Tag Archives: telaprevir

New Hepatitis C Drug Approved: Janssen’s Hepatitis C Drug Simeprevir Now Available

This past week, the FDA gave approval to Janssen’s new drug to treat hepatitis C. Simeprevir, commercially know as OLYSIO, is the first new hepatitis C drug since the release of telapravir (Incevik) and boceprevir (Victrelis) in 2011. Simeprevir is a  NS3/4A protease inhibitor, used in combination with interferon and ribavirin.

The release of simeprevir marks the beginning of a new wave of direct acting antiviral agents against the hepatitis C virus. Additional drugs are set for FDA approval, including the Gilead drug sofosbuvir in early December 2013.

Most of the new hepatitis C drugs will have a number of features in common. These include:

  • Very high cure rate, in the 80-90% range – lower in null and non-responders
  • Less side effects
  • Shorter duration of treatment
  • Less pills to take each day
  • Cirrhosis reduces response rates
  • Less drug-drug interactions
  • Genotype 1 subtype differences exist

Looking at the dosing of simeprevir, I have attached the official product insert that describes how the drug will be doses. Several points to consider:

  • This is an interferon/ribavirin based therapy
  • Patients with genotype 1 need additional screening for the NS3 Q80K polymorphism
  • Those with this variant have a decreased response rate to the therapy, and should be considered for an alternative therapy
  • The initial dosing is 12 weeks of simeprevir with interferon and ribavirin, followed by an additional 12 or 36 weeks of interferon and ribavirin combination therapy.
  • There are drug-drug interaction which have to be monitored closely
  • FDA approval is for genotype 1 patients only

While the release of simeprevir is welcomed, it has not provided the proverbial “home-run” we have been looking for in our quest to cure hepatitis C. In well selected patients, achieving a better than 80% cure rate is available. The concerns I have relate to the Q80K polymorphism noted above. This will be an additional step required in screening our patients. Additionally, in patients with prior non-response or null responders, as well as those with cirrhosis, these patients will still require a full 48 week of interferon and ribavirin. One of the goals of the next generation of hepatitis C therapies is reduced interferon exposure, or complete elimination. Simeprevir does not fully meet this goal.

In the days to come, I will post additional information on sofosbuvir. For now, these are the highlights to consider (refer to this FDA document for additional details):

  • Sofosbuvir will likely receive FDA approval for Genotype 1,2,3, and 4 patients with hepatitis C
  • Interferon-free treatment in genotype 2 and 3 for 12 weeks
  • Sofosbuvir combined with interferon and ribavirin in genotype 1 and 4 for 12 to 16 weeks

This treatment strategy is far different than the simeprevir treatment noted above.

Looking further, we will eventually have all interferon-free protocols. It is anticipated that as additional new drugs are approved, they will be combined (example sofosbuvir and simeprevir), allowing us to treat a wide range of patients, safely, and with a cure rate many of us may have never envisioned 20 years ago.

For a consultation to see if you are a candidate for these new drugs, contact Lexa at our office at 713-794-0700 and visit our webpage for additional information.

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Starting New FDA Approved Hepatitis C Therapies: What Patients Need to Know

This week, we will be starting therapy using the new FDA approved protease inhibitors, Victrelis (boceprevir) and Incivek (telaprevir) in our patients with chronic hepatitis C.

Below is a brief podcast explaining some of the procedures required prior to initiating therapy with these new agents.

Listen to the podcast here: Hepatitis C Treatment Introduction

Call our office at 713-794-0700 if you have questions.

Liver Specialists of Texas
6624 Fannin, Suite 1990
Houston, TX 77030

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Telaprevir and FDA Approval: The Race is On for New Hepatitis C Drugs

Telaprevir and FDA Approval: The Race is On for New Hepatitis C Drugs

Liver Specislists of Texas-HCV Research

For those of us that are involved in the care of patients with chronic hepatitis C, the “never too soon” announcement that we will finally have new drugs to treat our hepatitis C patients with cannot come soon enough. There is a real possibility that one and possibly two new agents for hepatitis C will be granted approval by the FDA in the months to come. When that day will be is unknown to me, but I anticipate later this summer at the latest.

There is a frenzy of discussion in the press, as well as the blogosphere on the new drugs, namely Telaprevir, manufactured by Vertex, and Boceprevir, manufactured by Merck. I have had the opportunity to use both of these drugs in clinical studies over the past several years, and understand how they both work, and what patients can expect. Much to everyone’s surprise, patients will still need to take one of the pegylated interferons once weekly, and ribavirin twice daily. The new drugs are added to this backbone of therapy. Besides the expected interferon and ribavirin side effects, the protease inhibitors do add some additional problems, but for the most part, in experienced hands, they can be managed fine. Once these drugs are approved, I anticipate a mad-dash of patients, wanting to get their hands on these therapies.

My advise is to start requesting your old records now if you were previously treated. Knowing exactly how many weeks you were treated, what your response was, and what complications developed, will be important information prior to commencing any sort of new therapy, regardless of which protease inhibitor you are started on. It can take weeks to get these records, so start asking now.

