Dr. Andrew Blauvelt discusses new possibilities in the psoriasis treatment pipeline, from an investigational biologic with unprecedented efficacy, to promising new oral TYK2 options and new strategies for oral drug delivery.
Andrew Blauvelt, MD, MBA, Dermatologist, Portland, Oregon, and Investigator, Oregon Medical Research Center
“I’m excited about the psoriasis pipeline. It’s different than in the past. It’s not just another biologic [although there’s one promising investigational biologic]. There are exciting pill options and different strategies for treating patients at different stages of disease,” said Andrew Blauvelt, MD, MBA, who presented during the Psoriasis Update session at Maui Derm Hawaii 2023, in Maui, Hawaii.
Bimekizumab
The biologic bimekizumab is likely to be FDA approved this summer, according to Dr. Blauvelt.
“Bimekizumab has been approved in Canada and Europe. This biologic targets interleukin (IL)-17A and IL-17F (two IL-17 isoforms). So, it’s a little bit different than the other IL-17 inhibitors.”
The studies on bimekizumab show what Dr. Blauvelt calls “terrific efficacy.”
“We actually see the highest Psoriasis Area and Severity Index (PASI) 100, or complete clearance, numbers (around 70%) that we have seen with any other psoriasis drug to date, including all the other biologics.”
“In terms of safety, this drug can cause oral candidiasis in about 15% of patients, which is a higher rate than we see with other IL-17 blockers. We think this is due to the additional blockade of IL-17F, which is particularly important for controlling Candida in the oral mucosa.”
Oral Options in the Pipeline
There are several new selective TYK2 inhibitors that are coming out on the heels of deucravacitinib (SOTYKTU, Bristol Myers Squibb), which was approved last fall as an oral therapy for psoriasis, said Dr. Blauvelt.
“Patients take deucravacitinib once a day. And now a number of companies, largely based on deucravacitinib’s success, are testing their particular TYK2 blockers to see if they have better efficacy than deucravacitinib.”
TKY2 represents a strong target for psoriasis because IL-23 uses it to signal. That means that TYK2 inhibitors block IL-23 production, said Dr. Blauvelt.
Down the Road
There are drugs in the long-term psoriasis pipeline that are likely to come out in the next 5 to 10 years, said Dr. Blauvelt.
“There is the possibility of oral biologics, and these come in two flavors. There are small molecules that block the receptor—either the IL-17 receptor or the IL-23 receptor. The companies working in this area of oral biologics hope to have medications with efficacy as high as the subcutaneous biologics but taken as a pill.”
Another oral strategy is to encapsulate monoclonal antibodies into pills that will cross the gastric mucosa and be absorbed, said Dr. Blauvelt.
“The company working on this has invented ‘robotic pills,’ where they put biologics into pill form. These are digested. Then a little robot mechanism is activated, and the actual drug is injected through the gut wall via a mini ‘digestible needle,’ so the monoclonal antibody, which normally would not get across the gut lining, can get across and into the bloodstream.”
High-Dose Knockout Therapy
Then there is the concept of “hard hit early,” according to Dr. Blauvelt.
“This means we’re trying to use high doses of biologics at earlier stages of psoriasis. Hopefully, we may see some long-term remissions and possible cures if we treat patients in this manner.”
Case-in-point, an ongoing clinical trial at Oregon Medical Research Center (ClinicalTrials.gov Identifier: NCT05283135) where Dr. Blauvelt and colleagues are using high induction doses of risankizumab (Skyrizi, Abbvie) to knockout psoriasis, he said.
Disclosures: Dr. Blauvelt has served as a speaker (received honoraria) for AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, and Sanofi, served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Union, Vibliome, and Xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, UCB Pharma, and Ventyx.
