Go or no go? Pdufa resolutions eyed for J&J and Amryt
February will also see an outcome for Gilead's long-acting HIV therapy, and a key FDA panel for me-too checkpoint MAbs.
Several projects with delayed Pdufa decisions should finally see outcomes next month, including J&J/Legend's ciltacabtagene autoleucel and Amryt’s Oleogel-S10. Immunocore, however, was able to grasp an early approval today for its immunotherapy tebentafusp, now called Kimmtrak, nearly a month before its February Pdufa decision.
One of the most important regulatory discussions in February will come from a panel meeting on Lilly and Innovent’s Tyvyt. The adcom could indicate whether data generated in China can back US approval.
Tyvyt’s China study, Orient-11, tested the anti-PD-1 MAb in combination with chemotherapy in first-line non-squamous NSCLC. While the results showed a survival benefit the comparator was chemo alone and not Keytruda − the Merck & Co drug that is redefining front-line NSCLC therapy, based on the Keynote-189 study.
If the regulators decide that head-to-head US studies are needed here Tyvyt, and others relying on China data, could be in for long delays (Days of reckoning for immune checkpoint blockers, January 4, 2022).
Three months later...
J&J/Legend’s BCMA-targeted Car-T project cilta-cel should finally get a decision next month; its original Pdufa date was November, but this was pushed back to give the FDA time to review new information on "an updated analytical method following an FDA information request", according to J&J.
Cilta-cel has demonstrated a strong clinical profile in heavily pretreated multiple myeloma patients, and boasts better efficacy on a cross-trial basis than Bristol Myers Squibb/Bluebird's Abecma, which was approved for fifth-line use last year.
Cilta-cel's label will likely echo Abecma’s, which includes a black box warning of haemophagocytic lymphohistiocytosis/macrophage activation syndrome and cytopenia, in addition to the cytokine release syndrome and neurotoxicities that are standard with Car-T therapies.
Also suffering a delay was Amryt’s epidermolysis bullosa project Oleogel-S10, with the regulators needing extra time to review additional data analyses.
Despite the delay Oleogel-S10, a topical gel formulation of the plant extract betulin, could still become the first therapy for the rare skin disorder, but Krystal Biotech is gaining ground. Krystal’s topical gene therapy Vyjuvek is expected to be filed in the first half of the year; the asset recently yielded promising topline data, although there are still unanswered questions.
Meanwhile, Gilead’s lenacapavir could become the first capsid inhibitor approved for HIV, and the only treatment given every six months. A green light is likely by the end of next month in heavily pretreated patients, but a push into earlier treatment lines will be key to this project's chances of generating big bucks.
The phase 2/3 Capella study found that 88% of lenacapavir-treated patients achieved a clinically meaningful viral load reduction of at least 0.5log10 copies/ml, versus 17% of patients receiving placebo. Here the focus was heavily treatment-experienced patients with multidrug-resistant HIV who were failing on antiretroviral drugs (Gilead challenges Viiv in heavily treated HIV, March 10, 2021).
Viiv’s Rukobia is already approved in heavily treatment-experienced patients, but is given as a twice-daily tablet.
Phase 3 trials with lenacapavir in pre-exposure prophylaxis have already started. However, these and other studies were put on clinical hold in December owing to vial contamination concerns.
And Viiv again is one step ahead with Apretude – the extended-release version of cabotegravir got the green light in December for Prep, where it is given every two months after an initial loading dose.
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 February
|2026e sales by indication ($m)
(immune globulin intravenous, 10% liquid)
|Primary humoral immunodeficiency
|Gained EMA approval back in 1997, filed in the US in Aug 2021
|Feb 2 (resubmitted)
|Haemolysis in adults with cold agglutinin disease
|Previous CRL due to deficiencies at manufacturing facility
|Pyruvate kinase deficiency
|Also in development for thalassaemia and sickle cell disease
|Negative adcom in December
|d-amphetamine transdermal system
|Est Feb 25
|Junctional and dystrophic epidermolysis bullosa
|Extended from Nov by submission of additional analyses
|Johnson & Johnson/
|3L+ multiple myeloma
|Extended from Nov by info request on analytical method
|Myelofibrosis patients with severe thrombocytopenia
|Extended from Nov after new of data submission
|Multidrug-resistant HIV in heavily treatment-experienced patients
|3L nasopharyngeal carcinoma
|Days of reckoning for immune checkpoint blockers
|Radioligand therapy for mCRPC
|Asco 2021 justifies Novartis’s radioligand Vision
|*Forecasts made before Dec adcom. Source: Evaluate Pharma & company releases.
|Advisory committee meetings in February
|Tyvyt (sintilimab) +
|1L stage IIIB, IIIC, or Stage IV non-squamous NSCLC
|Days of reckoning for immune checkpoint blockers, Pdufa in March
|Tentatively scheduled, notified in PR but no official notice on FDA website, two previous CRLs
|Amend the EUA for administration to children 6 months through 4 years of age
|Already authorised for use in children aged 5-11 years, also as a single booster dose in individuals 12-15 years and older
|Source: Evaluate Pharma & FDA adcom calendar.
|Supplementary and other notable approval decisions in February
|Indication (clinical trial)
|r/r FL after two prior lines of treatment (Ph2 Elara)
|Est Feb 25
|Adjuvant BRCA-mutated Her2-negative breast cancer (OlympiA)
|Atopic dermatitis (Breeze-AD programme)
|Ankylosing spondylitis and ulcerative colitis
|Source: Evaluate Pharma & company releases.