There are hundreds of thousands of patients with hepatitis C that are either naive to therapy (never treated), or previously treated with a partial response (null responder, non-responder, or responder-relapser). All of these individuals should be considered for these new therapies, but you need to be sure you are being seen by a practice that can handle these patients. With the new protease inhibitor drugs, resistance can become an issue, and discontinuing the therapy in a timely fashion is important. The treatment protocols are different from prior therapies, with a lead-in phase with interferon. All of these steps requires careful monitoring and communication with the patient. An experienced staff of nurses will be needed. Prior to being evaluated for these new exciting drugs, you, as a consumer, need to ask these questions to see if your care provider has the necessary experience, as well as a dedicated team to support them once patients are started on therapy.

Besides the two contenders for FDA approval later this summer, the pipeline for additional drugs is incredibly long. We are conducting research studies on an additional 12 drugs, all of which look promising. Some of the protocols are free of the hated interferon. Imagine, HCV therapy without interferon? That day will be here, allbeit several more years. I am currently in Chicago with the HCV team from Abbott, who also has a number of exciting compounds we will start studying soon with our patients in Houston.

So, when will the new hepatitis C drugs be available? My best educated guess will be by Labor Day, but we may all be surprised sooner, based on the chatter in the press and FDA hallways.

I am eager to hear what you think? Comment on your prior experience with hepatitis C therapy.

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Telaprevir Continues to Show Promise for Hepatitis C Patients

Telaprevir Continues to Show Promise for Hepatitis C Patients

New Therapies Soon

In a recent report, there are continued signs that Telaprevir in combination with Interferon and Ribavirin will have significantly increased rates of clearing the hepatitis C virus. New agents against hepatitis C are due for FDA approval in the second half of 2011. For the past three years, we have been fortunate at Liver Specialists of Texas to have been participating in these clinical studies, and remain active with over 15 ongoing hepatitis C research studies. If you are interested in research opportunities, call us 713-794-0700.  The full article is posted below.

In patients with chronic hepatitis C, combining telaprevir with ribavirin and peginterferon alfa-2a or 2b yielded sustained virologic response rates of more than 80%, regardless of which type of interferon or which dosing regimen of telaprevir was used, Dr. Patrick Marcellin and his colleagues reported in the February issue of Gastroenterology.

The researchers assessed the efficacy and safety of four different dosing approaches in a phase II, open-label clinical trial, which they described as “the first trial comparing the two licensed peginterferon alfa/ribavirin treatments in combination with the same protease inhibitor.” The study was conducted at 30 medical centers in Austria, Belgium, France, Germany, Italy, Spain, and the Netherlands, and included treatment-naive patients aged 18-65 years who had no cirrhosis, history of drug use, HIV coinfection, or any suspicion of alcohol use (Gastroenterology 2011;140:459-468.e1).

The 161 study subjects were randomly assigned to four treatment groups: 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2a and ribavirin; 750 mg of telaprevir taken every 8 hours plus peginterferon alfa-2b and ribavirin; 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2a and ribavirin; or 1,125 mg of telaprevir taken every 12 hours plus peginterferon alfa-2b and ribavirin, said Dr. Marcellin of Beaujon Hospital, University of Paris, Clichy, France, and his associates.

Subjects who had undetectable plasma levels of hepatitis C virus (HCV) RNA at weeks 4-20 (109 patients) were scheduled to discontinue treatment at 24 weeks, while those who still had detectable HCV RNA (29 patients) were scheduled to continue for the standard 48 weeks of treatment. A total of 33 patients dropped out of the study before completing their assigned treatment.

The main efficacy end point was the percentage of patients who achieved a sustained virologic response, with levels of HCV RNA that were either undetectable or less than 25 IU/mL.

Overall, this percentage was not significantly different among the four treatment groups: 85% in group 1, 81% in group 2, 83% in group 3, and 82% in group 4.

Given the small number of patients in each treatment arm of this trial, different dosing regimens warrant further study in a larger clinical trial, the authors added.

This primary outcome also was not significantly different when the results were pooled for all patients taking telaprevir every 8 hours (83%) compared with all patients taking telaprevir every 12 hours (82%), as well as when the results were pooled for all patients taking peginterferon alfa-2a (84%) compared with all patients taking peginterferon alfa-2b (82%).

When the results were assessed according to duration of treatment, 96% of the patients who were treated for only 24 weeks achieved a sustained virologic response, as did 79% of those who received the standard 48-week course. This strategy of guiding treatment duration according to each patient’s virologic response at 4-20 weeks was clearly successful, allowing the majority of patients to cut their course of treatment by half without adversely affecting efficacy.

“This response-guided treatment duration strategy is currently being further explored in ongoing telaprevir phase III clinical trials in treatment-naive patients,” Dr. Marcellin and his colleagues noted.

When the results were assessed according to completion of assigned treatment, 95% of the 128 patients who completed treatment achieved a sustained virologic response.

Both the every-8-hours and every-12-hours doses of telaprevir were equally effective at producing a sustained virologic response, and were equally tolerated by patients. There also were no significant differences between the two doses in relapse rates or in safety profiles. “Thus, it could be hypothesized that coadministration of telaprevir with standard therapy might allow for less frequent telaprevir dosing,” the investigators said.

Similarly, both formulations of peginterferon were equally effective in this study, although the two agents have different pharmacokinetic properties and a recent meta-analysis suggested that peginterferon alfa-2a is slightly more effective.

This clinical trial was funded by Tibotec, a division of Janssen-Cilag, and by Vertex Pharmaceuticals. The authors reported ties to 18 pharmaceutical and biomedical technology companies.

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