Key second-quarter clinical readouts for pharma

Lilly’s Alzheimer's and obesity results, outcomes for Novo Nordisk and oncology data for Merck & Co and Astrazeneca.

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. 

Upcoming conferences 
14-19 April 
Digestive diseases 
6-9 May 
2-6 June 
8-15 June 


Big pharma clinical catalysts in Q2 2023
Product Company  Therapy area Q2 clinical catalyst 2028e indication sales ($m) Note/Vantage coverage
Tagrisso  Astrazeneca 1L EGFRm NSCLC Ph3 Flaura-2 (+/- chemo) 8,499* See Lazertinib and Tagrisso go head to head
Wegovy Novo Nordisk Obesity Ph3 Select cardiovascular outcomes study, to complete mid-year 8,466 See text
Rybelsus (oral
Novo Nordisk Obesity Ph3a Oasis 1 (obesity) (50mg once daily) 5,685* See Big pharma’s new year catalysts
Mounjaro (tirzepatide) Eli Lilly Obesity Ph3 Surmount-2 (type 2 diabetes), Surmount-3 and Surmount-4 (both in overweight patients, the latter testing maintenance of weight loss) 5,361 See text
SubQ Keytruda
(MK-3475 SC)
Merck & Co 1L NSCLC Ph3 3475-A86, PC February 2,970 See text and Immuno-oncology goes subcutaneous
Alecensa Roche/
Adjuvant ALK+ NSCLC Ph3 Alina guided to 2023 2,599* Primary is disease free survival
Donanemab Eli Lilly Alzheimer's disease Ph3 Trailblazer-Alz2 mid year 2,181 See text
Datopotamab deruxtecan (DS-1062) Daiichi Sankyo/ Astrazeneca 2/3L NSCLC Ph3 Tropion-Lung01 vs docetaxel (includes patients who have failed on immunotherapy) 2,029 See text and The first big test for the son of Enhertu
Tecentriq Roche Adjuvant SCCHN, adjuvant TNBC Ph3 Imvoke-010 monotherapy (SCCHN), Impassion-030 (TNBC)  + chemo vs chemo 1,209 In SCCHN Opdivo has 2L approval & Keytruda has 1L label; Tecentriq's accelerated approval in 1L TNBC was withdrawn in 2021
Imfinzi Astrazeneca Adjuvant hepatocellular carcinoma Ph3 Emerald-2 (+/- Avastin) 350* Approved in met setting, Roche's Imbrave-050 (Tecentriq + Avastin) was said to have succeeded (Tecentriq surprises in adjuvant liver cancer)
Johnson & Johnson RSV (adults ≥60) Ph3 Evergreen 347 Competitive space, GSK and Pfizer both filed (GSK gets the vaccine edge on Pfizer)
Pfizer Haemophilia A or B patients with or without inhibitors Ph3  213 Anti-TFPI; Novo's concizumab is similarly acting and has a Pdufa H1 in inhibitor +ve
Lazertinib +/- Rybrevant J&J 1L EGFR mutant advanced lung cancer Ph3 Mariposa vs Tagrisso potential interim 203 See Lazertinib and Tagrisso go head to head
Keytruda +/- mRNA-4157 Merck/Moderna Adjuvant melanoma Detailed data from Ph2b Keynote-942 at AACR 16 April 58 Neoantigen cancer immunotherapy (lipid-encapsulated mRNA) reported positive topline, see AACR 2023 – Moderna's immunotherapeutic splash
Keytruda +/- autogene cevumeran Roche/Biontech Previously untreated advanced melanoma Ph2 Imcode001 54 Lipid-encapsulated mRNA (AACR 2020 – Biontech and Roche try to resuscitate cancer vaccines)
Sotyktu Bristol Myers Squibb Mod to severe Crohn's disease Ph2 Lattice-CD H1 - Disappointing data in ulcerative colitis could readthrough to Crohn's  (Lattice miss is grating for Bristol Myers)
Tozorakimab (MEDI3506) Astrazeneca Uncontrolled moderate to
severe asthma
Ph2 Frontier-3 - Anti-IL-33 MAb (Astrazeneca gets personal)
*Already approved in different treatment line. SCCHN: squamous cell carcinoma of the head and neck, TNBC: triple negative breast cancer. Sources: Evaluate Pharma, analyst notes,

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