Go or no go? Bristol's first-in-class hopes
April should mark the approval of some of the biggest drugs of 2022, including Alnylam's vutrisiran, while TG will hope to be spared pain at the PI3K adcom.
Bristol Myers Squibb will hope to have the first-in-class treatment for hypertrophic cardiomyopathy by the end of the month, if mavacamten can overcome safety concerns.
Three Chinese companies are also set to test what the FDA finds acceptable when it comes to patient diversity in trials, while TG Therapeutics' Ukoniq faces an advisory panel decision on the efficacy of its combination drug U2 in chronic lymphocytic leukaemia.
First in class
With Revlimid generics expected later this year Bristol Myers Squibb is counting on the approval and then success of mavacamten, its cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy (HCM). If mavacamten is a hit it will help justify the $13.1bn Bristol spent to acquire Myokardia in 2020.
HCM is a genetic disease that causes the thickening of heart muscles, obstructing blood flow. With no approved therapies a quick FDA green light might seem a given, but the approval decision has already been delayed by three months after the agency asked for more time to review the safety data.
Even if mava is approved the FDA is widely expected to request post-marketing data on morbidity and mortality. But Berenberg analysts are not expecting this to blunt take-up: they forecast peak revenues of $4bn in obstructive HCM, which should go some way to helping fill the gap of declining Revlimid sales.
Convenience not everything
Another one of the biggest expected approvals of the year is Alnylam’s vutrisiran in polyneuropathy of hereditary ATTR amyloidosis. The RNAi therapy is the company’s more convenient follow-on to Onpattro, which was approved in 2018.
Despite its every-three-weeks subcutaneous delivery, compared with Onpattro’s similarly spaced infusions, some analysts suggest that use could be confined to newly diagnosed patients given the 90% compliance rate for Onpattro. Even so, vutisiran's consensus forecasts for 2026 sales are, at $1.8bn, double those of Onpattro for that year.
Same, same, not different
Three of April’s FDA approval decisions involve China-based companies, but the regulator might have a surprise in store for at least two of these. Coherus/Shanghai Junshi and Akeso/Sino’s respective toripalimb and penpulimab are up for approval in third-line nasopharyngeal carcinoma, but supporting data come only from China.
This was one of the facts that tripped up Lilly/Innovent’s sintilimab in February after an advisory committee voted 14-1 against approval, citing the difficulty in generalising the study findings to the US population.
Given relatively niche indication of nasopharyngeal carcinoma toripalimb and penpulimab could still get approved. If they do, it will give a further steer on how the FDA might treat the other anti-PD-(L)1s with China-only data.
Thanks to a US bridging study supplementing two Chinese trials Huchmed should avoid some of the uncertainty around homogenous patient groups when surufatinib comes before the FDA.
Surufatinib, a treatment for pancreatic and extra-pancreatic neuroendocrine tumours (NETs), has also showed impressive effectiveness, with two pivotal Chinese studies finishing early due to efficacy. The company's claim that surufatinib can treat NETs produced from any organ, if true, could give Pfizer’s Sutent and Novartis’s Afinitor some competition as these are effective in only 70% of NET patients.
A greenlight would mark Hutchmed’s first approval outside China. The only sticking point might be the FDA's ability to complete manufacturing inspections, a hurdle that has tripped the likes of UCB and Sol-Gel, which are now respectively looking for approval for Bimzelx and Epsolay.
Pain at the panel?
The FDA’s advisory committees will be kept busy this month, with the first order of business being a look at Covid preparedness. While the adcom will not discuss specific vaccine applications, or cast votes, a recommendation for widespread fourth booster shots or vaccines for the Omicron variants will be a bonus for Moderna and Pfizer.
In contrast a review of the PI3K-delta class, which has read-across for an April adcom of TG Therapeutics' U2 and Ukoniq, is unlikely to generate good news for those concerned. The FDA will be looking at Ukoniq's approved lymphoma settings, but also its worrying lack of survival benefit when combined with ublituximab in chronic lymphocytic leukaemia.
