The Dark Side of Telaprevir

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In the spring of 2011, the arrival of telaprevir (Incivek) on the market seemed to be a big win for the Hepatitis C community. Approved by the FDA to treat Hepatitis C in unison with interferon and ribavirin, telaprevir appeared to improve treatment success rates in a shorter period of time without adding any substantial safety concerns. However, it was just a matter of time before the safety profile of telaprevir showed its true colors.

Developing new drugs for a hard-to-treat illness like chronic Hepatitis C is far from a simple process:

1. Experiments and analysis suggest potential new drugs.
2. An educated hypothesis is made.
3. Millions of dollars in research and development back the hypothesis.
4. Data is collected and analyzed.
5. If proven safe and effective, the task of getting the drug approved and available to the public begins.

The drug development process typically takes many years, sometimes a decade or more, until improved medications become available to the public. Chronic Hepatitis C is a prime candidate for getting through these steps a bit quicker than usual. This is because Hepatitis C is:

• Very prevalent – over four million infected Americans, about 150 million worldwide.
• Precarious – can lead to fatal illnesses like cirrhosis and liver cancer.
• Stubborn – very hard to treat; before telaprevir and the other protease inhibitor became available, Hepatitis C treatment success rates hovered around 50 percent.

In 2005, Vertex Pharmaceuticals was granted Fast Track designation by the Food and Drug Administration (FDA) for telaprevir. In mid-2010, as part of the Fast Track designation, Vertex began to submit completed sections of the new drug application for review by the FDA on a rolling basis rather than wait until every section of the application was complete. Although telaprevir was fast-tracked, the standard safety evaluations were not rushed. Unfortunately, the side effects of any potent drug may not be thoroughly vetted for quite some time after it is on the market.

Today, telaprevir is still used as a component of Hepatitis C therapy for qualifying individuals. In combination with peg-interferon and ribavirin, telaprevir is indicated for the treatment of chronic genotype 1 Hepatitis C virus infection in adults with compensated liver disease, including cirrhosis, who are treatment-naive or who already have received interferon-based medications. Telaprevir is associated with some disturbing side effects, including:

• Nausea/vomiting
• Change in ability to taste
• Rash/blisters
• Skin or mouth sores
• Itching
• Red, swollen, itchy or teary eyes
• Hemorrhoids
• Discomfort, burning, or itching around the anus
• Dizziness/shortness of breath
• Tiredness/weakness

According to Vertex Pharmaceuticals, less than 1 percent of patients receiving telaprevir combination treatment experienced a serious skin reaction in Phase 3 clinical trials. All were hospitalized, and all recovered. Despite the encouraging data collected from intensive safety trials before the drug became available, telaprevir is now known to be capable of causing serious or life-threatening skin reactions.

Over a year and a half after being approved by the FDA, the label for telaprevir was amended in December of 2012 to contain a black box warning about the risk for serious and sometimes fatal skin reactions. According to this relatively recent label change, patients must stop taking telaprevir along with its partner drugs peg-interferon and ribavirin if they experience a serious skin reaction – particularly a rash with systemic symptoms, or a progressive severe rash.

The boxed warning states that patients receiving telaprevir in combination treatment have experienced skins reactions that include these severe conditions:

• Stevens-Johnson syndrome
• Drug reaction with eosinophilia and systemic symptoms
• Toxic epidermal necrolysis

The fatal cases occurred in patients who continued to take the drug after developing a progressive rash and systemic symptoms.

The worst-case outcomes from telaprevir side effects are horrendous, but relatively rare. Nonetheless, the common side effects known to accompany telaprevir use are severe enough to significantly impair one’s quality of life.

Rarely does a potent drug have a sparkling clean safety record. Choosing whether or not to begin a rigorous drug treatment program often involves choosing the lesser evil. In the case of chronic Hepatitis C, that choice might be between severe liver disease and telaprevir’s side effects. If choosing combination therapy with telaprevir is your best option, make sure you are fully informed of its side effects – so that you can make adjustments to your treatment regimen if necessary.

References:

http://investors.vrtx.com/releasedetail.cfm?ReleaseID=532555, Vertex Completes New Drug Application for Telaprevir for Hepatitis C, Retrieved April 21, 2013, Vertex Pharmaceuticals Incorporated, 2013.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm256299.htm, FDA Approves Incivek for Hepatitis C, Retrieved April 21, 2013, US Department of Health and Human Services, 2013.

http://www.medscape.com/viewarticle/776403, Telaprevir Linked to Potentially Fatal Skin Reaction, Robert Lowes, Retrieved April 19, 2013, WebMD, LLC, 2013.

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a611038.html, Telaprevir, Retrieved April 19, 2013, AHFS Consumer Medication Information, 2013.

http://www.rxlist.com/incivek-drug.htm, Incivek (telaprevir), Retrieved April 19, 2013, RxList, Inc., 2013.