Big pharma’s new year catalysts
In the opening months of 2023 Novo Nordisk needs to defend its position, while Daiichi and Astrazeneca await ADC data.
If 2022 was about progress in Alzheimer’s, the new year looks to start with a battle in metabolic disorders, namely type 2 diabetes and obesity. Novo Nordisk is hoping to maximise efficacy of the oral formulation of its GLP-1 agonist semaglutide, by ramping up the dose, to help fend off threats from Lilly’s Mounjaro.
Elsewhere, Astrazeneca and its partner Daiichi will see data from two antibody-drug conjugates. Enhertu will try its chances in ultra-low Her2 breast cancer while datopotamab deruxtecan is in immunotherapy-failed lung cancer patients. Pfizer and Roche, meanwhile, are gunning for haemophilia B with the gene therapy fidanacogene elaparvovec, although CSL and Uniqure have got there first.
Lilly’s Mounjaro might be the new kid on the metabolic block but Novo is not standing still. In diabetes, oral semaglutide is branded Rybelsus and is approved at a 14mg dose. A study called Pioneer Plus is testing 25mg and 50mg, compared with 14mg, over 52 weeks. Rybelsus achieved a placebo-adjusted blood sugar reduction of 1.1 percentage points in its 26-week Pioneer 1 study.
Perhaps more important are obesity data, from a study called Oasis 1, which tests 50mg oral semaglutide versus 14mg.
Oasis 1 is a 660-participant, 68-week study. The 50mg dose is achieved by dose escalating across 16 weeks and the primary endpoints are the relative change in body weight, and an achievement of body weight reduction greater than or equal to 5%.
The aim is to achieve Wegovy-type weight loss; Wegovy is the brand name of injected semaglutide approved in obesity. The drug has shown a placebo-adjusted -12.4 percentage point change in body weight at week 68. The most common adverse events were gastrointestinal, which will be watched closely in Oasis 1.
Lilly’s Mounjaro is already approved in type 2 diabetes and a filing in obesity is expected before the end of 2023. At the same time, oral projects are in development from Lilly, Pfizer and Amgen, so Novo needs to keep up the pace.
More ADCs on their way
Daiichi Sankyo and Astrazeneca’s antibody-drug conjugate heavy weight Enhertu already has three breast cancer settings on its label, including Her2 low, and the developers are striving to add more. Next up are data in Her2-low patients who are also hormone receptor (ER) positive; the study also includes a Her2 ultra-low cohort, and any signal here could open up an even wider pool of patients.
The Destiny-Breast06 study pits Enhertu against chemotherapy in ER-positive patients whose disease has progressed on endocrine therapy in the metastatic setting. The primary measure is PFS.
Her2-low patients are defined as having an immunohistochemistry (IHC) score of 1+, or IHC2+ with a negative in-situ hybridisation score (ISH-). Those with an expression of Her2 greater than zero but less than 1 are known as ultra-low.
Another antibody-drug conjugate from Daiichi and Astra has key data due in lung cancer. Datopotamab deruxtecan is a Trop 2-directed conjugate that uses the same toxic payload as Enhertu.
The pivotal Tropion-Lung01 study is in a broad second-line NSCLC setting and includes patients who have previously been treated with a PD-(L)1 MAb. Datopotamab is up against docetaxel and the primary endpoints are PFS and overall survival.
While Keytruda has reshaped the first-line lung setting, the I-O failure space remains wide open.
Next in line
Pivotal data are expected soon from Pfizer and Roche’s haemophilia B gene therapy, fidanacogene elaparvovec. The partners are completing the Benegene-2 trial in 45 male patients. The primary measure is the annualised bleeding rate from week 12 to month 15.
Uniqure and CSL recently gained FDA approval for their gene therapy, Hemgenix, which has set a high efficacy precedent. Its approval was based on the Hope-B study where Hemgenix showed an estimated mean annualised bleeding rate of 1.9 bleeds/year during months 7 to 18, which was assessed as non-inferior to the rate in the lead-in period.
The project also looks durable, with mean factor IX activity at 24 months similar to 3-month values.
