More details needed on Sanofi’s atopic dermatitis win

 Sanofi has been on a shopping spree in the past couple of years, but not all its purchases have worked out. The latest deal to come under the spotlight is the $1.1bn acquisition of Kymab and its anti-Ox40-ligand antibody amlitelimab, with Sanofi today toplining a positive result from the phase 2b Stream-AD trial in atopic dermatitis.

The group is saving the data for a future medical meeting, but earlier results suggest that amlitelimab might struggle to match approved atopic dermatitis therapies including Sanofi and Regeneron’s own Dupixent. Still, the newer project could have a convenience advantage.

Sanofi claims amlitelimab could be both the first and best-in-class Ox40L-targeting project. A look at the pipeline shows there is not a lot of competition here, although Amgen’s rocatinlimab, licensed from Kyowa Kirin, is in phase 3.

This works slightly differently, hitting the Ox40 receptor rather than the ligand. However, the idea is broadly similar: the agents aim to damp down pro-inflammatory T-cell responses.

This is the mirror image of Ox40 agonist projects that have been developed – without much success – for oncology.

Another mid-stage anti-Ox40 autoimmune project is Ichnos Sciences’ telazorlimab, which that group is looking to partner; positive results from Sanofi might help the smaller group drum up interest.

Anti-Ox40 projects in autoimmune disease
Product	Company	Description	Trial details
Phase 3
Rocatinlimab (AMG451/KHK4083)	Amgen (licensed from Kyowa Kirin)	SC anti-Ox40 MAb	Rocket programme in atopic dermatitis; trials complete 2024/25
Phase 2
Telazorlimab (ISB 830)	Ichnos Sciences	SC anti-Ox40 MAb	Ph2 completed 2021; in partnering discussions
Amlitelimab (SAR445229)	Sanofi (via Kymab)	SC anti-Ox40L MAb	Stream-AD hit Jun 2023; Tide-Asthma completes Oct 2024
SAR442970	Sanofi	Anti-TNFa/Ox40L nanobody	HS Obtain in hidradenitis suppurativa completes Oct 2024
Phase 1
IMG-007	Inmagene/Hutchmed	IV anti-Ox40 MAb	Healthy volunteer study completes Jun 2023
Source: Evaluate Pharma & clinicaltrials.gov.

Sanofi has previously detailed phase 2a data on an intravenous version of amlitelimab, but not all the signs this yielded were hugely encouraging. A lack of dose response was evident, with the low dose outperforming the high dose on change in eczema area and severity index (Easi), the co-primary endpoint. And even those low-dose data did not look that impressive on a placebo-adjusted basis – although there was an unusually high Easi reduction in the placebo group, of 49%.

When the new phase 2b Stream-AD data are released, which concern a subcutaneously administered formulation of amlitelimab, investors will be looking for a dose response to emerge. All four doses tested showed a statistically significant reduction in the primary endpoint, Easi score, versus placebo at 16 weeks, Sanofi said today.

Another thing to look out for will be dropouts, with SVB analysts previously flagging a 33% discontinuation rate in phase 2a.

A lack of dose response was also seen with Amgen’s rocatinlimab in phase 2b. That project looks better than amlitelimab on a cross-trial basis, but still not as good as Dupixent or another big atopic dermatitis drug, Abbvie’s Jak inhibitor Rinvoq.

However, both amlitelimab and rocatinlimab are injected subcutaneously every four weeks, while Dupixent is given subcutaneously every two weeks. Rinvoq is a daily oral but has toxicity worries.

Notably, Sanofi is also developing an anti-TNFa/Ox40L nanobody, SAR442970, which might represent a bid for better efficacy. The group previously discontinued SAR443726, an anti-IL-13/Ox40L nanobody.

Cross-trial comparison of phase 2 data with selected atopic dermatitis projects
	Amlitelimab	Rocatinlimab	Dupixent	Rinvoq
	Ph2a (IV formulation)	Ph2b	Ph2	Ph2
Pbo-adjusted Easi reduction	31% points*	46% points**	50% points^	51% points^^
Note: All data at 16 weeks. *Low dose (200mg loading/100mg Q4W); **300mg Q2W; ^300mg Q2W; ^^30mg daily. Source: SVB note Sep 2021, company releases, Lancet & J Allergy Clin. Immunol. articles. https://www.evaluate.com/vantage/articles/news/trial-results/more-details-needed-sanofis-atopic-dermatitis-win