Oral prifemilast, a PDE4B-selective inhibitor, led to PASI 75 attainment in up to 57.4% of those with psoriasis at week 16 vs 10.8% with placebo.
Prifemilast, an investigational oral inhibitor selective for phosphodiesterase 4B (PDE4B), produced PASI 75 response rates about 5 times higher than placebo at week 16 in adults with moderate to severe
Adverse events affecting the gastrointestinal tract and central nervous system (CNS) have long limited the tolerability of the PDE4 inhibitor class.³ Prifemilast (HPP737), developed by Newsoara Biopharma, has a molecular structure designed to limit CNS penetration and slow absorption, with the aim of reducing CNS-related adverse events.¹ A previous phase 1 study described its pharmacokinetics and tolerability in healthy participants.²
The poster was presented by Lin Cai of Peking University People’s Hospital, with co-investigators from 12 Chinese hospitals and Newsoara Biopharma.¹
The multicenter phase 2 trial randomly assigned 123 adults 1:1:1:1 to once-daily prifemilast 6 mg, 10 mg or 20 mg (n = 31 each) or placebo (n = 30) for 12 weeks.¹ Participants had a mean age of 40.2 years, and 79.7% were male.
At week 12, all 3 prifemilast doses produced higher PASI 75 and PASI 90 response rates than placebo, and the response increased with dose. The differences were statistically significant for the 10 mg and 20 mg doses (P < .05).¹ Of 239 adverse events reported in 84 patients, most were grade 1 or 2 and resolved by the end of the study.
The 2-part phase 3 trial randomly assigned 505 adults 1:1:1 to once-daily prifemilast 10 mg (n = 170), prifemilast 20 mg (n = 169) or placebo (n = 166) for 16 weeks.¹ All participants then received prifemilast 10 mg or 20 mg during a 36-week extension. The mean age was 46.3 years, and 79.2% of participants were male.
At week 16, PASI 75 was achieved by 51.8% (88/170) of subjects on 10 mg and 57.4% (97/169) of those on 20 mg, compared with 10.8% (18/166) of those being treated with a placebo (P < .0001 for both doses).¹ PASI and static Physician’s Global Assessment responses were found to have separated from placebo as early as week 2.
By week 8, those evaluated also saw clinically meaningful improvements in Dermatology Life Quality Index scores, and the efficacy gains held through week 52.¹
Through week 52, most adverse events were grade 1 or 2.¹ Discontinuations due to adverse events occurred at a pooled rate of 2.8 per 100 patient-years.
Both trials enrolled patients only in China, and the abstract doesn’t report rates of individual adverse events, including gastrointestinal effects. The authors concluded that the results support further development of prifemilast as an oral therapy for psoriasis, ulcerative colitis and Crohn’s disease.¹
Editor's Note: This summary has been edited for grammar and clarity using artificial intelligence tools.
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