Friday Five – The pharma week in review (19 February 2021)

COVID watch

Preliminary findings from an in vitro study published Wednesday in the NEJM showed that Pfizer and BioNTech's COVID-19 vaccine BNT162b2 elicited roughly two-thirds lower levels of neutralising antibodies against a highly transmissible SARS-CoV-2 variant that was first spotted in South Africa. However, the authors said it remains "unclear" what such a reduction in neutralisation would have on BNT162b2-induced protection from infections caused by the B.1.351 lineage of the virus. More here

In other news real world data show that two doses of BNT162b2 can cut the number of symptomatic COVID-19 infections by 94%, whilst also reducing severe illness by 92%. 

The European Medicines Agency announced on Tuesday that it has received a conditional marketing application for Johnson & Johnson's COVID-19 vaccine candidate Ad26.COV2.S, and that it intends to review the submission under an accelerated timetable. Pfizer and BioNTech also announced this week that they have agreed to supply an additional 200 million doses of BNT162b2 to the EU, with the European Commission also having the option to request another 100 million doses.

Another competitor in first-line RCC

Detailed results from the Phase III CLEAR study presented at last weekend’s ASCO-GU meeting would appear to position the combination of Merck & Co.’s Keytruda with Eisai and Merck’s Lenvima as an approvable first-line treatment option for advanced renal cell carcinoma.

This market is competitive with three other PD-(L)1 + tyrosine kinase inhibitor (TKI) combinations already approved in the US as well as Bristol Myers Squibb’s dual immunotherapy combination of Opdivo and Yervoy.

Versus rival combinations the pairing of Keytruda and Lenvima does appear to have the most potent efficacy in terms of the number of patients achieving complete response to therapy and on progression free survival. This comes at a cost, however, in terms of some additional toxicity.

KOL Views Q&A: Keytruda/Lenvima's impressive initial efficacy won't necessarily translate to use in 1L RCC, says leading oncologist

Bluebird’s wings get clipped

The clouds which have recently hung over gene therapy drug development landscape got a little darker this week when bluebird bio announced that it has temporarily halted two trials, including a Phase III study, investigating its LentiGlobin gene therapy for sickle cell disease (SCD) when it was confirmed that a patient treated in one of the trials five years ago has developed acute myeloid leukaemia (AML). 

Furthermore, bluebird bio said it is also temporarily pausing marketing of its transfusion-dependent beta-thalassemia therapy Zynteglo in Europe as it is manufactured using the same BB305 lentiviral vector.  Shares in the company fell as much as 34% in response to the announcement.

The disclosure is unfortunately timed, coming just weeks after bluebird bio CEO Nick Leschly unveiled proposals to split the company into two separate business units focused on genetic diseases and oncology.

Speaking to investors and analysts this week Leschly stressed that the company remains committed to the spinoff. However, if bluebird’s investigation fails to exonerate the product, which analysts suggest represents the lion’s share of the SGD unit’s projected value doubts will emerge about how viable it would be as a standalone business.

Data continues to accumulate for Lilly’s tirzepatide

Additional top-line Phase III data for Eli Lilly’s first-in-class GIP/GLP-1 agonist tirzepatide was presented this week largely reinforcing what we know about the investigational diabetes treatment; it is more effective than currently available therapies at lowering blood glucose and body weight.

To what extent this efficacy can be leveraged to gain share the expense of GLP-1 agonists may depend on how manageable endocrinologists determine tirzepatide’s side-effect profile to be. Outstanding efficacy comes partly at the cost of worse gastrointestinal tolerability, including nausea, vomiting and diarrhoea.

Next on the menu are data from a head-to-head study versus Novo Nordisk’s GLP-1 agonist Ozempic, with results expected to read out before mid-year. Positive data here could bolster the launch performance of tirzepatide, assuming it gains approval sometime next year. In the longer-term, however, uptake of tirzepatide may accelerate further if data concludes that Eli Lilly’s drug provides as much of a cardio-protective effect as the GLP-1 agonists. Data from a larger head-to-head study against Eli Lilly’s own GLP-1 Trulicity should answer this conclusively and is due to read out in 2024.

Nektar gets another Big Pharma shot with bempegaldesleukin

Nektar Therapeutics has announced a clinical trial collaboration and supply deal with Merck & Co. to launch a Phase II/III trial testing the investigational CD122-preferential IL-2 pathway agonist bempegaldesleukin in combination with Keytruda. The study, which is slated to get under way in the second half of 2021, will evaluate the combination regimen as a first-line treatment for certain patients with metastatic or unresectable recurrent squamous cell carcinoma of the head and neck (SCCHN). Shares in Nektar gained as much as 13% on the news.

The deal comes despite the somewhat chequered past of bempegaldesleukin. Nektar grabbed headlines in 2018 when Bristol Myers Squibb paid nearly $2 billion for joint development and commercialisation privileges concerning the drug, which the companies set about testing in combination with the PD-1 inhibitor Opdivo and/or CTLA-4 inhibitor Yervoy in a host of solid tumour indications.

Bempegaldesleukin has shown some early promise in a handful of tumour types but largely failed to live up to the lofty expectations implied by Bristol Myers Squibb’s heavy investment. Nektar remains bullish about the programme’s prospects, however, and argues that manufacturing issues may explain a drop-off in efficacy observed in studies evaluating it with a PD-1 inhibitor.

Nektar is fast approaching important inflection points for its Bristol Myers Squibb alliance as pivotal trials evaluating bempegaldesleukin plus Opdivo in bladder, kidney and skin cancer will be reading out soon, and will likely be a crucial arbiter of whether the deal – featuring the eye-popping upfront money – is a dud. This week’s deals indicate that Nektar is not the only one that harbours some belief that the bempegaldesleukin, which the company carefully describes as a CD122-preferential IL-2 pathway agonist, could still fulfil the promise it has shown as a complement to PD-1 inhibitors.

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