory Ocean study, in third to fifth-line therapy, suggested that it increased the risk of death versus Pomalyst.

However, in January Oncopeptides rescinded the withdrawal after carrying out further analyses of what it called heterogenous overall survival data. 

A new cut of Ocean, released last year, showed that overall survival numerically favoured Pepaxto in patients without a prior autologous stem cell transplant, and favoured Pomalyst in patients with a prior transplant. 

Around 50% and 40% of multiple myeloma patients receive a stem cell transplant as first-line therapy in the US and EU respectively, so Pepaxto could still reach half the market if the FDA agrees and approves it with a restricted label.  

In Europe, the CHMP gave a positive opinion indicating Pepaxti, as it is known there, for patients who have had at least three prior lines of therapy; for patients with prior stem cell transplant the time to progression should be at least three years from transplantation. 

The tables below list first-time and supplementary US approval decisions, as well as advisory committee meetings, due next month, with consensus forecasts from Evaluate Pharma. 

Notable first-time US approval decisions due in September
Project Company Pdufa date Indication(s) 2028e sales by indication ($m) Note
Daxibotulinum-toxinA (Daxi) Revance Sep 8 (resubmitted) Moderate-to-severe glabellar lines 523 CRL in Oct 2021 over manufacturing reinspection
Rolontis (eflapegrastim) Spectrum Sep 9 (resubmitted) Chemotherapy-induced neutropenia 297 CRL in Aug 2021 over manufacturing reinspection
Deucravacitinib Bristol Myers Squibb Sep 10 Moderate to severe psoriasis 1,633 Tyk2, see text
Elivaldogene autotemcel 
(eli-cel, Skysona)
Bluebird Sep 16 Cerebral adrenoleukodystrophy 21 Positive adcom in June
Pedmark Fennec Sep 23 (resubmitted) Prevention of platinum-induced ototoxicity in paediatric patients 137 CRL in Dec 2021 over manufacturing deficiencies
Amylyx Sep 29 ALS - See text

Futibatinib (TAS-120)

Taiho Oncology/Otsuka Sep 30 Patients with previously treated cholangiocarcinoma with FGFR2 gene rearrangements, including gene fusions 80 FGFR 1, 2, 3 & 4 inhibitor, NDA based on pivotal ph2b Foenix-CCA2 (Incyte’s Pemazyre and Bridgebio’s Truseltiq are both in FGFR2-mutant disease)
Tecvayli (teclistamab) Johnson & Johnson Pending R/R multiple myeloma  260 Bispecific T-cell engager targeting BCMA (Go or no go? J&J’s bispecific FDA first)
Annik (penpulimab) Akeso/Sino Pending 3L nasopharyngeal carcinoma - China-backed US approvals continue to hang in the balance
Source: company releases & Evaluate Pharma.


Advisory committee meetings due in September
Project Company Adcom date Indication 2028e SBI ($m) Note
Albrioza (AMX0035) Amylyx Sep 7 ALS - See text
Rebyota (RBX2660) Ferring (private; via Rebiotix) Sep 22 Reduce recurrence of C difficile infection in adults following antibiotic treatment for recurrent infection - See text
Poziotinib  Spectrum Sep 22 Patients with previously treated, locally advanced/metastatic NSCLC with Her2 exon 20 insertion mutations 346 Filing based on ph2 Zenith20 study, failed in EGFR exon 20 insertions
Pepaxto (melphalan flufenamide) Oncopeptides Sep 22 Adults with r/r multiple myeloma who have received at least 4 prior therapies, and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent & one CD38-directed MAb 141 See text
Copiktra (duvelisib) Secura Bio/Verastem/
Sep 23 Adult patients with r/r chronic lymphocytic leukaemia or small lymphocytic lymphoma after at least two prior therapies - PI3K delta & gamma inhibitor, approved under 505(b) pathway, discuss final OS data from Duo study
Source: FDA adcom calendar, company releases & Evaluate Pharma.


Supplementary and other notable approval decisions due in September
Product Company Indication (clinical trial) Date
Orkambi Vertex Patients with cystic fibrosis aged 12mth to <24mth Sep 4
Libtayo Regeneron 1L NSCLC (+chemo; Empower-Lung 3) Sep 19 (delay expected due to travel complications around a clinical trial site inspection in Eastern Europe)
Dupixent Sanofi/
Prurigo nodularis (Prime 2Prime) Sep 30
Imfinzi + chemo  Astrazeneca 1L biliary tract cancer (Topaz-1) Q3
Actemra Roche Hospitalised Covid patients (EUA in Jun 2021; Empacta, Covacta, Remdacta, Recovery) H2
Ronapreve (Regen-Cov) Regeneron Treatment of Covid-19 in non-hospitalised patients and as prophylaxis in certain individuals; given EUA in Nov 2020, limited Jan 2022 after emergence of omicron (NCT04425629, NCT04452318) Pending
Source: company releases & Evaluate Pharma.

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