Big pharma’s key second-quarter data
Roche awaits Tigit and Serd data, Lilly takes on obesity, and Glaxo and Pfizer race in RSV.
The second quarter promises several important oncology readouts for Roche, including data from the anti-Tigit tiragolumab, a key pipeline asset. And results from the company's oral Serd will show whether giredestrant can avoid the same fate as Sanofi’s recently failed amcenestrant.
Elsewhere, Lilly will hope that tirzepatide can take on Novo Nordisk in obesity with data from the project’s first pivotal study in this setting, while Glaxosmithkline and Pfizer head towards readouts in respiratory syncytial virus (RSV).
Key to the pipeline
Two studies will report with Roche’s anti-Tigit MAb tiragolumab: Skyscraper-01, which includes Tecentriq in first-line PD-L1-high NSCLC, and Skyscraper-02, with Tecentriq and chemotherapy in first-line small-cell lung cancer.
A positive outcome for Skyscraper-01 is expected given data from the earlier phase 2 Cityscape trial, which showed a 77% reduction in risk of death with the combo versus Tecentriq alone in PD-L1 ≥50% expressers.
Success in Skyscraper-02 could be harder to come by given the relative intractability of SCLC. However, Merck & Co recently started phase 3 in SCLC with its own Tigit MAb vibostolimab plus Keytruda and chemo, perhaps instilling some confidence in Roche’s strategy.
For Roche’s oral Serd giredestrant, phase 2 data from the Acelera study in ER-positive, Her2-negative breast cancer are expected. The results will come soon after the failure of Sanofi’s Serd amcenestrant, with questions over whether the trial design was to blame (No Ameera glory for Sanofi, March 14, 2022).
Like Sanofi’s Ameera-3 trial Acelera has not been enriched for patients with ESR1, a mutation said to be a key resistance mechanism to endocrine therapy. Data from Radius/Menarini’s rival project elacestrant clearly showed that it was the mutant group that drove the all-comers benefit. Unless Acelera’s endpoints are changed, another Serd disappointment could be looming.
Lilly’s GIP/GLP-1 agonist tirzepatide has shown impressive weight loss in type 2 diabetes, with FDA action due mid-year, and now data are expected from the project’s first pivotal obesity study.
Surmount-1 tests 5mg, 10mg or 15mg subcutaneous tirzepatide once a week versus placebo. The co-primary outcomes are the percent change from baseline in body weight, and the percentage of participants who achieve ≥5% body weight reduction at week 72.
Across tirzepatide’s Surpass-1 to 5 studies in type 2 diabetics, a 15mg dose demonstrated weight loss of between 11% at 40 weeks and 14% at 52 weeks. Lilly has said that it expects greater weight loss in non-type 2 diabetics than that seen in the Surpass studies.
Lilly is hoping to compete against Novo Nordisk’s obesity drug Wegovy, an injectable version of semaglutide that showed a non-placebo-adjusted weight loss of 15-16% at 68 weeks in non-diabetic patients in its Step programme.
Consensus forecasts from Evaluate Pharma shows Wegovy as the market leader in obesity by 2026, with sales of $3.8bn. A reliable consensus has yet to emerge for tirzepatide in obesity, though Cantor reckons this use could represent a "multi-billion dollar opportunity".
Crunch time in RSV
Two pivotal RSV vaccine candidates will yield data before mid-year, including GSK3844766A, Glaxo's most valuable pipeline project.
Berenberg analysts believe that Glaxo's phase 3 study Aresvi 006, in elderly people, will need to show efficacy of 70% or greater to be classed as a success. At around the same time Pfizer’s RSVpreF will also yield data from a maternal protection study and an adult trial called Renoir. Development of Glaxo's own maternal candidate has been paused on safety concerns.
Competition continues to hot up in RSV, with data from J&J's Ad26.RSV.preF in adults expected in the second half of the year.
