Can oral biologics work as well as their injectable counterparts?
An oral interleukin-23–receptor antagonist peptide that has shown similar results to its injectable counterpart in treating moderate to severe psoriasis is getting closer to reality.
Leading Australian dermatologists have joined a multi-centre international phase 3 clinical trial that will evaluate the efficacy and safety of the drug.
Professor Rod Sinclair, head of Melbourne-based Sinclair Dermatology, has begun recruiting patients for the trial. He said if the trial supported findings from studies to date, the drug could be available within three to four years.
He said it had the potential to be a game changer for needle-averse patients, but also offered other benefits when it came to medication distribution and supply and also potential cost savings.
“It’s a major breakthrough,” Professor Sinclair told The Medical Republic.
“Moving from injectables to tablets also has immediate implications for access to care, but also long-term implications to price and sustainability of the health system.”
He pointed to a paper published in the New England Journal of Medicine, which released results of a phase 2 dose finding trial of oral administration of the interleukin-23 receptor antagonist peptide (referred to as JNJ-77242113) once or twice daily for 16 weeks.
It showed superior efficacy over placebo in patients with moderate to severe plaque psoriasis, with the most significant dose-response effect at 100mg twice daily, which resulted in 79% of patients demonstrating at least a 75% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16.
Adverse events were comparable between the treatment and placebo groups, with no evidence of a dose-related increase in adverse events, the researchers found.
“The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis,” they wrote.
“The percentage of patients who had a PASI 90 response with JNJ-77242113 100mg twice daily at week 16 was 60%. In contrast, phase 3 trials of other available oral treatments showed that 27 to 36% of patients had a PASI 90 response after 16 weeks of treatment with deucravacitinib, and 18 to 20% of patients had a PASI 90 response with apremilast at week 16.
“However, without head-to-head trials, no conclusions can be drawn about the comparative efficacy of JNJ-77242113. Results from the FRONTIER 2 trial, as well as from phase 3 trials, will clarify the magnitude and durability of the clinical response to JNJ-77242113.”
The introduction of monoclonal antibodies has revolutionised the treatment landscape for immune-mediated inflammatory diseases like psoriasis. IL-23 plays a key role in the activation of pathogenic T-cells in psoriasis, making it a key target for therapeutic intervention. While several biologic agents targeting IL-23 have been approved for psoriasis treatment, their requirement for intravenous or subcutaneous administration poses challenges, particularly for patients who are needle-averse or prefer oral medications.
Dr John Frew, staff specialist dermatologist at Sydney’s Liverpool Hospital Conjoint Associate Professor, School of Clinical Medicine, UNSW and director of research at The Skin Hospital, said the dug offered exciting potential.
“It would certainly change things for those people who are less comfortable with injections, but only it’s a comparable efficacy,” he told The Medical Republic.
“The benefit of JNJ-2113 is that it’s got comparable efficacy to some of the IL-17s biologic therapies.”
He said many patients would choose an oral medication over an injection for personal choice, and it would also provide more freedom for people to travel more easily given there would be no need for cold storage. For those patients it would be a “game changer”.
Dr Frew said he would also be involved in the clinical trials through The Skin Hospital and he expected recruitment to begin in the next month or two.
Professor Sinclair said he believed rural and remote psoriasis patients across Australia would benefit greatly from the availability of an oral interleukin-23–receptor antagonist peptide.
“It also makes it a lot easier for distribution amongst pharmacies, particularly remote Australia, being able to get these things out to add to centres where you might have trouble maintaining the cold chain,” he said.
“It also opens up the possibility that the cost of these things will come down enormously, and that will increase accessibility even more.”
