Go or no go? Big decisions loom for Bristol and Sanofi

The FDA will have a busy November, with decisions due for Bristol, Sanofi and Y-mabs, among others.

The most eagerly awaited regulatory event of November is the advisory committee meeting for Biogen's Alzheimer's candidate aducanumab, but there are plenty of other projects awaiting US FDA approval decisions too.

The biggest is Bristol Myers Squibb’s Car-T candidate lisocabtagene maraleucel, and the verdict is one component that will determine whether holders of a contingent value right receive a payout. Meanwhile, Sanofi and Y-mabs are set to hear about rare disease assets.

The FDA is due to decide on liso-cel by November 16, and approval for diffuse large B-cell lymphoma must occur by December 31 for the contingent value right agreed as part of Bristol's takeover of Celgene to pay out. 

Data presented from the Transcend-NHL trial at Ash last year were hardly a home run, with liso-cel looking no better than Gilead’s rival Car-T Yescarta across a variety of metrics including remission rates and survival. Also, on the manufacturing side, the success rate with liso-cel was worryingly low.

In liso-cel’s corner is safety, as its profile appears meaningfully better than that of Yescarta and Novartis’s Kymriah. But the big question is whether, with two similar treatments already on the market, data from an uncontrolled, single-arm study are enough to convince the FDA.

Another component that must be met for the contingent value right to pay is ide-cel, and this has a Pdufa date of March 27, just four days before its own deadline.

Rare diseases

While Sanofi’s $11.6bn acquisition of Bioverativ in 2018 was focused on haemophilia therapies, it also brought sutimlimab, which has a Pdufa date of November 13. The project is filed in cold agglutinin disease (CAD), a complement-mediated and very rare form of autoimmune haemolytic anaemia.

Sutimlimab is an anti-C1s MAb targeting the complement pathway – a novel approach. Current first-line therapy is B cell-directed and includes rituximab, which is said to be effective in about 60% of cases. In cases of severe anaemia blood transfusions are given as a temporary measure.

Sutimlimab’s filing was based on the-single arm Cardinal study in patients who had received transfusions. 54.2% responded, meeting the primary endpoint, while 71% remained free of transfusions to week 26.

Elsewhere, Y-mabs’ lead project, naxitamab, is due a decision towards the end of next month after gaining priority review. The anti-GD2 MAb, trademarked Danyelza, is filed for use in children with relapsed/refractory high-risk neuroblastoma.

This submission was based on two phase II studies, 201 and 12-230, with the latter showing a 78% ORR in primary refractory patients and 37% ORR in secondary refractory patients resistant to salvage therapy. In study 201 there was a 79% ORR and 71% complete response rate.

Y-mabs is keen to point out the advantages over United Therapeutics’ Unituxin, another anti-GD2 MAb. Unituxin, used as a front-line treatment, is given via a 10 to 20-hour infusion, four times per week, while Danyelza is a more convenient 30-minute infusion three times a week. Danyelza also eliminates the need for the patient to have had prior autologous stem cell transplant.

Danyelza’s own front-line study is ongoing and has a primary completion date in 2022.

The tables below list first-time and supplementary US approvals, as well as panel meetings due in November, with consensus forecasts from EvaluatePharma.

Advisory committee meetings in November
Project Company Adcom date Sales by indication ($m) Note/Vantage link
Olas Pharma Nov 2 - Resubmitted, post-op pain 
Aducanumab Biogen/Eisai Nov 6 4,632

Alzheimer's treatment, Pdufa set for Mar 7, 2021 (Aducanumab’s day of reckoning approaches)

Source: FDA adcom calendar & EvaluatePharma.


Notable first-time US approval decisions due in November
Project Company PDUFA date  Sales by indication  ($m) Note/Vantage link
SPN-812 Supernus Nov 8 279 Project has not been shown to be any better than Lilly’s non-stimulant ADHD drug Strattera, which lost patent protection in 2017 (Supernus struggles to gain attention)
Sutimlimab Sanofi Nov 13 546 See text
AR19 Arbor Nov 15 - ADHD treatment, adcom voted 19-2 that safety risks outweighed the benefit of the immediate-release, amphetamine sulfate capsule 
ALKS 3831  Alkermes Nov 15 362 Positive adcom in October (Could Alkermes’ new antipsychotic punch below its weight?)
Zimhi Adamis Nov 15 (resubmission) 160 CRL in November 2019 relating to CMC
Liso-cel/JCAR017/Breyanzi  Bristol Myers Squibb Nov 16 1,154 See text
Zokinvy (Ionafarnib) Eiger Nov 20 99 Treatment of progeria and progeroid laminopathies (in Ph3 for Hep D)
LIQ861 Liquida Technologies Nov 24 476 Inhaled dry powder formulation of treprostinil
Revance Nov 25 366 Long-acting neurotoxin filed to treat frown lines (Revance irons out the wrinkles with its longer-acting Botox)
Setmelanotide Rhythm Nov 27 799 Filed in two rare genetic obesity indications, pro-opiomelanocortin deficiency obesity and leptin receptor deficiency obesity
Danyelza (naxitamab) Y-mabs Nov 30 390 See text
Dostarlimab GSK Q4 542 Anti-PD-1 filed in endometrial cancer
Sources: EvaluatePharma & company releases.


Supplementary and other notable approval decisions in November
Product Company Indication (clinical trial) Date Vantage link
Xofluza Roche Three decisions: 1) new formulation as one-dose granules for oral suspension,  2) for the treatment of acute uncomplicated influenza in children aged 1-12, 3) post-exposure prophylaxis of influenza in people aged 1 and over (miniStone-2 and Blockstone) Nov 23 -
Keytruda + chemo Merck & Co Triple negative breast cancer (≥10% PD-L1 expressers) (Keynote-355 Nov 28 Keytruda challenges Tecentriq on its home turf
Brilinta Astrazeneca/ Merck & Co Acute ischaemic stroke or transient ischaemic attack (Thales) Q4 Go or no go? Vaccine panel upstages US approval decisions, The cost to Astrazeneca of building Brilinta
Imfinzi Astrazeneca Four-week fixed-dose regimen for NSCLC and bladder cancer (several trials, incl Caspian) Q4 -
Alecensa Roche 1L NSCLC, using FoundationOne Liquid to detect patients with Alk fusions (Cohort A, B-Fast study)  Q4 Esmo 2019 – Foundation eyes liquid biopsy rule change
Sources: EvaluatePharma & company releases.

Share This Article