FDA in focus
Has the FDA suddenly become more conservative in its attitudes to new drug approvals?
There is a growing school of thought that it has, with advocates pointing to recent regulatory updates provided by FibroGen, Acadia and Kadmon, all of which face unexpected delays as a result of the agency wanting to review additional data or run it by independent experts.
This week Roche also announced that it has withdrawn its PD-L1 inhibitor Tecentriq from the US market as a treatment for second-line bladder cancer following discussions with the FDA.
This is the third checkpoint inhibitor indication granted on an accelerated approval basis, but subsequently not confirmed by pivotal-stage data, to be withdrawn in recent weeks.
In major news, the FDA announced on Thursday that it will convene a three-day advisory committee meeting in April to review a number of additional cases where checkpoint inhibitors remain on the market (as a result of accelerated approval) despite negative confirmatory studies.
It is worth noting, of course, that the agency is currently without a permanent commissioner and President Biden is under pressure from previous holders of this role to appoint one as soon as possible.
Janet Woodcock is serving as the interim commissioner and may resume the role permanently. She is closely associated with the agency's lenient approach towards certain drug approvals in recent years, most notably Sarepta's Duchene muscular dystrophy (DMD) treatment eteplirsen.
Perhaps she is seeking to redress the balance.
Canakinumab fails in second-line lung study
Novartis' anti-inflammatory agent canakinumab failed to show a survival benefit in second- and third-line non-small-cell lung cancer (NSCLC), diminishing its chances of success in two other ongoing pivotal-stage studies for first-line and adjuvant NSCLC.
Its best chance may be in the latter, argue some analysts.
Adjuvant use would most closely mirror the design of CANTOS, a Phase III study Novartis previously ran to evaluate canakinumab as a treatment for atherosclerosis. This trial failed, but post-hoc analyses suggested the drug reduced the chances of patients developing lung cancers.
Novartis took a big chance by moving canakinumab directly into a broad pivotal-stage lung cancer programme. The outlook is looking increasingly risky.
With focus sharpened on the FDA's current attitude to new drug approvals (see FDA focus, above), it would be remiss not to consider the potential impact on Biogen and Eisai's investigational Alzheimer's disease treatment aducanumab.
Having extended its review of the drug by three months earlier this year, the agency is expected to make a decision on approval by June.
Any outcome may be swayed by emerging data for similar therapies such as Eli Lilly's donanemab, which will be under the spotlight at this weekend's virtual AD/PD 2021 meeting.
Positive top-line Phase II data weres announced by Eli Lilly in January and detailed results will be presented on Saturday.
This raises the question as to whether Eli Lilly could even file donanemab on the strength of a smaller, mid-stage study. Robust data will increase hopes that it can, even if the FDA appears to be moving in a more conservative direction.
Bluebird investors, gene therapy field breathes tentative sign of relief
Bluebird bio concluded that it is very unlikely that its gene therapy LentiGlobin caused the development of acute myeloid leukaemia (AML) in a patient who received the treatment for sickle cell disease (SCD) five years ago.
The site of vector insertion occurred in a gene (VAMP4) with no known role in oncogenesis, the company said. Bluebird bio also noted that the vector for LentiGlobin was identified in blast cells from the AML patient, suggesting that a busulfan conditioning regimen was also unlikely to blame.
This appears to be an important step towards exonerating bluebird bio's product and platform. However, it still leaves investors wanting an explanation about a second patient who is thought to have developed myelodysplastic syndrome (MDS).
Bluebird bio emphasised this week that the patient has not yet officially been diagnosed with MDS. While a common MDS-like mutation (trisomy 8) has been detected in a fraction of the individual's marrow cells, the preliminary diagnosis was based on prolonged anaemia and no blasts or dysplastic cells – a required feature of the condition – have been found.
Investors were heartened by the new information provided by bluebird bio, which saw its shares jump by 14% on the day leaving its market cap at $2.2 billion.
BioNTech and Pfizer said that real-world data from Israel suggests their COVID-19 vaccine is 94% effective at preventing asymptomatic infection. If accurate, this means it could significantly reduce COVID-19 transmission.
The European Union has granted emergency approval to Johnson & Johnson's COVID-19 vaccine.
Denmark, Norway and Iceland temporarily suspended use of AstraZeneca and the University of Oxford's COVID-19 vaccine while the European Medicines Agency investigates a potential link to blood clots.
Data for Vir and GlaxoSmithKline is an important win for the antibody product VIR-7831, which was recently identified as unlikely to provide a significant benefit to patients already hospitalised with COVID-19 (see ViewPoints: GSK's pandemic bet on Vir falls short). The 85% reduction in risk of hospitalisation seen with VIR-7831 is particularly impressive considering this stems from use as a monotherapy and not as part of a cocktail. That said, questions remain about the commercial viability of antibody treatments, shaped by the effectiveness of vaccines and the logistical challenges of utilising these intravenously administered drugs in an outpatient setting.
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