Oncology the focus for big pharma catalysts
The fourth quarter will see key immunotherapy data from Astrazeneca and Merck, while full details on Glaxo's anaemia pill, daprodustat, are expected.
The final three months of 2021 will see numerous cancer updates from the big pharma players, including Astrazeneca in first-line liver cancer and Merck in adjuvant lung, as well as Gilead and Sanofi in breast cancer.
Glaxosmithkline, meanwhile, will reveal full details on its anaemia pill daprodustat. Investors will want to know whether data can justify or dispel cardiovascular safety concerns that have dogged HIF-PH inhibitors, the class of drug to which daprodustat belongs.
Results are expected at a medical meeting, potentially at the American Society of Nephrology's Kidney Week in early November. Glaxo's daprodustat is intended to treat anaemia due to chronic kidney disease; all the company has said so far is that all five studies in the 8,000-patient Ascend pivotal programme met their primary endpoint, with daprodustat showing non-inferiority to an erythropoietin-stimulating agent on the risk of major adverse cardiovascular events.
Concern about cardiac safety was the main issue that scuppered Fibrogen and Astrazeneca's rival project roxadustat in the US: the FDA issued a complete response letter in August and demanded another trial. In Europe, however, where Astellas owns marketing rights, the EMA granted approval.
Akebia’s vadadustat too has had safety issues; that project's Pdufa date is next March and a European filing is expected this year.
Immunotherapy in liver cancer
Moving on to oncology, Astrazeneca’s Imfinzi is gunning for a place in first-line liver cancer with phase 3 data expected soon. Roche’s Tecentriq has set a high bar to beat, however.
Imbrave-150, which led to the approval of Tecentriq plus Avastin, reduced the risk of death by 42% (p=0.0006) and cut the risk of disease worsening or death by 41% (p<0.0001) versus Nexavar.
Astra’s Himalaya trial, due to report in the fourth quarter, tests Imfinzi as monotherapy and in combination with the anti-CTLA-4 agent tremelimumab, against Nexavar. The primary outcome is overall survival.
The combination of Imfinzi plus treme has in the past failed in various cancer settings, although treme has seen a revival of late in lung cancer. The Imfinzi monotherapy arm could beat Nexavar but standing up to Tecentriq’s combination results might be difficult.
A big readout on the horizon for Merck & Co's Keytruda is the Keynote-091 study in adjuvant NSCLC. The trial tests the drug in stage IB-IIIA patients regardless of PD-L1 expression, with a primary endpoint of disease-free survival.
Roche’s Tecentriq has a head start here with a Pdufa set for December 1, though data from Impower-010 suggest that Tecentriq’s use will likely to be limited to PD-L1-expressing stage II-IIIA patients.
Adjuvant/neoadjuvant settings are becoming more important for immunotherapies. Keytruda already has melanoma and triple-negative breast cancer on its label, and two US regulatory decisions, in renal cell cancer and high-risk stage II melanoma, are due in December.
The following tables contain details of upcoming conferences and a fuller list of catalysts, with consensus forecasts from Evaluate Pharma.
|Meeting||Area of focus||Date|
|Triple meeting||Oncology||Oct 7-10|
|Kidney Week||Nephrology||Nov 4-7|
|CTAD 2021||Alzheimer's||Nov 9-12|
|SITC 2021||Immunotherapy||Nov 10-14|
|AHA 2021||Cardiovascular||Nov 13-15|
|SABCS||Breast cancer||Dec 7-10|
|Ash 2021||Haematology||Dec 11-14|
|Q4 clinical catalysts (excludes Covid-19 data)|
|Product||Company||Therapy area||Q4 clinical catalyst||2026e indication sales ($m)||Note/Vantage coverage|
|Keytruda||Merck & Co||Adjuvant (stage Ib-IIIa) NSCLC||Ph3 Keynote-091/Pearls||4,484*||See text|
|Vraylar||Abbvie||Major depressive disorder||Ph3 adjunctive treatment, NCT03738215, NCT03739203||1,345 (incl bipolar depression)||Already approved in schizophrenia, manic episodes associated with bipolar disorder and bipolar depression|
|Trodelvy||Gilead||3L Her2-/HR+ breast cancer||Ph3 Tropics-2||2,452*||The heat is on Gilead as Tropics readout nears|
|Sarclisa (+ Velcade + Revlimid + dex)||Sanofi||Transplant ineligible multiple myeloma||Pivotal Imroz study||931*||Darzalex dominates the space (Empliciti’s front-line flop underlines Darzalex’s dominance)|
|Ligelizumab||Novartis||Chronic spontaneous urticaria||Ph3 Q4/Q1 2022 Pearl 1, 2 (versus Xolair, inadequately controlled by antihistamines)||652||Anti-IgE MAb, Xolair, also an anti-IgE MAb was approved in 2014, Dupixent is also being tested in the condition|
|Mirikizumab||Eli Lilly||Ulcerative colitis||Ph3 maintenance data Lucent 2||571||Comparator Stelara had 60%+ success in maintaining remission|
|Jemperli (dostarlimab)||GSK||1L endometrial cancer||Ph3 Ruby, + carboplatin-paclitaxel||569*||PD-1 antibody, label currently has mismatch repair deficient recurrent or advanced endometrial cancer|
|Amcenestrant||Sanofi||3L ER+/Her2- breast cancer||P2 Ameera-3||485||Oral Serd, data delayed from Q2, data with Radius' elacestrant also expected Q4 (Validation for a drug class, and for Sanofi)|
|GSK||CKD anaemia||Ph3 five studies in Ascend, full data at meeting (poss Kidney Week Nov 4-7)||444||See text|
|Imfinzi +/- tremelimumab||Astrazeneca||1L liver cancer||Ph3 Himalaya (versus Nexavar)||144||See text|
|Etrolizumab||Roche||Crohn's||Ph3 Bergamot||87||Mixed data in ulcerative colitis (Etrolizumab’s novelty wears off)|
|Zagotenemab||Eli Lilly||Alzheimer's disease||Ph2||61||Anti-tau MAb, many setbacks in the space (AC Immune claims a tau win in Alzheimer’s), also watch for donanemab filing by YE|
|NSCLC||Ph2 Amber||27||Tim-3, proof of concept data|
|Oleclumab +/- Imfinzi + chemo||Astrazeneca||1L/2L pancreatic cancer||Ph1b/2||2||Anti-CD73 mAb, primary endpoint is safety and anti tumour activity|
|Ilaris (+/- Keytruda + chemo)||Novartis||1L NSCLC||Final Canopy-1 readout||-||Canopy-1 passed its interim analysis in Oct 20, falling short of efficacy criteria for early stopping, Canopy-2 (2/3L, cana + docetaxel) failed in March (Cana can’t – can Cantargia?)|
|ARV-471||Pfizer/Arvinas||3L ER+/Her2- breast cancer||Ph1 dose escalation data anticipated at SABCS (Dec 7-10)||-||Another oral Serd, note Sanofi and Radius data due Q4 (The search for a better Faslodex continues)|
|*Already approved in indication at different treatment line. Source: analyst notes, clinicaltrials.gov, Evaluate Pharma.|