Delay to hep C drug program behind Merck's write-down decision, say analysts

Merck & Co.'s decision to write down the value of hepatitis C drug therapy uprifosbuvir and absorb a whopping $2.9 billion charge reportedly comes on the back of regulatory requests for additional clinical trials.

In a research note, Leerink indicates that the main reason for making the impairment decision right now stems from regulators asking for data from other studies before it can press ahead with a phase 3 program for uprifosbuvir.

That puts a question mark over the timing of pivotal studies, which will combine the drug in a triple regimen with two other Merck compounds, and sets back a possible launch date for the drug at a time when the overall market for hepatitis C virus (HCV) therapies is shrinking thanks to a declining eligible patient population and a more difficult pricing environment.

Merck's development plans for uprifosbuvir (MK3682)—a nucleotide ('nuke') NS5b polymerase inhibitor acquired along with the rest of Idenix for $3.9bn in 2014—is to combine it with two of its other HCV drugs in a cocktail that can be used in all patients, regardless of their virus genotype.

Uprifosbuvir has a similar structure to Gilead Sciences' Sovaldi (sofosbuvir) and is in multiple trials alongside Merck's NS3/4A protease inhibitor grazoprevir, one of the components in Merck's two-drug Zepatier product, and experimental NS5a blocker ruzasvir (MK8408).

According to Leerink, Merck has been told by regulators it will have to "complete separate trials, and show an added benefit" with the triple therapy over a high-dose doublet therapy based on uprifosbuvir and ruzasvir that is further behind in development.

"This suggests that company will need to wait for data from the high-dose doublet (which is…in phase 2) and delays the timing of the triple materially," the analysts write. Data from that phase 2 trial isn’t due until later this year, so Merck's hopes of an accelerated path to market for the triple therapy seem to have been dashed.

With only doublet therapy in play Merck will likely lose out to rivals Gilead and AbbVie between 2018 and 2021, they suggest.

Meanwhile, it seems that another nuke acquired in the Idenix deal called IDX21459 is not in active development, while a third HCV asset—NS5a  inhibitor samatasvir—was discontinued in 2015.