BMS hep C drug approved in Europe

The news in hepatitis C in recent months has all been about Gilead's record-smashing launch of Sovaldi and whether rival AbbVie will be able to close the gap on the market leader.

Bristol-Myers Squibb (BMS) has been dismissed in some quarters as something of an also-ran, but the approval of its Daklinza (daclatasvir) as the first NS5A replication complex inhibitor in Europe could change that perception.

Launched last December, NS5B polymerase inhibitor Sovaldi (sofosbuvir) became the biggest pharmaceutical launch of all time in its first quarter on the market and shows no signs of slowing down.

A hefty $84,000-a-year price tag for the drug helped first-half sales of Sovaldi were knocking on the door of $6bn - well above what some analysts were predicting for the drug at peak a couple of years ago - as the drug met pent-up demand for a regimen that removed the need for hard-to-tolerate interferon alfa-based regimens.

That has a direct bearing on the potential for Daklinza because BMS' drug has been approved with labelling that specifically covers its use alongside Sovaldi in patients with genotypes 1, 3 and 4 hepatitis C virus (HCV) infection.

Daklinza has also been approved by the European Medicines Agency (EMA) for genotype 2 HCV, can be used even in patients with advanced liver disease such as cirrhosis and also in patients who have failed treatment with first-generation protease inhibitors.

The green light in Europe sets up an interesting scenario in which BMS can tap into Sovaldi's growth before rival Gilead can bring a fixed-dose combination of Sovaldi and its own NS5A replication complex inhibitor ledipasvir to market.

Gilead clearly wants doctors to prescribe its own combination product after it is approved - likely later this year in both Europe and the US - and refused to take part in the combination trials of Daklinza and Sovaldi.

It should be pointed out that Europe accounts for a minor share of Sovaldi's overall sales, with its take-up hampered by the time it takes to negotiate and secure reimbursement in many EU countries.

Nevertheless, BMS' chief commercial officer Giovanni Caforio said recently he believes that Europe will be a key market for daclatasvir " because of the existence of segments of the population ...that are particularly well suited to the use of daclatasvir in combination with sofosbuvir", as well as potentially other agents in the pipeline.

In trials, the combination of the two drugs achieved a 100% cure rate in as little as 12 weeks, compared to 48 weeks for interferon-based therapies and - according to BMS' head of worldwide commercialisation Emmanuel Blin - "will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices."

In the US the situation is more complex, as BMS filed for approval for daclatasvir alongside its NS3 protease inhibitor Sunvepra (asunaprevir), and was not able to submit the combination data with sofosbuvir. The data on the Daklinza/Sunvepra combination does not seem quite as compelling so, short of off-label prescribing which could be unlikely given the attention already being paid to the cost of Sovaldi - Gilead's fixed-dose offering looks likely to dominate in the US.

Meanwhile, in yet another twist in the tale, Daklinza has already been approved for use in Japan alongside BMS' NS3 protease inhibitor Sunvepra (asunaprevir) as the first interferon-free regimen. Japan is a key HCV market as it has 1.2 million hepatitis C sufferers, and it is interesting how regulatory timelines are splitting the HCV market ahead of direct competition in the marketplace for the new generation of drugs.

AbbVie also remains a strong competitor-in-the-offing with its three-drug, fixed combination of ABT-450/ritonavir, ombitasvir (ABT-267) and dasabuvir, which could reach the market in Europe and the US early next year, and Merck & Co is also ushering its own combination through late-stage development. It will be fascinating to see how the marketing battle plays out over the next couple of years.

Image: courtesy of Shutterstock/klublu