2021 has already seen a number of notable clinical catalysts read out. These include positive Phase II data for Eli Lilly’s investigational Alzheimer’s disease therapy donanemab but also decidedly mixed results for Sarepta’s experimental Duchene muscular dystrophy (DMD) gene therapy SRP-9001.
Here, we take a closer look at a number of other clinical and regulatory catalysts on our radar in the first quarter…
Entresto – heart failure (Novartis)
Entresto is approved to treat heart failure with reduced ejection fraction (HFrEF) and is on track to generate global sales of $2.5 billion for 2020. Novartis estimates that expanded approval to include the treatment of heart failure with preserved ejection fraction (HFpEF) will help to expand sales to around $5 billion by 2025. Entresto narrowly missed the primary endpoint in a HFpEF Phase III study but an FDA advisory committee has voted in favour of recommending approval (possibly with a narrower label), which the agency is expected to ratify before the end of March.
Opdivo + Cabometyx – renal cell carcinoma (BMS/Exelixis)
Bristol Myers Squibb expects its Opdivo franchise to return to growth in 2021, helped in part by approval – in combination with Exelixis’ tyrosine kinase inhibitor (TKI) Cabometyx as a first-line treatment for renal cell carcinoma. The FDA is expected to make an approval decision on or before February 20. Our survey of 120 oncologists last year suggests this combination will become a leading treatment regimen.
Aducanumab – Alzheimer’s disease (Biogen/Eisai)
Whether or not the FDA chooses to approve aducanumab on or before its March 7 PDUFA date remains in the balance, despite an advisory committee to the agency recommending against approval in November. Speaking at the recent JP Morgan Healthcare Conference, Biogen management expressed surprise at the AdCom’s recommendation and appeared bullish that approval is in the offing. Discussions are reportedly ongoing about a potential label for aducanumab – is this a sign that the FDA is willing to overrule the experts and what impact will Eli Lilly’s recent data for donanemab have on proceedings?
See KOL Views Q&A: Eli Lilly's donanemab win suggests anti-beta amyloid mAbs may be inevitable, according to leading expert and KOL Views Q&A: Leading neurologist lays out scenarios for after FDA decides on aducanumab
Casimersen – DMD (Sarepta)
Sarepta will hope than pending US approval of casimersen – on or before February 25 – will offset some the disappointment associated with its DMD gene therapy programme. Casimersen could potentially be used to treat around 10% of DMD patients (those who have genetic mutations that are amenable to skipping exon 45 of the dystrophin gene). The clinical benefits seen with casimersen are relatively modest but this has not prevented the FDA approving Sarepta’s other DMD therapies Exondys 51 and Vyondys 53, or these becoming well established therapies for certain patients with DMD. If Sarepta can overcome the challenges presented with its gene therapy, its established position in the DMD market could prove critical.
Ide-Cel – multiple myeloma (BMS)
The FDA is expected to approve Ide-Cel on or before March 27, in the process introducing CAR-T therapy into the treatment paradigm for multiple myeloma. If approved, Ide-Cel would also become only the second approved therapeutic which targets BCMA, after GlaxoSmithKline’s Blenrep (an antibody drug conjugate which was approved by the FDA for the treatment of multiple myeloma last year). Co-developed by bluebird bio and Celgene (acquired by BMS for $74 billion two years ago) Ide-Cel’s path to market has not been completely straightforward, with the FDA rejecting an initial application and requesting additional manufacturing data last May. Competition is also likely to be intense once Ide-Cel has reached the market, from other CAR-T therapies (such as Johnson & Johnson’s Cilta-cel) and bispecific monoclonal antibodies, say experts.
Sotorasib – NSCLC (Amgen)
Amgen’s sotorasib, a potential first-in-class KRAS inhibitor, has already been filed with the FDA for the treatment of certain lung cancer patients but the Phase II data submitted as part of this application has yet to be revealed publicly. Results will be presented at the forthcoming World Congress on Lung Cancer (WCLC) meeting at the end of the month. If approved, sotorasib is expected to quickly become a new standard of care second- and third-line therapy for the approximate 15% of non-small cell lung cancer (NSCLC) patients who have a KRAS G12C mutation. With a competitor from Mirati Therapeutics also in development, first-to-market status could be critical for Amgen, as will subsequent combination data readouts with other cancer drugs.
Relatlimab + Opdivo – melanoma (BMS)
A Phase II/III (registration-supporting) study is underway evaluating Opdivo in combination with the potential first-in-class LAG-3 inhibitor relatlimab for the first-line treatment of melanoma. Positive data would potentially transition relatlimab into a platform immuno-oncology drug for BMS and trigger studies in other tumour types. Experts are sceptical that the combination with better results seen with the already-marketed Opdivo/Yervoy combination.
SAGE-324 – essential tremor (Biogen/Sage)
Given the binary nature (and heightened stakes) of the FDA’s pending approval decision for aducanumab, Biogen sought to diversify its mid- to late-stage pipeline late last year through a deal with Sage Therapeutics. The main focus on this co-development/marketing collaboration is the investigational depression therapy zuranolone, with Phase III data expected to read out later in 2021. The first quarter should see Phase II data unveiled for SAGE-324 in essential tremor and could shape early-year sentiment towards the value of Biogen’s collaboration with Sage.
Polivy DLBCL (Roche)
Polivy remains something of an overlooked asset despite its strong launch in relapsed diffuse large B-cell lymphoma (DLBCL) patients and positive data in the POLARIX study (in combination with Rituxan and chemotherapy) would significantly expand its commercial potential by moving it into the first-line setting. As Roche looks to further expand its role in this segment with bispecific antibodies, Polivy stands to become not only an important franchise in its own right but a potentially important combination therapy.
Deucravacitinib – psoriasis (BMS)
Positive top-line data (versus Amgen’s Otezla) from the first in a series of Phase III studies has significantly de-risked the outlook for deucravacitinib, a potential first-in-class, oral, Tyk-2 inhibitor for psoriasis. Bristol Myers Squibb is in bullish mood, suggesting sales will reach at least $4 billion by 2029. Data from a second Phase III study – expected in Q1 – will help to validate this outlook.
Etranacogene dezaparvovec – haemophilia B (CSL/UniQure)
News flow for etranacogene dezaparvovec, an investigational gene therapy for haemophilia B being co-developed by CSL and UniQure, ended 2020 on something of a rollercoaster ride. Positive initial Phase III data (evaluating use up to 26 weeks) was presented in November, before the FDA placed evaluation under clinical hold in December after a case of hepatocellular carcinoma (HCC) "possibly related" to etranacogene dezaparvovec was diagnosed in a trial participant. If this challenge can be overcome (see ViewPoints: Haematologist says uniQure’s gene therapy hold not cause for panic) US approval could be secured on the strength of 52-week data, which should arrive in Q1.
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