Go or go go? J&J’s cell therapy heads to the FDA
November approval decisions loom for cilta-cel and Voxzogo, while molnupiravir heads for an advisory panel.
Johnson & Johnson's ciltacabtagene autoleucel could soon become the second approved cell therapy for multiple myeloma, with its Pdufa date falling towards the end of next month. The BCMA-targeted Car-T therapy is gunning to take on Bristol Myers Squibb/Bluebird's Abecma, and boasts better efficacy.
Elsewhere, Biomarin is taking its achondroplasia project back to the regulators after submitting durability data, while a panel will decide whether molnupiravir, Merck & Co/Ridgeback’s oral Covid-19 antiviral, has safety in hand.
Second place, but for how long?
Cilta-cel’s filing was based on Cartitude-1, an open-label study in relapsed/refractory multiple myeloma patients who had received at least three prior lines of therapy or were double-refractory to a proteasome inhibitor and immunomodulatory drug.
Efficacy reported at this year’s Asco was impressive, with the overall response rate in 97 patients hitting 98%, including an 80% complete response rate and median progression-free survival of nearly 23 months.
Abecma’s label also includes a black box warning of haemophagocytic lymphohistiocytosis/macrophage activation syndrome and cytopenia, in addition to the cytokine release and neurotoxicities that are standard with Car-T therapies. Cilta-cel will probably contain a similar warning, and has been associated with higher neurotoxicity than Abecma.
Greater opportunity lies in earlier lines of therapy, but toxicity could hold up both Abecma and cilta-cel.
Durability still a question
In August Biomarin’s vosoritide, now called Voxzogo, became the first medicine approved in Europe for the treatment of children aged two and over with achondroplasia. A decision in the US is due in November after a three-month delay.
Biomarin’s original NDA filing included one-year phase 3 data in children over five years old given daily injections of Voxzogo. The FDA, however, expressed a desire for two-year controlled data to ensure that the efficacy of Voxzogo was durable. In Europe one-year data had been enough for approval.
Additional data from the open-label extension study were subsequently submitted to the US regulator, though this did not include a direct placebo-controlled comparison. Durability was shown through a comparative analyses of participants randomised to the active arm versus participants on placebo with two years' untreated follow-up.
Voxzogo is forecast to become the top-selling achondroplasia project in 2026, according to Evaluate Pharma consensus. Ascendis’s Transcon CNP, the most advanced rival, is still only in phase 2. But Ascendis is going for convenience, testing once-weekly treatment, with an update from two placebo-controlled trials due this quarter.
Safety will likely dominate the discussion at a November 30 US adcom for Merck & Co and Ridgeback’s molnupiravir. The oral antiviral yielded impressive results last month in Covid-19 outpatients, but some concern has been voiced over its potential for mutagenicity.
Molnupiravir works by causing a large number of genetic mutations in the replicating virus, and the worry is that mutations might also occur in the RNA of patients who take it, though Merck insists that it has not found anything worrying.
If given backing, and a subsequent approval, molnupiravir offers convenience advantages versus infused antibodies. Another phase 3 study, Move-Ahead, in post-exposure prophylaxis is due to report next year.
The tables below list first-time and supplementary US approvals, as well as advisory committee meetings due next month, with consensus forecasts from Evaluate Pharma.
|Notable first-time US approval decisions due in November|
|Project||Company||PDUFA date||Indication(s)||2026e sales by indication ($m)||Note|
|Laboratorios Farmacéuticos Rovi||Est Nov||Schizophrenia||376||Long-acting injectable|
(pafolacianine sodium injection)
|On Target Laboratories||Est Nov 3||Adjunct for identifying ovarian cancer during surgery||–||Binds to folate receptors and illuminates intraoperatively under near-infrared light|
|Topiramate oral solution
|Azurity/ Eton||Nov 6||Tonic-clonic seizures, partial-onset seizures, and as preventative treatment of migraine||–||Extended from Aug|
(treprostinil inhalation powder)
|Pulmonary arterial hypertension||126||Previous CRL for CMC issues|
|Besremi (ropeginterferon alfa-2b)||Pharmaessentia||Nov 13
|Polycythemia vera||–||Previous CRL due to manufacturing inspection delay|
|Maribavir||Takeda||Est Nov 19||Post-transplant cytomegalovirus infection in refractory pts with/without resistance||354||Backed by adcom in October|
|Biomarin||Nov 20||Achondroplasia||720||See text|
|Aadi Bioscience||Nov 26||Advanced malignant PEComa||–||Nab-sirolimus|
|Cisplatin-induced ototoxicity for paediatric patients||165||Previous CRL (CMC)|
|Nov 29||3L+ multiple myeloma||1,692||See text|
|CTI Biopharma||Nov 30||Myelofibrosis patients with severe thrombocytopenia||368||Oral kinase inhibitor with specificity for Jak2, Irak1, and CSF1R|
|Plinabulin + G-CSF||Beyondspring||Nov 30||Prevention of chemotherapy-induced neutropenia||138||Also being tested in NSCLC, but data were unimpressive (Esmo 2021 – Beyondspring experiences winter of discontent)|
|Nov 30||Hepatitis B||164||3-antigen hepatitis B vaccine|
|Amryt||Nov 30||Epidermolysis bullosa||285||Could become the first approved treatment (Epidermolysis bullosa gene therapies wait in the wings)|
|Pfizer||Q4?||Atopic dermatitis||1,035||Timings to be confirmed; with the FDA's recent safety review of the class approval could include suboptimal dosing and black box warnings|
|Epsolay||Sol-Gel||Q4?||Papulopustular rosacea||–||Delayed in April as Covid-19 travel restrictions prevented pre-approval inspection|
|Takeda||Q4?||Eosinophilic esophagitis||187||April Pdufa missed|
|CMC=Chemistry, manufacturing and controls. Source: Evaluate Pharma & company releases.|
|Advisory committee meetings in November|
|Project||Company||Adcom date||Indication||2026e sales by indication ($m)||Note|
|Levo||Nov 4||Hyperphagia, anxiety, and distress behaviours associated with Prader-Willi syndrome||–||Pdufa expected by YE|
|Nov 30||EUA for the treatment of mild to moderate Covid-19 in adults who are at risk for progressing to severe Covid-19 and/or hospitalisation||–||See text|
|Source: FDA adcom calendar & Evaluate Pharma.|
|Supplementary and other notable approval decisions in November|
|Product||Company||Indication (clinical trial)||Date|
|Bio-Thera Solutions||Colorectal cancer (+ chemo), 1L non-squamous NSCLC, recurrent glioblastoma, renal cell carcinoma (+ interferon alfa), cervical cancer||Nov 27|
|Xeljanz||Pfizer||Ankylosing spondylitis (A3921120)||Q4?|
|Olumiant||Lilly||Atopic dermatitis (Breeze-AD programme)||Q4?|
|Rinvoq||Abbvie||Atopic dermatitis, psoriatic arthritis and ankylosing spondylitis||Q4?|
|Source: Evaluate Pharma & company releases.|