In the following, I will leverage Trialtrove and Pharmaprojects data to assess 2017 trial initiations focused on non-alcoholic fatty liver disease (NAFLD), including the subtype non-alcoholic steatohepatitis (NASH). This analysis will include an initial wide glance at the trial landscape, focusing down to industry-sponsored trials in NASH.
As of May 21, 2018, in total there were 89 trial initiations in 2017 focused on the treatment of NAFLD. Of these trials, 55 percent (49) are industry sponsored trials, representing an increase in industry-sponsored trial starts of 9 percent as compared to the previous year (Figure 1).
Figure 1. Industry-sponsored trial starts for non-alcoholic fatty liver disease treatment
Source: Trialtrove® May 2018
As NAFLD is more prevalent in developed countries, it is not a surprise that the United States is a study site location in 28 of the 49 industry-sponsored trials initiated last year, which is by far the most with Australia next in line with 11 trials. Also, the United States was the only study location for 31% (15) of industry-sponsored NAFLD trials (Data not shown).
Phase I-II trials dominated, comprising 80% of the industry-sponsored trials. Phase III trials represented 12% of these trial starts in 2017. The majority (59%) of industry-sponsored trials are currently recruiting participants. The same percentage of trials focus on the treatment of NASH (59%) (Data not shown).
The leading companies for NAFLD activity in 2017 include Pfizer with seven trials, Boehringer Ingelheim with four trials, and Allergan and Enanta, which sponsored three trials each (Figure 2). Additionally, Gilead, Ionis Pharmaceuticals and Zydus Cadila initiated two trials each (Data not shown).
Figure 2. Top sponsors of industry-sponsored non-alcoholic fatty liver disease trials initiated in 2017
Source: Trialtrove®, May 2018
In the set of trials by the top sponsors currently working in this area, there are four compounds being evaluated in the seven trials sponsored by Pfizer. Of the seven trials, five are focused on NASH. Four of the trials are Phase I trials, with one being a Phase IIa for PF-05221304. The four trials sponsored by Boehringer evaluates their VAP-1 antagonist, BI 1467335, currently in Phase II development. Of these trials, three are Phase I and only the Phase II trial focuses on NASH. All trials sponsored by Enanta are Phase I, focus directly on NASH and involve the compound EDP-305. Two of three trials sponsored by Allergan focused on NASH using cenicriviroc, including the Phase III registration trial, AURORA, with a large target enrolment of 2,000 participants.
Moving to later phase activity, saroglitazar from Zydus Cadila, is involved in two trials, a Phase II and III, neither of which are in NASH patients. Gilead’s two trials focus on NASH, both Phase III and involve the compound selonsertib, including the registration trial, STELLAR 4, in which Gilead announced enrollment completion in February 2018 []. These trials involving selonsertib represent 40 percent of the industry sponsored Phase III NASH trials initiated in 2017. Ionis’ two trials are Phase II and involve two different compounds. One is the angiopoietin-like 3 inhibitor, IONIS-ANGPTL3-LRx and the other is IONIS-DGAT2Rx a DGAT2 inhibitor.
In total there are seven industry-sponsored Phase III trials in the NAFLD space, of which five focus on NASH. In addition to the four Phase III trials mentioned above, the three remaining trials include two focused on NASH: Conatus Pharmaceuticals’ Phase II/III ENCORE-LF trial involving emricasan and the registration trial, REVERSE involving Genextra/Intercept Pharmaceuticals’ obeticholic acid. The final trial, TONKA-V3, is sponsored by Vietnam based Nhat Nhat Pharmaceutical Company and involves an unidentified compound focusing on a number of liver function disorders, including NAFLD. Overall, there are currently nine compounds in Phase III development for the treatment of NAFLD/NASH (Table 1).
Table 1. Drugs in Phase III development for non-alcoholic fatty liver disease
Source: Pharmaprojects ®, May 2018
In conclusion, research continues to increase in the NAFLD/NASH disease area as companies try to gain approval for their compounds and become the first to be approved for NAFLD/NASH, with Phase III development heating up in 2017-18. Three of the major players in the race, Allergan, Gilead and Genextra all initiated registration trials in 2017. These initiations represent 50 percent of the total ongoing registration trials in the NAFLD space. Currently within the entire NAFLD space, there are six ongoing and two planned registration trials. With Gilead completing enrollment in their registration trial, STELLAR 4, the company is in good position to be first for approval in the NAFLD market space. As there are two registration trials in the NAFLD space scheduled to initiate later in 2018, the second half sets up to be an exciting time as we watch this race for the first approval continue.