Moberg Pharma has completed the expert evaluation of the results from the North American Phase 3-study.
The analysis conducted with key opinion leaders (KOLs) has confirmed the validity of the data presented in December 2019 and increased the understanding of the study outcomes.
Key conclusions include: i) MOB-015 delivers a very high mycological cure rate that compares favorably to oral antifungal drugs with the added advantage of an earlier onset of action; ii) Confirmation that the proprietary vehicle technology increases the hydration and permeability of the nail plate enabling efficient terbinafine delivery, however it also confounds the assessment of clinical cure and complete cure and iii) A likely solution to the problem – a shorter dosing regimen with the potential to deliver superior complete cure rates.
A solution for the problem was identified
The company has engaged leading key opinion leaders to help Moberg Pharma verify the results presented in December 2019 and better understand the reasons for the conflicting outcome. The key question for the KOLs has been to help the company understand why the high mycological cure did not result in high complete cure. The KOLs found the mycological cure rate of MOB-015 remarkable and very exciting, as the first topical treatment with mycological cure rate at the same level as oral terbinafine, the current gold standard for treatment of onychomycosis. Furthermore, the onset of the antifungal effect is more rapid than for oral terbinafine, with MOB-015 delivering 55 percent mycological cure at 6 months (vs 40 percent for oral terbinafine) and 37 percent already at 3 months (vs 15 percent for oral terbinafine). In addition, after detailed analysis of the data and individual photos from the study, the KOLs concluded that while the vehicle technology enables high delivery of terbinafine through the nail plate, its hydrating properties also cause whitening/discoloration in nails. This phenomenon is transient but makes the assessment of clinical cure challenging and contributed to the low complete cure rate observed.
A solution to the problem was identified in collaboration with the KOLs. Analysis of the available clinical data, including data from the recent Phase 3 study, earlier Moberg Pharma studies as well as from the literature, the KOLs as well as the company experts conclude that the complete cure rate for MOB-015 likely can be increased substantially by a shorter treatment period followed by a maintenance period.
The current gold standard in onychomycosis is three months treatment with oral terbinafine. Before this phase 3 trial for MOB-015, it appeared unrealistic that a topical treatment would achieve 70 percent mycological cure rate – the same level as oral terbinafine. Treatment with MOB-015 resulted in 1000x higher amounts of terbinafine in the nail plate and 40x higher in the nail bed compared to oral terbinafine treatment. Considering also the rapid onset and high mycological cure rate, the data indicates that a shorter dosing regimen has the potential to increase complete cure rates. The KOL evaluation concludes that once-daily treatment period for not more than three months, followed by maintenance dosing once weekly until week 48 should maintain high concentrations of terbinafine in the tissue, while reducing the hydrating effects after the initial treatment phase and thus the impact on the clinical cure assessment at week 52.
A basis to register the product
Since the primary endpoint as well as secondary endpoints were met in the North American trial and provided that the second study also produces positive results, these studies could form a basis to register the product. The timing to optimize the dosing regimen will depend on the outcome of the EU trial.
“From a medical and commercial perspective, a regimen with daily dosing for up to three months followed by less frequent treatment, is highly attractive and further improves the target product profile of MOB-015. This is further supported by U.S. market data indicating that real-life usage of current topicals on average is 3-4 months, despite being labeled for 48 weeks’ daily treatment”, said Dr. Amir Tavakkol, CSO of Moberg Pharma AB.
“We are very grateful for the thorough analysis of the key opinion leaders which not only shed light on the conflicting data points, but also strengthened our conviction that MOB-015 has the potential to become the future market leader in onychomycosis”, said Anna Ljung, CEO of Moberg Pharma AB.
Photo of Anna Ljung: Moberg Pharma