Vertex Pharmaceuticals has added a boxed warning to the label of its oral hepatitis C product Incivek after multiple deaths caused by skin reactions.
According to the company “fatal cases of serious skin reactions have been reported in patients with progressive rash and systemic symptoms”, although it noted deaths occurred in patients who continued to receive Incivek (telaprevir) as part of a combination regimen after the skin reaction was first identified.
The reactions have been observed in two patients from Japan who took Incivek alongside peginterferon alfa and ribavirin, which is the approved regimen for the drug, said the FDA in a safety alert.
The two patients developed a reaction known as toxic epidermal necrolysis (TEN), and in one case the side effect proved fatal.
Incivek’s label already contains information on the risk of serious skin reactions, and there have been cases in which these caused patient hospitalisations and deaths in the past, said the agency, which recommend that any patient suffering a serious skin reaction should discontinue all three drugs used in Incivek combination therapy.
“In phase III clinical trials, less than 1 per cent of people who received Incivek combination treatment experienced a serious skin reaction,” said Vertex in a statement.
“The safety of people taking our medicines is our first priority, and we are committed to ensuring that patients and physicians are aware of the label update,” added the firm’s chief medical officer Robert Kauffman.
Incivek is partnered with Johnson & Johnson in the US and was launched there last year. It is a key product for Vertex at the moment, having already been used in more than 50,000 hepatitis C patients since its launch, and is expected to achieve sales of up to $1.25bn in 2012.
That said, Incivek’s importance is already on the wane as Vertex and its rivals develop all-oral hepatitis regimens which do not need to include interferon. Third-quarter sales of the drug were down 40 per cent compared to a year ago at just over $250m, and 25 per cent shy of the prior quarter.
The cornerstone of Vertex’ all-oral regimens is VX-135, a nucleotide polymerase inhibitor that is being tested alongside a range of other directly-acting antivirals, including GlaxoSmithKline’s NS5A inhibitor GSK2336805 and Johnson & Johnson’s protease inhibitor simeprevir. Vertex is, however, also planning to test VX-135 with Incivek and its own protease inhibitor VX-222.
Meanwhile, a number of other companies are also bringing new hepatitis C agents to market – notably Gilead Sciences with its sofosbuvir (formerly GS-7977) and Abbott Laboratories (AbbVie) with ABT-333 – as part of oral treatment regimens.
There is evidence that patients with less severe hep C infections are deferring treatment with Incivek and rival drug Victrelis (boceprevir) from Merck & Co until all-oral regimens become available, which is dampening sales growth.