The tables below contain a list of upcoming conferences and catalysts, with consensus forecasts from Evaluate Pharma.
|Esmo ELCC||Lung cancer||March 30-April 2|
|DDW||Digestive diseases||May 21-24|
|Clinical catalysts in Q2 2022 (excludes Covid-19 data)|
|Product||Company||Therapy area||Q2 clinical catalyst||2026e indication sales ($m)||Note/Vantage coverage|
|Imfinzi||Astrazeneca||1L NSCLC||Ph3 Pearl (Asia) H1||3,301*||Primary endpoint is OS in PD-L1 ≥25% (Tori’s lung cancer hit raises a key question)|
|Imfinzi + platinum-CRT||Astrazeneca||Stage III NSCLC||Ph3 Pacific-2||Fourth-quarter events to watch for big pharma|
|Merck & Co||Locally advanced head and neck cancer||Ph3 adj Keynote-412||1,434*||Keytruda has 1L label (monoRx in PD-L1≥1%, or chemo combo in all-comers), but failed Keynote-040, potentially confirmatory 2L study (Immuno-oncology spotlight falls on cervical cancer)|
|Roche||1L NSCLC PD-L1+ve, 1L SCLC||Ph3 Skyscraper-01 (NSCLC), Skyscraper-02 (SCLC)||1,240 (SBI not split out)||See text, Skyscraper-04 (2/3L PD-L1+ve cervical cancer) and Skyscaper-08 (1L oesophageal) expected H2|
|Prevnar 20||Pfizer||Pneumonia (vaccine)||Pivotal in infants, Japan data H1 (three global studies H2)||1,232 (already approved in adults)||Accelerated approval in adults already, Merck's 15 valent version, Vaxneuvance, has a Pdufa in April for 6 weeks to 17 years old|
|Lebrikizumab||Lilly/Roche/ Almirall||Atopic dermatitis||Ph3 maintenance data (Advocate 1 & 2) & ph3 steroid combo data (Adhere) due H1||1,024||AAD 2022 – Lilly gears up to take on Dupixent|
|GSK3844766A||Glaxosmithkline||RSV (in adults ≥60) (vaccine)||Ph3 Aresvi 006 H1||765||See text|
|Farxiga||Astrazeneca||Heart failure with preserved ejection fraction (HFpEF)||Ph3 Deliver H1||559 (on the market for HFrEF)||Boehringer's Jardiance was approved in Feb in HFpEF|
|RSVpreF (PF-06928316)||Pfizer||RSV (maternal protection & in adults ≥60) (vaccine)||Ph3 maternal protection trial, Ph3 Renoir in adults ≥60||444||See text (RSVVW 2021 – Pfizer gets maternal)|
|Giredestrant||Roche||2/3L, pre/peri/ postmenopausal ER+/Her2- breast cancer||Ph2 Acelera||400||See text|
|Novo Nordisk||Type 2 diabetes||Ph3a Onwards 2 (on basal, 26wk, vs degludec), 3 (treatment naive, 26wk, vs degludec), 4 (on basal and bolus, 26wk, vs glargine + aspart)||185||Once weekly basal insulin (Lilly’s Protomer deal shows innovation in diabetes is not dead)|
|ABBV-3067 +/- ABBV-2222
|Abbvie||Cystic fibrosis||Ph2 Potentiator + corrector
Ph2 two correctors + potentiator 2022
|21||Via Galapagos (JP Morgan 2022 – Abbvie looks to crack the cystic fibrosis code)|
|PF-06650833 +/- ritlecitinib
|Pfizer||RA||Ph2||9||Irak-4 inhibitor and Jak3/Tec Inhibitor|
|Tirzepatide||Lilly||Obesity||Ph3 Surmount-1 mid year||-||See text|
|Talzenna + Xtandi
|Pfizer||1L all comers, metastatic CRPC||Pivotal Talapro-2||-||Parp inhibitor (Asco-GU – prostate cancer Parps move to the front line)|
|*Already on the market in different settings. Source: clinicaltrials.gov, Evaluate Pharma & company releases.|