ASH in review
Taking the form of a virtual event this year, the annual meeting of the American Society of Hematology (ASH) took place earlier this week, providing the platform for exciting new developments in the fields of sickle cell disease, haemophilia A and B, and various haematological cancers. See our analysis of key data readouts below.
With ASH the last major medical meeting of 2020 it remains to be seen how the conference landscape evolves in 2021. Speaking to FirstWord on the (virtual) side-lines of ASH this week, Genmab CEO Jan van de Winkel said that thanks to the advent of COVID-19 vaccines, he is hopeful that some in-person medical meetings will take place in the second half of next year.
To what extent these events will resemble the major medical meetings of the past, initially at least, remains to be seen. "I'm not sure you are going to see 25,000 haematologists and oncologists from all over the world running around at ASH next year," says van de Winkel, who believes that in-person events will take place, but will be limited to a smaller number of attendees. Hopefully this 'new normal' will be temporary and medical meetings will be scaled up to allow more attendees in 2022 and beyond, predicts the Genmab CEO.
Look out for further analysis, including Physician Views survey and KOL Views content, over the next week.
The beginning of the end?
On the subject a slow return to normality, the first people to be vaccinated with BioNTech and Pfizer's BNT162b2 outside of a clinical trial received the vaccine in the UK on Tuesday.
This coincided with the release of briefing documents published by the FDA ahead of an advisory committee meeting scheduled for Thursday to discuss BioNTech and Pfizer's application for emergency-use authorisation (EUA) in the US. The documents, which summarise the agency's review of BNT162b2, further emphasise just how effective the vaccine is. A second AdCom meeting to discuss Moderna's vaccine mRNA-1273 is scheduled to take place next week. Like BNT162b2, mRNA-1273 is both an mRNA-based vaccine and has demonstrated approximately 95% effectiveness at preventing symptomatic COVID-19.
By comparison, the adenovirus vector vaccine AZD1222, which is being co-developed by AstraZeneca and the University of Oxford, appears to be moderately effective at preventing symptomatic COVID-19 in 62% of cases. AZD1222 will cost less and can be much more easily distributed, stored and administered, however, suggesting that its role in the vaccine-response could be heavily determined by its effectiveness at preventing severe cases of COVID-19 including those requiring patient hospitalisation.
Data, now peer reviewed in The Lancet, suggests this is the case, but no further light has been shone on why a subset of patients who accidently received a half-sized priming dose of AZD1222 appeared to be at much lower risk of contracting COVID-19. AstraZeneca said this week it is undecided whether to run a larger study evaluating this dosing regimen to see if it can replicate the 90% effectiveness rate seen in a small cohort of around 3000 patients.
Eli Lilly’s tirzepatide reveal
Eli Lilly investors have been eagerly anticipating initial Phase III data for the company's diabetes treatment tirzepatide, a potential first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. Expectations (and sales forecasts) have been raised by impressive Phase II data that were released in 2018.
Results from the first of five ongoing Phase III trials, which were top-lined by Eli Lilly on Wednesday, show impressive glucose lowering and weight reduction versus placebo coupled with an acceptable tolerability and side-effect profile.
Those expecting data strong enough to show clear superiority over GLP-1 agonists, including Novo Nordisk's Ozempic and Eli Lilly's Trulicity, may be disappointed. That said, head-to-head data versus the former is due to read out early next year and could prove more conclusive in shaping the future competitive landscape.
The expert view on aducanumab
Biogen is waiting to hear whether the FDA will overlook the advice of experts (convened at a recent AdCom meeting) and approve its investigational Alzheimer's drug aducanumab. Assuming a decision is not announced by year-end, biotech investor focus is likely to be remain sharpened on this regulatory outcome in the early weeks (and potentially months) of 2021.
That the agency could still approve aducanumab is testament to the nuances of this particular regulatory decision and reflective of its own (seemingly positive) assessment of the drug and what appears to be close co-operation in supporting Biogen's regulatory application.
FirstWord hosted a live discussion for FirstWord Pharma PLUS subscribers with Joshua Grill, associate professor and director of the Institute for Memory Impairments and Neurological Disorders at the University of California Irvine, wherein we discussed the potential real-world impact for patients, prescribers and drug developers depending on what verdict the FDA eventually renders.
PLUS users can read a follow-up article here: KOL Views Q&A: Leading neurologist lays out scenarios for after FDA’s decides on aducanumab.
In the meantime, Biogen and its partner Eisai have announced they are also seeking Japanese approval of aducanumab for the treatment of Alzheimer's disease.
Biogen recently announced a deal to co-develop a number of novel assets with Sage Therapeutics for depression and the movement disorder essential tremor, viewed by many as a potential hedge against a negative regulatory outcome for aducanumab. Our short survey of primary care physicians and psychiatrists indicates that the drugs included under this arrangement could meet significant levels of unmet need, assuming of course that Phase III data are positive.
Amgen nears KRAS filing
Having confirmed that it is on track to submit its cancer drug sotorasib to the FDA by the end of the year, Amgen looks well positioned to bring a first-in-class KRAS inhibitor to market in 2021. KRAS was long considered to be an 'undruggable' target following its identification by scientists more than 40 years ago. Approval would therefore be a big win for Amgen's credentials in cancer drug development.
Amgen is specifically seeking approval as a second-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) who harbour a KRAS G12C mutation, which are estimated to occur in around 14% of all NSCLC patients.
Amgen hopes that approval next year represents the first step to establishing sotorasib as a "foundational" therapy for NSCLC and, potentially in time, other tumour types where the KRAS G12C mutation is present. Efforts are under way to evaluate sotorasib with other cancer medicines, including checkpoint inhibitors.
Achieving this regulatory benchmark will also put Amgen someway ahead of Mirati Therapeutics, its closest competitor in the KRAS inhibitor field. They anticipate submitting their drug – adagrasib – for a similar indication later in 2021.
With our recent survey of lung cancer specialists showing that awareness and enthusiasm for the KRAS inhibitor class is high, first-to-market status for Amgen could be critical in allowing it to meet commercial expectations.
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