As for the wider PI3K-delta inhibitor class, many have been given accelerated approval based on single-arm studies. The agency will now decide if randomised data should be the standard for approval, and has already rejected MEI’s zandelisib.
The tables below lists 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 April|
|Project||Company||Pdufa date||Indication(s)||2026e sales by indication (SBI) ($m)||Note|
|Tuoyi (toripalimab)||Coherus/ Shanghai Junshi||April||Nasopharyngeal carcinoma (NPC)||-||Anti-PD-1 MAb, Tuoyi + chemo for 1L NPC and monotherapy for 2L+ NPC|
|BXCL501||Bioxcel||April 5||Agitation associated with schizophrenia and bipolar disorders I and II||378||Delayed from Jan. FDA requested analyses of clinical data|
|Vutrisiran||Alnylam||April 14||Polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis||1,828*||Subcutaneous follow-on to Onpattro, filing based on Helios-A|
|Mavacamten||Bristol Myers Squibb||April 28||Obstructive hypertrophic cardiomyopathy||1,672||Delayed from Jan owing to updates to the proposed REMS|
|AXS-07||Axsome||April 30||Acute treatment of migraine||128||Combination of rizatriptan and the Cox-2 NSAID meloxicam|
|Hutchmed||April 30||Pancreatic and non-pancreatic neuroendocrine tumours||362||If approved would be Hutchmed's first marketed oncology drug outside China|
|Akeso/Sino||Est H1||3L nasopharyngeal carcinoma||-||See text|
|Bimzelx||UCB||H1||Plaque psoriasis||952||Decision delayed in Oct owing to Covid travel restrictions|
|Epsolay||Sol-Gel||Pending||Papulopustular rosacea||-||Pre-approval inspection had been scheduled for mid-Feb|
|FT218||Avadel||Pending||Narcolepsy||321||Delayed in Oct|
|SH-111||Shorla Oncology (private)||Pending||T-cell leukaemia||-||FDA filing accepted Apr 2021|
|*SBI as amyloidosis. Source: company statements & Evaluate Pharma.|
|Advisory committee meetings in April|
|Project||Company||Adcom date||Indication||2026e sales by indication (SBI) ($m)||Note|
|Covid-19 vaccination||No product-specific applications will be discussed||April 6||Covid-19 prevention||-||Will discuss use of Covid vaccine booster doses and the process for vaccine strain selection to address current and emerging variants|
|PI3K inhibitor class||N/A*||April 21||Haematologic malignancies||-||Will discuss whether randomised data should be required (MEI suffers from the FDA’s brake on accelerated approvals)|
|U2, Ukoniq||TG Therapeutics||April 22||Haematologic malignancies||1,188||Will discuss U2 for CLL or SLL, and existing Ukoniq accelerated pathway for r/r FL & MZL|
|*No details have been provided on whether specific products will be discussed. Source: FDA adcom calendar & Evaluate Pharma.|
|Supplementary and other notable approval decisions due in April|
|Product||Company||Indication (clinical trial)||Date|
|Vaxneuvance||Merck||Prevention of invasive pneumococcal disease in children 6 weeks to 17 years old (15-valent conjugate vaccine, PNEU-PED)||Apr 1|
|Yescarta||Gilead||2L large B-cell lymphoma (Zuma-7)||Apr 1|
|Regeneron||Treat Covid in non-hospitalised patients and as prophylaxis||Apr 13 (already has EUA)|
|Qelbree||Supernus||ADHD in adults (P306)||Apr 29|
|Ultomiris||Astrazeneca||Generalised myasthenia gravis (NCT03920293)||Q2|
|Enhertu||Astra/Daiichi||Her2+ve breast cancer after anti-Her2-therapy (Destiny-Breast 03)||Q2|
|Olumiant||Lilly||Treatment of certain hospitalized patients with Covid||Q2 (already has EUA)|
|Olumiant||Lilly||Atopic dermatitis (Breeze-AD)||Pending|
|Kymriah||Novartis||3L FL (ph2 Elara)||Pending|
|Source: company statements & Evaluate Pharma.|
Updated: Bayer's Aliqopa decision (Chronos-3) removed as the filing was withdrawn in December 2021.