Heading towards the end of 2020, a year dominated by Covid-19, Evaluate Vantage has delved into data releases expected from big pharma in the fourth quarter. Excluding readouts expected from coronavirus therapies and vaccines, oncology looks to dominate with Astrazeneca, Gilead, Takeda and Glaxosmithkline all due to unveil important updates.
Elsewhere Alzheimer’s comes into play for Roche, while both Bristol Myers Squibb and Pfizer have Tyk2 inhibitors in development for psoriasis, on which the first data are pending. The first look at Lilly's GIP/GLP-1 agonist tirzepatide should also emerge.
Astrazeneca’s immunotherapy Imfinzi is well established in stage III NSCLC, but only after chemoradiotherapy (CRT). Data are expected from Pacific-2 in an earlier setting − Imfinzi will be given with CRT versus CRT alone. The primary endpoint is PFS.
The hope is that Pacific-2 can help defend against competitors aiming to beat the efficacy achievable with Imfinzi after CRT, as well as those targeting the earlier population. Data at Asco from Merck & Co’s Keytruda showed a 56.6% remission rate, and six-month overall survival of 94.8%, in the Keynote-799 study where Keytruda was given with CRT, though this was an uncontrolled study.
Data are also expected from Imfinzi in first-line liver cancer. The Himalaya trial tests Imfinzi as a monotherapy, or in two combinations with the anti-CTLA-4 agent tremelimumab, against Nexavar; the primary outcome is overall survival.
The readout will draw comparisons with Imbrave-150, which led to the approval of Roche's Tecentriq plus Avastin as a first-line treatment, which reduced risk of death by 42% (p=0.0006) and cut the risk of disease worsening or death by 41% (p<0.0001) versus Nexavar.
Jefferies analysts note that Imfinzi monotherapy could beat Nexavar, but it will be difficult to beat Tecentriq’s combination results. Prior failures with Imfinzi plus tremelimumab in various cancer settings mean that expectations are low for the Astra combination.
Elsewhere in cancer
Takeda’s pevonedistat, a first-in-class NEDD8-activating enzyme (NAE) inhibitor, should yield phase III data soon. The aim is to improve on the chemotherapy drug Vidaza, with pevonedistat given in combination versus Vidaza alone.
The Panther study is in 454 patients with high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia, or low-blast AML. The primary endpoint is event-free survival, with OS a secondary measure.
Phase II data were reported at this year’s Asco, and showed benefit particularly in 67 patients in the high-risk MDS subgroup in terms of event-free survival, the primary endpoint. The results were 20.2 months versus 14.8 months, but in the intent-to-treat population the difference in event-free survival was not statistically significant.
Gilead’s anti-CD47 MAb magrolimab has shown impressive response data in MDS in a phase Ib study. MDS is the project's most advanced indication, with the phase III Enhance trial under way, but DLBCL data are expected in the fourth quarter. The results, likely at the Ash conference in December, will come from a phase I/II study testing magrolimab in combination with Rituxan.
Magrolimab was gained through Gilead’s $4.9bn acquisition of Forty Seven; two months after that deal Gilead bought a stake in Arcus Biosciences to gain access to the biotech's cancer pipeline, data from which are expected next quarter.
Arc-7 is a phase II study in PD-L1-positive NSCLC patients. The trial has three arms: monotherapy with the checkpoint inhibitor zimberelimab, zimberelimab plus the anti-Tigit MAb AB154, and lastly both plus AB928, an adenosine A2B receptor antagonist. Arcus intends to disclose data for half of the patients, approximately 25 in each arm.
The Tigit mechanism has generated interest from Merck and Roche, with the latter having the most advanced candidate, tiragolumab. As a benchmark for Arcus’s upcoming data Roche’s Cityscape trial showed the highest overall remission rate in PD-L1 high (≥50%) patients in combination with Tecentriq − 55.2% versus Tecentriq’s 17.2%. There was no clinical benefit in PD-L1-low patients.
Through the Arcus deal Gilead gained immediate rights to zimberelimab, but should the Arc-7 data prove competitive Mizuho analysts see Gilead exercising opt-in rights for AB154, with a broader development strategy following shortly.
Oncology aside there are several readouts due from Roche's beta-amyloid MAbs in Alzheimer’s; last week the company's anti-tau MAb semorinemab failed in phase II. Elsewhere two Tyk2 inhibitors will generate data, with Bristol Myers Squibb leading the pack here and Pfizer following in psoriasis.
Check out the table below for a full list of upcoming catalysts with consensus forecasts from EvaluatePharma.
|Selected Q4 clinical catalysts (excludes Covid-19 data)|
|Product||Company||Therapy area||Q4 catalyst||2026e indication sales ($m)||Note/Vantage coverage|
|Imfinzi + platinum-based CRT||Astrazeneca||Stage III NSCLC||Pacific-2||3,296||See text|
|Abbvie||Crohn's disease and psoriatic arthritis||Ph3: crohn's disease induction (Motivate), psoriatic arthritis (Keepsake2)||2,440||Crohn's disease forecasts make up over a third of Skyrizi's 2026 sales|
|Tirzepatide||Lilly||Type 2 diabetes||Surpass-1 (first of five trials from Surpass program)||2,202||Tirzepatide’s time to shine for Lilly|
|BMS-986165||Bristol Myers Squibb||Psoriasis||Ph3, Poetyk-PSO-1, vs placebo & vs Otezla||1,810||Bristol hopes to Tyk the psoriasis box|
|Blenrep (+ two SOC regimens)||Glaxosmithkline||2L multiple myeloma||Ph2 Dreamm-6||1,213||Approved in later setting with black box warning and REMS programme|
|Tezepelumab||Astrazeneca/ Amgen||Severe non-eosinophilic asthma||Ph3 Navigator||1,021||Previous failure in atopic dermatitis, Amgen and Astra hope to carve out a place in asthma|
(TAK-924) +/- azacitidine
|Takeda||Higher-risk myelodysplastic syndromes||Ph3 Panther||634||See text|
|Faricimab||Roche||Diabetic macular edema||Ph3 Yosemite, Rhine, vs Eylea||610||Showed improvement over Lucentis in Ph2, tougher test against Eylea|
|AB154 + zimberelimab +/- AB928||Gilead/Arcus||1L NSCLC||Ph2 Arc-7||460||See text|
|Omecamtiv mecarbil + SOC||Amgen/ Cytokinetics||Chronic heart failure with reduced ejection fraction||
Ph3 vs SOC; data at AHA (Nov 14-16)
|422||>8,000-patient trial, primary endpoint time to CV death or first heart failure event|
|Imfinzi +/- tremelimumab||Astrazeneca||1L liver cancer||Himalaya||129||See text|
|Magrolimab + Rituxan||Gilead||DLBCL||Ph1/2 data likely at Ash (Dec 5-8)||72||See text|
|Gantenerumab||Roche||Alzheimer's disease (prodromal)||Ph3 Scarlet Road||72||Alzheimer’s catalysts round off a year dominated by Biogen|
|Gantenerumab (brain shuttle) / RG6102||Roche||Healthy volunteers||Ph1||-|
|PF-06826647||Pfizer||Psoriasis||Ph2 proof-of-concept||-||Tyk2 inhibitor, ~2yrs behind BMS-986165|
|Roche||Myelofibrosis||Ph2||-||1st-in-class rhPTX-2, has BTD in for IPF with ph3 to start Q4|
|Sources: Evaluatepharma, clinicaltrials.gov, company releases & analyst notes.|