Summary
- The entire NASH space was shaken by Genfit's trial fiasco; Viking has its own problems.
- The drug may actually be a wonderful new therapy for NASH/NAFLD patients; however, whether VKTX will benefit from it remains to be seen.
- Patent expiry and competitive delay compared to Madrigal are my main concerns.
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I covered Viking Therapeutics (NASDAQ:VKTX) in August last year. Since then, there have been a few developments. This article covers those.
The first thing to understand here is that Madrigal (NASDAQ:MDGL) - which I covered recently - and Viking are working with drugs with the same basic mechanism of action. Both resmetirom and VK2809 are selective THR-? agonists that target a key receptor common to a spectrum of cardio-metabolic and fatty liver diseases. But the similarity ends there. Madrigal is in a much advanced clinical development stage - by some accounts between four and five years ahead - and the drug may actually be approved in NAFLD within a year or so. It is currently running a set of two phase 3 trials in NAFLD and NASH.
Viking, on the other hand, has completed a phase 2b trial in NAFLD - with excellent results - and last year began a phase 2b NASH trial. This trial will be completed in November 2021. It has an endpoint similar to Madrigal’s - relative change in liver fat content (assessed by MRI-PDFF) - which, studies have shown, is a good surrogate endpoint for resolution of fibrosis. Already in Madrigal studies, we saw how reduction of liver fat content by 30% or more positively affects fibrosis. So, this trial will be looking at that.
One problem we notice is in recruitment. While Madrigal’s biopsy-based liver trials are getting fully enrolled quite quickly, Viking’s are taking longer. Liver biopsy is a painful invasive procedure, and patients are probably trying to line up for the trial that will give them an approved drug sooner. Or maybe Madrigal’s outreach is just better - I do not know. But I note that Madrigal’s 700-patient phase 3 MAESTRO NAFLD trial got fully recruited two months ahead of schedule, while Viking’s 337-patient NAFLD trial is still recruiting after one year.
So, if we have two drugs with the same mechanism, one five years ahead in clinical development over the other, why should we even bother with the other drug? What Viking bulls have tried to project is the allegedly better safety and efficacy profile of VK2809 over resmetirom. Given that there has been no head-to-head comparison, this is a tough one to digest. However, let’s look at the comparative differences in the two molecules to figure out if VK2809 is worth the wait.
I actually covered this extensively in August 2018 - and since the molecules are still the same, much of what we discussed that day is still valid. That article had an extensive reader discussion which shed a lot of light on the topic of comparative differences between VK2809 and MGL-3196. You should read it. The principle differences are:
Higher affinity - For MGL-3196, it has been said that it has a 28-fold higher affinity to TR? than to TR?, while the activated form of VK2809 has approximately 16-fold higher affinity for TR? (Ki = 2.2 nM) than for TR? (Ki = 35.2 nM).
More LDL-C reduction - IMB07811 decreased LDL cholesterol (41%), triglyceride (78%), ApoB, and Lp(A) levels while for MGL-3196, LDL cholesterol was reduced up to 30% and triglycerides up to 60%.
Possible ALT-elevation - A Viking study showed possible ALT elevation, but analysis showed that the way this was described may have been non-systematic.
