New evidence shows that systemic inflammation in psoriasis can be treated orally with a non-living strain of a commensal microbe
Disruptive innovations in psoriasis are leading the way at EADV’s 29th Congress, EADV Virtual. New data published today shows the first clinical evidence of modulating systemic inflammation by oral delivery of a non-living single strain commensal microbe. This new therapeutic class brings hope for a completely new way of treating this debilitating skin condition.[i]
The phase 1b clinical study, by Evelo Biosciences, evaluated EDP1815, a preparation of a non-living single strain of the bacterium Prevotella histicola, isolated from the small intestine of a human donor, in two cohorts of 12 and 18 patients with mild to moderate psoriasis for 28 days, with follow-up off treatment through 42 days. EDP1815 is an orally-delivered investigational therapy that is being developed for treatment of inflammatory diseases but has never been used for a human disease before.
The small intestine plays a central role in governing the body’s immune, metabolic and neurological systems. When the oral microbe is administered, it interacts with a network of connections between the small intestine and the rest of the body, creating a systemic therapeutic immune response, without being absorbed into the body. This physiological mechanism of control has not been shown to cause any immune suppression, further reducing the risk of side-effects such as infections.
Early results showed that EDP1815 was well tolerated at daily doses of up to 8.0x101 cells administered for up to 28 days, with a tolerability profile comparable to placebo, with no serious adverse effects reported. At day 28, the mean percentage reduction in Psoriasis Area Severity Index (PASI) score for both EDP1815 cohorts was 16%, compared to 1% for placebo; with a further improvement to 21% in the high-dose cohort at day 42, but not the low dose cohort (10%) or placebo cohorts (3%). This is indicative of sustained and ongoing clinical effect at the higher dose. The mean reduction in Lesion Severity Scores (LSS) at 28 days were 15% and 23% in the high- and low-dose cohorts, respectively, compared to a 1% increase from baseline in the placebo group. Again, further clinical improvement, to a 24% reduction, was seen in the high-dose cohort.
Dr Douglas Maslin, Dermatologist and Pharmacologist at Addenbrooke’s Hospital in Cambridge, UK working on secondment with Evelo Biosciences explains: “Although several treatments options are available for psoriasis patients with the most severe disease, there is a great need for new innovative methods for those living with mild-moderate disease. I decided to work with Evelo Biosciences after seeing the huge potential in EDP1815 and its oral mechanism of action. It is a real breakthrough, especially as we have seen from the pre-clinical and phase I trials that it was well tolerated with no overall difference from placebo and with no severe side effects reported. We are extremely encouraged to see that these data support further clinical development of EDP1815 in psoriasis. We are already in phase II clinical trials across the UK, Poland and US. This is a potentially massive win for the majority of psoriasis patients, as it has the potential to improve treatment options and perhaps change the current standard of care.”
New guidelines and promising treatments in psoriasis at EADV Virtual
This year’s EADV Virtual, which launches on World Psoriasis Day, will showcase some of the cutting-edge innovations and trends in psoriasis and key updates in the field. Today, this includes a presentation from Professor Dr Rolland Gyulai from Hungary, who will be sharing the new 2020 European and US guidelines and discussing the latest clinical trials and where there is still a place for classical systemic treatments.[ii]
Also, Associate Professor Eniko Sonkoly from the Department of Medicine Solna, Karolinska Institute/ Karolinska University Hospital Solna in Sweden, will be presenting a review of the existing and upcoming pipeline of small molecules that show great potential in managing and treating the condition.[iii] Professor Sonkoly explains: “Although there are many effective biologics, they are not suitable for all patients with psoriasis. There is a need for new oral and topical treatments with favourable safety profiles that can benefit mild, moderate and severe patients, improving their quality of life. Small molecules have the advantage of being suitable for both oral and topical delivery and have the potential to improve available treatment options.”
[i] Maslin D, Carpenter N, Dutta P et. al. SAFETY AND EFFICACY OF AN ORALLY ADMINISTERED, SINGLE STRAIN COMMENSAL MICROBE IN PSORIASIS AFTER 28 DAYS OF THERAPY: EDP1815 Abstract no 2039 EADV Virtual, 29-31 October 2020.
[ii] Gyulai R. When to use classical systemic treatment, EADV Virtual, 29 October 2020. Inflammatory diseases: Psoriasis session, 11:15-11:30:
[iii] Sonkoly E. Existing and upcoming small molecules, EADV Virtual, 29 October 2020. Inflammatory diseases: Psoriasis session, 12;00-12:15