Medimetriks’ PDE4 inhibitor, MM36, appears to be safe, well-tolerated and provides rapid itch relief when applied twice daily to pediatric and adolescent atopic dermatitis (AD) patients, according to results of a Phase 2 study.
The company expects to hold an End of Phase 2 Meeting with the US Food and Drug Administration later this year and start pivotal trials in the first quarter of 2018, with a goal of filing an NDA in the second half of 2019.
Discovered by Otsuka Pharmaceutical at its Ako Institute in Japan and in development there as OPA-15406, MM36 is non-steroidal topical anti-inflammatory PDE4 inhibitor in development for the potential treatment of AD. MM36 is believed to exert anti-inflammatory action by inhibiting the production of cytokines and chemical mediators thought to cause the signs and symptoms of AD. In particular, MM36 exhibits highly selective inhibitory activity against PDE4 subtypes, particularly sub-type B, which may play a significant role in inflammation.
The new study consisted of 32 patients with predominantly moderate or severe AD (based on Investigator Global Assessment) and mean baseline total body surface area involvement of 43.7 percent.
The study's primary endpoint was assessment of pharmacokinetic absorption under maximal use conditions for four weeks, with secondary endpoints of safety and tolerability based on local and systemic adverse events.
Overall blood concentration of MM36 was low and consistent with earlier studies. MM36 appears to be safe and well-tolerated with no serious adverse events observed during the study.
Exploratory efficacy endpoints included assessment of time to itch relief, change in sleep patterns and improvement in disease severity using several validated scales.
To evaluate the potential ability of MM36 to provide rapid itch relief, the study utilized several validated pruritus measures including the Visual Analog Scale (VAS), Numeric Rating Scale (NRS) and Verbal Rating Scale (VRS). Patients were assessed during the first 24 hours and through day 29. Results demonstrated:
- Median time to itch improvement was 5.76 hours after MM36 application as reported using VRS2
- On average, by hour 4 patients achieved a 60 percent median reduction in pruritus which was sustained at day 29, as reported by VAS
Patients also reported improvements in sleep during the study, based on both the Patient-Oriented Eczema Measure (POEM) and Scoring Atopic Dermatitis (SCORAD) scales.
Additional exploratory endpoints included measuring improvement in disease severity as measured using Eczema Area and Severity Index (EASI) scores.
- Subjects achieved a 45 percent median reduction in EASI score by day 8 of the study, and reached 66 percent improvement by day 29
- Disease on the face, head and neck showed a median EASI score reduction of 81 percent by day 29
“The Phase 2 study results of MM36 demonstrate the potential for itch relief in hours, which may improve both treatment outcomes and patient quality-of-life," said Linda Stein Gold, MD, director of clinical research, Department of Dermatology at Henry Ford Hospital. "Considering both the early itch relief and observed safety findings, it appears that MM36 could address an important unmet need in AD management.”