Topical S. aureus – Targeting Endolysin Significantly Improves Symptoms and QoL in Individuals With Atopic Dermatitis

treatments in AD adults and children. Using Endobioma as adjunctive therapy to boost efficacy of medical treatments and potentially reduce their length of use would be interesting and should be further investigated.

In this era of increasing antibiotic resistance, Endobioma mechanism of action makes it an attractive, precise, antimicrobial solution.³¹ The recognition and lytic activity are highly specific to S. aureus cell wall, excluding impact on other bacteria even within the same genus.^32,33 Unlike antibiotics, Endobioma has little risk of developing resistance.²⁶ Resistance mechanisms such as active efflux from the cell or decreased membrane permeability are avoided due to the external application.³⁴ Moreover, S. aureus membrane peptidoglycans is a highly preserved structure, difficult to alter. Last, Endobioma-triggered cell wall destruction is independent of host metabolism, so there is no pressure for the bacteria to evolve.²⁷

Our study adds new evidence to the potential and current trend to target the skin microbiome for AD management as we further understand the role of skin microbiome dysbiosis and S. aureus in its pathogenesis.¹¹ Though follow-up studies should be conducted to assess the effect of Endobioma on the skin microbiome composition, our results both show the rapid anti-S. aureus activity of the cream in vitro and its efficacy in managing AD in vivo.

The clinical improvements shown in this study confirm previous, preliminary case report of three cases of recurrent S. aureus-related dermatoses that were successfully treated with the endolysin-containing cream.³⁵ When used in a double-blind, vehicle-controlled study in conjunction with TCS, the endolysin-cream failed to demonstrate an effect on corticosteroid use (MAAS study).³⁵ However, prior to inclusion, patients were treated for 2 weeks with a moderate TCS dose, dramatically reducing their AD severity, and could continue using TCS with the endolysin-cream. Both factors could have contributed to masking the full benefit of endolysin vs vehicle. For those reasons and to really gauge the benefit of this new technology, we chose to use the Endobioma-containing cream as a monotherapy in patients with a higher initial SCORAD.

Of interest is the rapidity of the benefits observed with Endobioma. SCORAD was reduced by 43% after 7 days and 68% by 14 days. In a similar study design, the Eczema Area Severity Index (EASI) and the Atopic Dermatitis Severity Index (ADSI) were reduced by 51% and 54% after 2 weeks.³⁶ Although numerical improvement comparison is difficult with different scoring scales, our study showed an itch severity reduction of 74% at day 14 compared to 61% in the other study.

Poor adherence to AD treatment associated with side effects, treatment length or “corticophobia”, is a known problem and can lead to S. aureus recolonization and flares.³⁷ Rapidly effective, TCS-free, with an inherent respect for the skin microbiota, and without observed side effects, Endobioma cream represents an attractive AD treatment solution. Additionally, our study highlighted a good cosmetic acceptability which may improve treatment compliance, potentially reducing flares. Interestingly, in the MAAS study³⁸ the number of doctor-reported flares was lower in the Endobioma group than in the vehicle group. Altogether, these results suggest that it would be worth assessing the long-term benefits of Endobioma as a proactive therapy to prevent and reduce the occurrence of flares and assess compliance.

This study showed that S. aureus-targeting Endobioma cream monotherapy produced a statistically and clinically significant reduction of AD severity scores and improved skin sensitivity and QoL in both adults and children. Safety and tolerability were excellent, enabling Endobioma to be applied to sensitive areas, thus, constituting a good option for AD patches in children. Future investigation assessing the in vivo effect of Endobioma-cream on the skin microbiome, particularly S. aureus, and immune response markers would be interesting to further understand the interplay between skin microbiome, skin immune response and AD clinical symptoms occurrence. Since Endobioma-cream is safe and offers an opportunity to prevent S. aureus over-colonization, it may be beneficial to prevent and reduce flares.

Ann’Laure Demessant, Magali Moreau, Sophie Seité, Luc Aguilar, Olivier Da Cruz and Julia Puech are L’Oréal employees. Johan Frieling is a Micreos Human Health employee.

Funding: The in vitro study was funded by L’Oreal R & I; the clinical study was funded by L'Oreal and La Roche Posay. The study product was provided by Micreos Human Health.

The authors would like to thank Charlotte Wright, Speak the Speech Consulting, for her assistance in drafting and editing this manuscript and the Micreos team for helpful comments.

Ann'Laure Demessant PharmD anne-laure.demessant@loreal.com