The table below contains a list of upcoming catalysts with consensus forecasts from Evaluate Pharma.
|Big pharma clinical catalysts in Q1 2023|
|Project||Company||Therapy area||Q1 clinical catalyst||2028e indication sales ($m)||Note/ Vantage coverage|
|Novo Nordisk||Type 2 diabetes||Ph3 Pioneer Plus H1 (25mg, 50mg vs 14mg)||5,964*||See text|
|Enhertu||Daiichi Sankyo/ Astrazeneca||Her2-low 2L+ metastatic breast cancer||Ph3 Destiny-Breast06 H1||5,493*||See text|
|Datopotamab deruxtecan (DS-1062)||Daiichi Sankyo/ Astrazeneca||2/3L NSCLC||Ph3 Tropion-Lung01 vs docetaxel H1||2,170||See text|
|Dupixent||Sanofi||Chronic inducible cold urticaria||Pivotal Ph3 Liberty-CINDU CUrIADS H1||1,409||Cupid Study B failed in chronic spontaneous urticaria patients refractory to Xolair|
|Pluvicto (177Lu-PSMA-617)||Novartis||mCRPC chemo-naive||Ph3 PSMAfore details possibly at Asco GU in Feb (according to SVB analysts)||1,050||Toplined positive, stat sig improvement in radiographic PFS in PSMA-positive mCRPC|
|Tecentriq||Roche||Adjuvant SCCHN||Ph3 Imvoke010 guided to 2023||777||Opdivo has a 2L approval, while Keytruda has a 1L label, either as monotherapy in PD-L1 ≥1% expressers, or as a chemo combo in all-comers|
|Tiragolumab + Tecentriq||Roche||PD-L1 high 1L NSCLC||Ph3 Skyscraper-01 OS data, interim Q1, final H2||770||In terms of PFS tiragolumab + Tecentriq failed to beat Tecentriq, although there was a numerical benefit|
|Fidanacogene elaparvovec||Pfizer/Roche||Haemophilia B||Ph3 pivotal Benegene-2||449||Gene therapy, Uniqure/CSL's Hemgenix received FDA approval in November|
|Iptacopan||Novartis||IgAN, C3 glomerulopathy||Ph3 Applause-IgAN, Ph3 Appear-C3G, guided to 2023||388||IgAN: Primary endpoint for US accelerated submission, 9 months UPCR, competitor Travere's Pdufa for sparsentan due Feb|
|Navitoclax||Abbvie||1L myelofibrosis||Ph3 Transform-1 (+ Jakafi vs Jakafi alone)||346||Asco 2022 – Abbvie goes back to basics with navitoclax|
|Roche||PNH||Ph3 Commodore-1 (complement experienced), Commodore-2 (complement naive)||297||Non-inferiority of SC crovalimab versus Astra’s IV Soliris|
|Merck & Co||1L NSCLC||Ph3, PC February||-**||Chemo combo of Keytruda SC vs IV|
|BMS-986278||Bristol Myers Squibb||IPF||Ph2 guided to 2023||-||Small molecule LPA1 antagonist, Abbvie bought DJS Antibodies for its LPA1 antibody (Abbvie grabs an antibody against an elusive target)|
|Dupixent||Sanofi||COPD||Pivotal Ph3 Boreas H1||-||Company expects to submit on a rolling basis, a second Ph3, Notus, expected early 2024|
|Imfinzi||Astrazeneca||1L ovarian cancer & Imfinzi/Avastin/ Lynparza maintenance||Ph3 Duo-O Imfinzi + Avastin + chemo (+ Lynparza) vs Avastin + chemo H1||-||PFS primary|
|Novo Nordisk||Obesity||Ph3a Oasis 1 H1 (50mg once daily)||-||See text|
|Nipocalimab||J&J||RA||Ph2 H1||-||IV anti-FcRN project, primary completion in November for myasthenia gravis|
*On the market already as different dose/treatment line, **Subcutaneous forecasts not split out. PC: primary completion, SC: subcutaneous, IV: intravenous. Source: Evaluate Pharma, clinicaltrials.gov.