To go or not to go? Bristol’s first-class hopes

Bristol Myers Squibb will hope to have first-class treatment for hypertrophic cardiomyopathy by the end of the month if mavacamten can overcome safety concerns.

Three Chinese companies are also ready to test what the FDA considers acceptable in terms of patient diversity in the studies, while TG Therapeutics’ Ukoniq is facing an advisory panel decision on the effectiveness of its combined drug U2 in chronic lymphocytic leukemia.

First in class

Revlimid generics expected later this year Bristol Myers Squibb expects the approval and subsequent success of mavacamten, its cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy (HCM). If mavacamten is a hit, it will help justify the $ 13.1 billion Bristol spent on acquiring Myocardium in 2020.

HCM is a genetic disease that causes the heart muscle to thicken, thus preventing blood flow. Without approved therapies, the FDA’s fast green light may seem obvious, but the approval decision has already been delayed three months after the agency asked for more time to review safety data.

Although approved, the FDA is generally expected to request post-market morbidity and mortality data. However, Berenberg analysts do not expect it to dull it: they predict maximum revenues of $ 4 billion in obstructive HCM, which should help fill the gap in Revlimid’s declining sales.

Comfort is not everything

Another of the largest expected approvals this year is Alnylam vutrisiran in polyneuropathy of hereditary ATTR amyloidosis. RNAi therapy is a more convenient continuation of Onpattro, which was approved in 2018.

Despite subcutaneous administration every three weeks compared to Onpattro infusions at similar intervals, some analysts suggest that use could be limited to newly diagnosed patients due to a 90% compliance rate for Onpattro. Nevertheless, vutisiran’s consensus forecasts for sales in 2026 at $ 1.8 billion are double that of Onpattro for that year.

Same, same, not different

Three of the April FDA approval decisions concern companies based in China, but the regulator may have a surprise in store for at least two of them. The relevant toripalimb and penpulimab from Coherus / Shanghai Junshi and Akeso / Sino are ready for approval for third-line nasopharyngeal carcinoma, but supporting data are from China only.

This was one of the facts raised by Lilly / Innovent’s sintilimab in February after the advisory committee voted 14-1 against the approval, saying it was difficult to generalize the results of the study to the US population.

Due to the relatively specialized indication for nasopharyngeal carcinoma, toripalimb and penpulimab could still be approved. If they do, it will provide additional information on how the FDA can treat other anti-PD- (L) 1 data from China only.

Thanks to an American bridging study that complements two Chinese studies, Huchmed should avoid some uncertainty about homogeneous groups of patients when surufatinib gets ahead of the FDA.

Surufatinib, a treatment for pancreatic and extrapancreatic neuroendocrine tumors (NET), has also shown impressive efficacy, with two key Chinese studies terminating almost due to efficacy. The company’s claim that surufatinib can treat NETs produced by any organ, if true, could give Pfizer Sutent and Novartis Afinitor some competition, as they are only effective in 70% of NET patients.

A green light would mark Hutchmed’s first approval outside China. The only problem may be the FDA’s ability to complete production inspections, an obstacle that has tripped companies like UCB and Sol-Gel, which are now seeking approval for Bimzelx and Epsolay.

Panel pain?

The FDA’s advisory committees will be busy this month, with the first task being to look at Covid’s preparedness. Although the adcom will not discuss or vote on specific vaccine applications, the recommendation for an extended fourth revaccination or vaccine for Omicron variants will be a bonus for Modern and Pfizer.

In contrast, a review of the PI3K-delta class, which has taken data from April’s adcom U2 and Ukoniq from TG Therapeutics, is unlikely to produce good news for those affected. The FDA will investigate Ukoniq’s approved lymphoma settings, as well as its worrying lack of survival benefits in combination with ublituximab in chronic lymphocytic leukemia.

For the broader class of PI3K-delta inhibitors, many have been granted accelerated approval based on single-arm studies. The agency will now decide whether randomized data should be the standard for approval, and zandelisib MEI has already rejected it.

The tables below list the first and subsequent US approval decisions, as well as the Advisory Committee meetings to be held next month, with consensus forecasts from Evaluate Pharma.

