For drugmakers searching to find a treatment for non-alcoholic steatohepatitis, a chronic liver condition commonly known as NASH, questions still outnumber answers.
What's become clear, however, is that a therapeutic solution will require several complementary approaches, rather than a single cure-all drug.
While four companies — Intercept Pharmaceuticals, Gilead Sciences, Genfit and Allergan — have advanced experimental NASH treatments into Phase 3 testing, the field remains open.
"None of these drugs are so effective that it is clearly going to own the market," Raymond James analyst Steven Seedhouse said in an interview with BioPharma Dive. "There's room to improve on response rates and, because most of these drugs are pills, there's room to combine them."
At this year's Liver Meeting, which kicks off today in San Francisco and runs through Tuesday, NASH researchers and investors will get a closer look at a second wave of biotechs currently advancing earlier drug candidates through mid-stage studies. Results presented at the conference will help clarify the potential of those therapies and could serve as a catalyst for fresh dealmaking.
The 2018 edition of the Liver Meeting will also serve as a prelude to next year, when three of the four NASH front-runners are expected to read out late-stage data. Success by any could lead to the first approved therapy for the complex disease.
2019 will offer first look at Phase 3 NASH results
|Developer||Drug name||Trial(s)||Key measurement||Results expected:|
|Intercept||obeticholic acid||REGENERATE||Tests both approvable endpoints set out by FDA||H1 2019|
|Gilead||selonsertib||STELLAR 3, STELLAR 4||Fibrosis improvement w/o worsening of NASH||Q1 2019 (Stellar 4), Q2 2019 (Stellar 3)|
|Genfit||elafibranor||RESOLVE-IT||NASH resolution w/o worsening of fibrosis||End of 2019|
|Allergan||cenicriviroc||AURORA||Fibrosis improvement w/o worsening of NASH||No guidance from company|
SOURCE: Companies, clinicaltrials.gov
NASH stems from the steady build-up of fat in the liver, which can trigger inflammation and, eventually, scarring and cirrhosis. Estimates of the condition's prevalence vary widely from as low as 3% of the U.S. adult population to as much as 12%.
By some projections, NASH could become the leading cause of liver transplant in the U.S. by 2020 — making it a potential public health crisis in the making.
For that same reason, investment by pharmaceutical companies into NASH research has surged over the past several years, as analysts predict a market opportunity worth billions.
The disease's roots, however, are complex — the disease is associated with obesity, diabetes and dyslipidemia. Clinical results to date suggest combination treatments will likely be needed to fully treat the characteristic inflammation as well as the resultant liver fibrosis.
"I think everyone understands that it will either be monotherapy or combination therapy, and there will be room on the market for several different drugs," said Dean Hum, chief operating officer at Genfit, in an interview with BioPharma Dive.
In that respect, the emerging field of NASH therapies may differ from that of hepatitis C, dominated by one or two drugmakers with highly effective pills that essentially "cure" the viral liver disease.
That's a good thing for the handful of biotechs looking to prove the merit of their own NASH pipelines. At the liver meeting, attention will turn in particular to Madrigal Pharmaceuticals, Viking Therapeutics and Galmed Pharmaceuticals, along with several other companies. All will present varying levels of Phase 2 data that could inform the direction of the field.
Drug candidates to watch at this year's Liver Meeting
|Developer||Drug||Results expected||Presentation date|
|Madrigal||MGL-3196||36-week biopsy data for THR-beta agonist in NASH||Monday, Nov. 12|
|Galmed||aramchol||52-week data for SCD1 inhibitor in NASH||Tuesday, Nov. 13|
|Viking||VK-2809||12-week data for THR-beta agonist in NAFLD*||Monday, Nov. 12|
|Gilead||GS-9674||24-week data for FXR agonist in NASH||Friday, Nov.9|
|NGM Bio||NGM-282||12-week biopsy data in NASH||Sunday, Nov. 11|
*NAFLD = non-alcoholic fatty liver disease, a precursor to NASH SOURCE: Companies, AASLD abstracts
Madrigal's presentation in particular will likely be a focus for investors. The biotech's thyroid receptor beta agonist MGL-3196 is seen as one of the more promising assets moving through clinical testing, although doubts have emerged recently — particularly after Viking Therapeutics posted preliminary data suggesting its similar-acting drug could rival MGL-3196.
Dealmaking in NASH has remained on the smaller side, with a steady drumbeat of licensing deals and research collaborations. But larger pharma companies have taken note of both the opportunity and the field's progress to date.
"I think there is good interest from big pharma, which was not the case when we started, when Intercept started," said Genfit's Hum.
Just recently, for example, Novartis partnered with Pfizer to study early-stage combinations of their respective NASH drugs.
Wall Street is hoping that interest yields sizable M&A, potentially as business development teams digest the results to come from over this weekend.
"We also see the potential for M&A including post recent positive Phase II data from [Madrigal], [Viking] and others where these "small" companies (headcount wise) could benefit from resources and capital of larger companies especially when it comes to enrolling gigantic global Phase 3 studies," wrote analysts from Jefferies in an Oct. 7 note to investors.
As pipelines mature, however, valuations for companies like Intercept and Madrigal have grown, making any prospective buyout more pricey.
“Pharma, I think, is willing — to date — to take a measured approach: see which mechanisms work, see where they want to invest, develop a pipeline of early-stage assets and let the market unfold," explained Raymond James' Seedhouse.
Come next year, Phase 3 results could either accelerate or validate that wait-and-see approach.