Key second-quarter clinical readouts for pharma

This year has already seen a new Alzheimer’s approval and Lilly is hoping that upcoming pivotal data on its own candidate, donanemab, will prove convincing. In obesity, another important area for Lilly, Mounjaro data are due that will complete a rolling submission, while Novo’s successful obesity drug Wegovy has key cardiovascular outcomes data. 

Two major lung cancer readouts are also coming. The first concerns Merck's subcutaneous formulation of Keytruda, which is key to extending sales, and second will provide the first look at late-stage data on Daiichi and Astra’s Trop2 antibody-drug conjugate datopotamab deruxtecan. 

Second chance saloon 

The accelerated filing for Eli Lilly’s Alzheimer's disease candidate donanemab was knocked back in January 2023. Now data are due from the confirmatory phase 3 Trailblazer-Alz 2, and the combined dataset must prove competitive to Eisai and Biogen’s Leqembi, which has already gained an accelerated thumbs up. 

Lilly claimed that donanemab was turned down because the filing, which used phase 2 data, did not include enough patients with at least 12 months’ exposure to the MAb, a requirement for the safety database. Lilly stops dosing donanemab once patients’ plaque clears, and as Trailblazer-Alz 2 is much bigger than the phase 2 trial it should hopefully pass the safety requirement. 

The primary measure of Trailblazer-Alz 2 is change from baseline on the integrated Alzheimer’s disease rating scale, however focus will fall on a secondary endpoint, the clinical dementia rating scale-sum of boxes. This endpoint was the primary in Leqembi’s confirmatory Clarity-AD study where Leqembi-treated patients performed 27% better than those in the placebo group, at 18 months. 

Lilly has said that Trailblazer-Alz 2 data are due mid-year, so they could come around the same time as the FDA adcom to discuss full approval of Leqembi, the Pdufa for which is set for July. Leqembi’s accelerated approval was based on biomarkers and plaque clearance data.  

Safety will be another key comparison between donanemab and Leqembi. In Clarity-AD the rate of Aria-E, a brain inflammation side effect, was driven by carriers of the ApoE4 allele, with a rate of 15.8%; the overall rate was 12.6%. The rate of discontinuations due to side effects was just 6.9%, much lower than earlier data with donanemab, which in phase 2 showed comparable dropouts of nearly 30.5%. 

Novo vs Lilly 

With Eli Lilly’s Mounjaro breathing down its neck, Novo’s obesity therapy Wegovy needs an important cardiovascular benefit claim. The outcomes study which could allow this, Select, conducted in non-diabetic obesity, is expected to report by mid-year.  

Select is powered to detect a 17% benefit with Wegovy versus placebo on a composite endpoint evaluating cardiovascular death and non-fatal myocardial infarction or stroke. Sentiment around the potential strength of the final data received a blow last year after the trial continued following an interim look at efficacy.  

Lilly’s Mounjaro has produced impressive data in obesity patients already, with weight loss of just over 20% at 18 months in patients given the highest dose in the Surmount-1 study. Mounjaro looks competitive to Wegovy on a cross-trial basis, and with a cleaner tolerability profile.  

Weight loss data are now due from three further trials, Surmount-2 in type 2 diabetes patients, Surmount-3 in obese patients, and Surmount-4, testing maintenance of weight loss in obese patients. Alongside Surmount-1, data from Surmount-2 will complete the rolling obesity submission with Lilly gunning for an approval before the year is out. 

Mounjaro’s own outcomes study, Surpass-CVOT in patients with type 2 diabetes, does not complete until 2024. 

Key data in oncology  

A couple of oncology readouts are still in play, including Daiichi Sankyo and Astrazeneca’s datopotamab deruxtecan. Data is due from Tropion-Lung01 in treatment-refractory NSCLC. If the Trop2-targeted ADC can double median PFS compared with docetaxel, datopotamab will have a chance of replacing chemo in early NSCLC settings, Jefferies analysts believe.   

Lastly a pivotal trial of the subcutaneous formulation of Keytruda is set to report. The aim of the 3475-A86 study, in metastatic squamous or nonsquamous NSCLC, is to show that subcutaneous dosing is non-inferior to IV administration. The subcutaneous product will be key for Merck to prop up sales as the IV version loses exclusivity in 2028. 

The tables below contain a list of upcoming conferences and catalysts, with consensus forecasts from Evaluate Pharma.