The remarkable first US approval decisions to be taken in April
Project Company Pdufa date Indications 2026e sales by indication (SBI) ($ m) Note
Tuoyi (toripalimab) Coherus / Shanghai Junshi April Nasopharyngeal carcinoma (NPC) Anti-PD-1 MAb, Tuoyi + chemo for 1 l NPC and monotherapy for 2 l + NPC
BXCL501 Bioxcel April 5 Agitation associated with schizophrenia and bipolar I and II disorders 378 Late since January, the FDA has asked to analyze clinical data
Vutrisiran Alnylam April 14 Transthyretin-mediated inherited amyloidosis polyneuropathy (hATTR). 1 828 * Subcutaneous continuation after Onpattro, Helios-A-based administration
mavacamten Bristol Myers Squibb April 28 Obstructive hypertrophic cardiomyopathy 1 672 Delayed since January due to updates proposed by REMS
AXS-07 Axsome April 30 Acute migraine treatment 128 Combination of rizatriptan and meloxicam Cox-2 NSAIDs
Sulanda
(surufatinib)
Hutchmed April 30 Pancreatic and non-pancreatic neuroendocrine tumors 362 If approved, it would be Hutchmed’s first cancer drug marketed outside China
Tapinarof Dermavant Q2 Psoriasis plaque
Annik
(penpullimab)
Akeso / Sino Eastern H1 3L nasopharyngeal carcinoma See text
Bimzelx UCB H1 Psoriasis plaque 952 The decision was delayed in October due to Covid’s travel restrictions
Epsolay Left – Come Awaiting processing Papulopustular rosacea The pre-approval inspection was scheduled for mid-February
FT218 Avadel Awaiting processing Narcolepsy 321 Delay in oct
SH-111 Shorla Oncology (private) Awaiting processing T-cell leukemia FDA filing received in April 2021
* SBI as amyloidosis. Source: Company Statement & Evaluate Pharma.
Advisory Committee meetings in April
Project Company Adcom date Indication 2026e sales by indication (SBI) ($ m) Note
Vaccination against Covid-19 No product-specific applications will be discussed April 6 Covid-19 prevention It will discuss the use of Covid booster doses and the vaccine strain selection process to address current and new variants.
PI3K inhibitor class ON THE* April 21 Hematological malignancies It is discussed whether randomized data should be required (MEI suffers from FDA brake on accelerated approval)
U2, Ukoniq TG Therapeutics April 22 Hematological malignancies 1 188 Will discuss U2 for CLL or SLL and the existing Ukoniq accelerated path for y / y FL and MZL
* No details were provided as to whether specific products would be discussed. Source: FDA adcom calendar & Evaluate Pharma.
Complementary and other significant approval decisions to be taken in April
Product Company Indication (clinical trial) A date
Vaxneuvance Merck Prevention of invasive pneumococcal disease in children aged 6 weeks to 17 years (15-valent conjugate vaccine, PNEU-PED) April 1
Yescarta Gilead 2 l large B-cell lymphoma (Zuma-7) April 1
Rain The
(Ronapreve)
Regeneron Treat Covid in non-hospitalized patients and as prophylaxis April 13 (already has EUA)
Aliqopa (kopanlisib) + rituxan Bayer Recurrent indolent B-cell non-Hodgkin’s lymphoma (Chronos-3) East April 21
Qelbree Supernus ADHD in adults (P306) April 29
Ultomiris Astrazeneca Generalized myasthenia gravis (NCT03920293) Q2
Enhertu Astra / Daiichi Her2 + in Breast Cancer After Anti-Her2-Therapy (Destiny-Breast 03) Q2
Olumiant Lilly Treatment of some hospitalized patients with Covid Q2 (already has EUA)
Olumiant Lilly Atopic dermatitis (Breeze-AD) Awaiting processing
Rinvoq Abbie Ankylosing spondylitis Awaiting processing
Kymriah Novartis 3L FL (ph2 Elara) Awaiting processing
Source: Company Statement & Evaluate Pharma.

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