By: Ramya Mathew, PharmD Candidate c/o 2015
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Vertex Pharmaceuticals, an American biotechnology company based in Cambridge, Massachusetts, has been researching a new “nuke” for the treatment of Hepatitis C called VX-135. This nucleotide polymerase inhibitor is currently undergoing clinical trials, but the FDA has put the research on a partial hold due to findings of possible liver toxicity. The partial hold was initiated after the adverse effect was seen in Europe, where VX-135 is approved. Patients involved in a post-marketing study had elevated liver enzymes levels. Three out of ten patients who were on a 400-mg dose of VX-135 had this liver toxicity, and the problem resolved once the medication was discontinued.1 The partial hold only concerns the 200-mg dose of the medicine; however, the 100-mg dose regimen, which remains unaffected by this hold, is also under study.
Hepatitis C virus (HCV) causes infection that leads to inflammation of the liver. The infection commonly goes unnoticed due to the initial asymptomatic stage. Because of this, patients may go untreated for years until the virus causes serious liver damage, found during routine medical checkups.2 Current treatment regimens for HCV involve using drugs such as pegylated interferons, which is administered subcutaneously and can have serious side effects. The new drug is expected to be a game-changer in hepatitis C management but has been plagued by safety concerns.
Vertex Pharmaceuticals is not the first to have the FDA intervene on their clinical trials. Finding treatments for HCV has become a multibillion-dollar market and several drug companies, including Bristol-Meyers Squibb and Idenix Pharmaceuticals, have also had their clinical trials for similar medications stopped due to toxicity findings. BioCryst Pharmaceuticals also dropped their “nuke,” BCX5191, in October 2012 due to an unfavorable safety profile.1
But the FDA has not halted all “nuke” trials. As of June 2013, it is likely that both Simeprevir and Sofosbuvir will receive FDA approval in 2014 for anti-HCV treatment. Both are currently in their Phase III clinical trials and show promising results. Simeprevir, developed by Janssen Pharmaceuticals, showed continued virologic response for 12 weeks post-treatment in 79% of treatment-experienced adults who have genotype 1 chronic hepatitis C. Simeprevir is administered once daily with pegylated interferon and ribavirin.3 Sofosbuvir, developed by Gilead Sciences, has shown a 90% sustained virologic response at 12 weeks when given with pegylated interferon and ribavirin in patients with geno-type 1 or 4 HCV infection.4
Finding new oral treatments, such as these nucleotide polymerase inhibitors, is the goal of many drug companies. They hope that the new treatments will be better tolerated and be more effective than the agents currently available. Although there are numerous HCV treatment compounds in the pipeline, only a few seem to have a chance in being approved and placed on the shelves in the US. For now, all we can say is that it might take a few years before drugs like VX-135 can show their potential to revolutionize the treatment of Hepatitis C.
SOURCES:
- Jones K. Vertex: FDA Puts Partial Hold on Study of Hepatitis C Drug. The Wall StreetJournal.http://online.wsj.com/article/BT-CO-20130725-718983.html?mod=googlenews_wsj. Accessed August 22, 2013.
- Hepatitis C. World Health Organization. Website. http://www.who.int/mediacentre/factsheets/fs164/en/. Updated July, 2013. Accessed October 20, 2013.
- Johnson J. Primary Efficacy and Safety Findings from Phase 3 Study of Janssen’s Simeprevir Administered Once Daily Demonstrate Sustained Virologic Response in Treatment-Experienced Genotype 1 Chronic Hepatitis C Adult Patient. Johnson & John-son. http://www.investor.jnj.com/releasedetail.cfm?ReleaseID=766263. May 21, 2013. Accessed August 22, 2013.
- Lawitz E, et. al. Sofosbuvir for Previously Un-treated Chronic Hepatitis C Infection. NEJM. http://www.nejm.org/doi/full/10.1056/NEJMoa1214853. Accessed August 23, 2013.
