This week Eli Lilly received FDA emergency-use authorisation (EUA) for a neutralising antibody cocktail combining bamlanivimab with etesevimab, to treat mild-to-moderate COVID-19 in patients who are at high risk for progressing to severe disease and/or hospitalisation. Last month, Eli Lilly reported that administering the combination therapy reduced COVID-19-related hospitalisations and deaths by 70% in a Phase III trial of recently infected, high-risk patients.
The company recently estimated that sales of COVID-19 neutralising antibody products could reach $2 billion in 2021, with at least half of that revenue likely to be recognised during the first quarter (after which vaccine use is expected to diminish COVID-19 therapeutic sales).
In terms of vaccine updates, a small study has shown that AZD1222, the COVID-19 vaccine developed by AstraZeneca and the University of Oxford, may offer minimal protection against mild and moderate disease caused by the B.1.351 coronavirus variant, which is thought to have originated in South Africa. It is hoped that AZD1222 will prevent severe disease. Vaccines developed by Moderna, BioNTech/Pfizer, Novavax and Johnson & Johnson all appear to be less effective against this variant.
Echoing use of AZD1222 at the front and centre of the UK’s vaccination programme, the World Health Organization's (WHO) Strategic Advisory Group of Experts on Immunization (SAGE) this week recommended use of the vaccine in individuals 18 years and over, with a preferred dosing interval of eight to 12 weeks.
Merck & Co.'s development and regulatory programme for the cancer immunotherapy Keytruda has largely been one of exemplary execution over the best part of the previous decade. As a result, the drug generated an eye-watering $14.4 billion in sales last year.
Events over the past week have shown, however, that challenges exist even for cornerstone therapeutics such as Keytruda, particularly with regard to potential use in earlier-stage disease. Companies that are heavily invested in the PD-(L)1 inhibitor class to which Keytruda belongs are running a catalogue of clinical studies to demonstrate the effectiveness of these agents as neoadjuvant and adjuvant therapies across multiple tumour types. The commercial rewards could be significant.
This week Merck's efforts to secure approval for Keytruda as a treatment for earlier-stage triple-negative breast cancer (TNBC) were under the spotlight and appear, temporarily at least, to have hit a brick wall. A panel of experts convened by the FDA voted unanimously to suggest that an increase in pathological complete response alone provides insufficient clinical evidence to warrant approval of Keytruda as a neoadjuvant therapy for TNBC. Merck has been told it must wait for event-free survival data to mature.
Unlike earlier studies of the checkpoint inhibitors in metastatic disease, which frequently produced usable clinical data earlier than expected, trials evaluating neoadjuvant and adjuvant use are likely to take longer.
A frustrating wait for these data in certain earlier-stage cancers, which are robust enough to appease regulators, is enhanced by adjuvant approvals already in some tumour types (melanoma) and clear signs of efficacy in others.
This weekend at the ASCO-GU meeting, for example, new data will be presented for Bristol Myers Squibb's competing PD-(L)1 inhibitor Opdivo showing that it significantly improved disease-free survival (DFS) when used as an adjuvant treatment for surgically resected, high-risk muscle invasive bladder cancer. In all patients evaluated, Opdivo was shown to nearly double the average length of time patients lived without disease recurrence, demonstrating a median DFS of 21 months versus 10.9 months for placebo, or a risk reduction of 30%. Detailed results will be presented on February 12.
CheckMate-274 is the first positive Phase III trial evaluating an immunotherapy in the adjuvant setting of muscle-invasive urothelial carcinoma and Opdivo has now demonstrated clinically meaningful efficacy as an adjuvant treatment in four tumour types (the others being melanoma, oesophageal and non-small-cell lung cancer).
Elsewhere at ASCO-GU, oncologists and investors will get their first view of detailed results from the CLEAR study evaluating Keytruda plus Eisai's Lenvima in first-line renal cell carcinoma (RCC). An abstract released ahead of the meeting suggests the combination is potent, but may be associated with more adverse events than other immunotherapy-based regimens that are already approved in the crowded first-line RCC market.
With the JAK inhibitor market already worth billions of dollars and forecast to expand significantly due to new launches in this drug class, the recent disclosure that Pfizer's first-to-market agent Xeljanz has been linked to new safety concerns (increased risk of cardiovascular side-effects and malignancies versus TNF inhibitors) is a cause of some concern.
This week FirstWord spoke to a leading rheumatologist who predicts the new data will result in an even starker black-box warning being added to Xeljanz's label. Thereafter, it may be a case of the JAK class "being guilty until proven innocent," he suggests, putting onus on the manufacturers of competing products to demonstrate greater selectively and fewer safety concerns. More here.
In April, dermatologists will get their first view of detailed Phase III data for Bristol Myers Squibb's oral Tyk-2 inhibitor deucravacitinib in moderate-to-severe psoriasis. We know that in two pivotal-stage studies it has bested Amgen's Otezla, the only available oral treatment. Phase II results suggest that deucravacitinib may be significantly more efficacious and if so, results from our new survey of 115 dermatologists (based in the US and Europe) suggests that uptake at the expense of Amgen's drug could be swift.
To read more Friday Five articles, click here.