Analysis Of The Non-Alcoholic Steatohepatitis Drug Pipeline & Market
By Mavra Nasir, Ph.D., Crystal Hsu, and Peter Bak, Ph.D.
The economic and health burden of the growing NASH population in the U.S. is a matter of immense concern, given that NASH is expected to become the leading indication for liver transplants in the U.S. in the next few years for patients with and without HCC
There are no disease-specific approved drugs for NASH, with multiple historical failures creating a substantial unmet need for the patient population
Given the complex and poorly understood nature of NASH, there are a variety of mechanisms of actions under investigation by biopharma
The first wave of NASH drugs are all expected to be monotherapy treatments with the FDA’s current refusal to grant obeticholic acid accelerated approval intensifying the race to the finish line for several late-stage agents
Based on current clinical trial guidelines, the FDA requires biopsy confirmed success in at least one of the following endpoints to grant accelerated approval: 1) improvement of ≥1 stage in fibrosis with no worsening of NASH; 2) improvement in NASH resolution with no worsening of fibrosis. In contrast to the FDA, the EMA draft guidance requires efficacy in both endpoints in a co-primary fashion, which may complicate timely approvals in the five major European markets (Germany, France, Spain, Italy, UK)
On top of the regulatory challenges, the first wave of NASH therapies will face unchartered reimbursement territory; and any novel therapy may encounter strict prior authorization from payers tied to the enrollment criteria of pivotal trials
With a flurry of deal activity in NASH during the 2016-2017 timeframe, recent clinical setbacks may have a cooling effect on the deal making. However, approval and success of OCA could reinvigorate the deal space as commercial entities look for a fast follower advantage
Key remaining areas of unmet need and future development include successful development of non-invasive diagnostics to monitor NASH progress and evaluate response to treatment, combination regimens to manage NASH and the associated comorbidities, and more clinical trials focusing on the severe F4 patients