Approaching datasets for big pharma

J&J moves FcRn towards a big new therapy area, while Bristol, Merck, Astrazeneca and Daiichi Sankyo await important oncology catalysts. 

Diving into upcoming clinical readouts for big pharma sees J&J awaiting news on its attempt to move its anti-FcRn nipocalimab into rheumatoid arthritis. A win here would open up a potentially big use for this mechanism.

In oncology Bristol Myers Squibb is moving Lag3 into lung cancer with Opdualag, and Astrazeneca’s Akt inhibitor capivasertib will yield data in triple-negative breast cancer. Meanwhile data are still awaited from subcutaneous Keytruda, Enhertu in ultra-low Her2, and datopotamab in lung cancer. 

Move into arthritis 

The anti-FcRn space is crowded with several readouts to watch over the next 12 months. While myasthenia gravis looks to be the lead indication for the space, J&J is expecting proof of concept data in rheumatoid arthritis, a bigger commercial opportunity. 

J&J’s phase 2 study tests intravenous nipocalimab given every two weeks versus placebo, with both arms also on standard of care. The trial is enriched for patients with certain autoantibodies associated with RA, and enrolled those who are TNF-refractory. 

The trial’s primary endpoint is change from baseline in DAS28-CRP, a measure of disease activity, at week 12. Abbvie’s Jak1 inhibitor Rinvoq sets the efficacy bar in rheumatoid arthritis with a delta of around -1.3 between placebo and treatment. However, Rinvoq also comes with a boxed warning so a safety win for nipocalimab would be a bonus. 

Key oncology datasets 

There are several lung and breast cancer readouts coming up for big pharma. In lung cancer, the first Lag3 data from Bristol Myers Squibb are due. The aim is to move Opdualag, a Lag3 and PD-1 combination, beyond its approved use in melanoma. 

An interim look at phase 2 is expected this year. The study is enrolling 420 patients with first-line metastatic NSCLC, and Opdualag plus platinum doublet chemotherapy is pitted against Opdivo plus chemotherapy. The primary measures are adverse events and overall response rate. 

Regeneron’s rival Lag3 asset, fianlimab, in combination with Libtayo, is in two phase 2/3 studies in advanced NSCLC. The trials, one with chemotherapy, and one without, have only recently started recruiting, however. 

In breast cancer, meanwhile, Astrazeneca is set to report data with its Akt inhibitor capivasertib in first-line triple-negative disease. The Capitello-290 study combines capivasertib with paclitaxel versus paclitaxel alone, with overall survival as the primary measure. 

Capivasertib plus Faslodex has already scored in ER-positive Her2-negative breast cancer, where it has a fourth-quarter Pdufa date. Roche has a competing Akt inhibitor, ipatasertib, which has suffered numerous clinical setbacks. 

Worth waiting for 

One oncology catalyst Vantage has dived into before is Merck & Co’s subcutaneous Keytruda formulation, in a lung cancer study called 3475-A86. This could be key to maintaining sales when the intravenous version loses exclusivity in 2028, though recently Merck has been putting the focus on a separate trial, using six-week dosing

Investors are also still awaiting data from Daiichi Sankyo/Astrazeneca’s Destiny-Breast06 study, which is intended to move Enhertu into ultra-low Her2 patients. The partners are also due to report key data with another antibody drug conjugate, datopotamab deruxtecan, from Tropion-Lung01 in treatment-refractory NSCLC and Tropion-Breast01 in ER-positive Her2-negative breast cancer.  

There have been hints of efficacy with datopotamab in breast and lung settings, including encouraging response rates in an early first-line lung study, reported at Asco. 

The table below contains a list of upcoming catalysts, with consensus forecasts from Evaluate Pharma. Readouts specifically in the fourth quarter are excluded. 

Big pharma clinical catalysts in Q3/H2 2023
Product Company  Therapy area Q3/H2 clinical catalyst 2028e indication sales ($m) Note/ Vantage coverage
Tagrisso  Astrazeneca EGFRm NSCLC (maintenance) Ph3 Laura (unresectable) H2 8,347* Lazertinib and Tagrisso go head to head (Flaura2 in front-line patients toplined positive)
Enhertu Daiichi Sankyo/ Astrazeneca HR+/Her2 low 2L+ metastatic breast cancer (chemo naive) Ph3 Destiny-Breast06 H2, includes a Her2 ultra low cohort 6,095* See text
Datopotamab deruxtecan (DS-1062) Daiichi Sankyo/ Astrazeneca 2/3L NSCLC, 2/3L HR+/Her2 low or negative breast cancer Ph3 Tropion-Lung01 vs docetaxel (includes patients failed on immunotherapy), ph3 Tropion-Breast01 Q3 2,590 See text
SubQ Keytruda
(MK-3475 SC)
Merck & Co 1L NSCLC Ph3, primary completion April 2023 2,590 See text
Rybrevant J&J 1L NSCLC Ph3 Papillon (+ chemo) guided to 2023 1,151* Possibly confirmatory study (Lazertinib and Tagrisso go head to head)
Nipocalimab J&J Rheumatoid arthritis Ph2 CR109058 guided to 2023 949** See text
Tiragolumab + Tecentriq Roche PD-L1 high 1L NSCLC Ph3 Skyscraper-01 final OS Q3 870 Missed at interim analysis on PFS, there was a numerical trend favouring an OS benefit (Looking beyond Roche’s Tigit bombshell)
V116 Merck & Co Pneumococcal disease prevention in adults Ph3 Stride 3 (vs Prevnar 20), 4 (vs Pneumovax 23) and 6 (revaccination, vs Vaxneuvance, Pneumovax 23) Q3 604 21-valent offering, three further studies ongoing
Navitoclax Abbvie 1L myelofibrosis Ph3 Transform-1, + Jakafi vs Jakafi H2 573 Asco 2022 – Abbvie goes back to basics with navitoclax
Capivasertib + paclitaxel Astrazeneca 1L triple negative breast cancer Ph3 Capitello-290 H2 507 See text
Iptacopan Novartis IgAN Ph3 Applause-IgAN (proteinuria data for accelerated filing) Q3 451 Planning to buy Chinook (data Q4) (Calliditas sets the bar for its kidney disease rivals)
Imfinzi Astrazeneca Muscle-invasive bladder cancer Ph3 Niagara H2 - Plus chemo
Opdualag Bristol Myers Squibb 1L NSCLC Ph2 CA224-104 guided to 2023 - See text
Subcutaneous Ocrevus Roche Multiple sclerosis (RMS and PPMS) Ph3 Ocarina II vs intravenous Ocrevus H2 - Push to an at home setting, Novartis already has a subQ version of Kesimpta
*On the market already in different treatment line/indication setting; **forecasts not split out. Sources: Evaluate Pharma, analyst notes &

Evaluate Vantage has published two further catalyst stories, one for big biotech, and the other covering smaller companies.


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