Vertex Pharmaceuticals Inc. will add the FDA’s most serious warning to the US label of the Cambridge company’s best-selling drug, Incivek, following reports that at least two patients died from severe skin reactions after taking it in combination with two other hepatitis C treatments.
The so-called black box warning — it is bordered in black — is designed to give more prominence to existing label language and to the way Incivek-related skin rashes should be treated.
Vertex urges physicians to halt the three-drug combination and provide urgent medical care when serious skin rashes crop up in Incivek patients, especially irritations that grow worse, cover more than half the body, or are accompanied by fever, diarrhea, or mouth sores.
The deaths, which came when patients continued treatment after an adverse skin reaction, were reported separately Wednesday by Vertex and the FDA. Company executives cited “a small number of fatalities” but wouldn’t say how many.
Food and Drug Administration officials said there were two known deaths, including a 47-year-old woman in the United States and 69-year-old man in Japan. They also reported 112 nonfatal “adverse events” stemming from two types of skin reaction to the combination treatment.
Incivek, the first drug developed solely by Vertex, was approved in 2011 for sale in the United States, where it already had been prescribed to more than 50,000 patients in conjunction with the established hepatitis C treatments peginterferon alfa and ribaviran. Incivek is also sold in Canada, Europe, Japan, and some countries in South America.
Vertex shares fell 0.7 percent to $43.02.
A patient advocate said the enhanced warning is important but shouldn’t discourage hepatitis C patients.
“Obviously, any time you hear something scary like that, it concerns patients,” said Lorren Sandt, executive director of Caring Ambassadors, an Oregon nonprofit that supports patients with hepatitis C and other chronic diseases. “But this is a known side effect, and the action that needs to be taken is also known. This shouldn’t be a reason for people not to go on therapy if they need to.”
Dr. Robert Kauffman, chief medical officer at Vertex, said the decision to add a black box warning was made jointly by the company and FDA.
“The safety of patients is our highest priority,” he said. “We were concerned, as they were, that the combination treatment was being continued after skin rashes were seen.”
Skin rashes have long been identified as potential side effects of Incivek and were listed as suchon its original label. The black box is a way “to raise the prominence of the warning and to reiterate that the treatment should be stopped in the case of these serious skin reactions,” Kauffman said.
The FDA typically seeks boxed warnings if there is “risk of an adverse reaction that can be prevented or reduced in severity by appropriate use of the drug,” including carefully monitoring patients, said spokeswoman Stephanie Yao.
Yao said the agency has not considered pulling Incivek from the market. The Incivek drug combination so far has proven effective in treating the hepatitis C virus, which is spread through contact with the blood of infected people and can cause potentially fatal liver disease.
“The FDA believes that the potential benefits of Incivek combination therapy, namely reduction in morbidity and mortality from the complications of chronic hepatitis C infection, outweigh the potential risk of mortality from serious skin reactions,” she said.
The agency is also convinced that “informing health care providers about the importance of prompt discontinuation of Incivek combination therapy and the need for urgent medical care when patients develop rash with systemic symptoms or progressive rash while taking Incivek combination therapy can mitigate the risk of death from this event,” Yao said.
Analysts said it may be too soon to assess how the boxed warning and the deaths from serious skin reactions will affect Incivek sales. In its most recent quarter, Vertex reported that it accounted for $254 million of the company’s $336 million in revenue.
Doctors can become more cautious about prescribing a drug when a company adds a tougher warning label, though many stick with effective treatments and manage side effects, said Harry Glorikian, managing partner at a Cambridge life sciences consulting firm, Scientia Advisors.
“It might mean that there has to be more education for physicians to make sure there are no dips in sales,” Glorikian said. “They learn how to manage the conditions on the warning.”Robert Weisman can be reached at firstname.lastname@example.org.