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New Data for Investigational Hepatitis C Drug Telaprevir (VX-950) to be Presented at AASLD Meeting
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- Combination therapy with telaprevir and pegylated interferon suppressed both wild-type and resistant HCV -
Reported by Vertex
Boston, MA, October 27, 2006 -- Researchers will present new data this week suggesting that both wild-type hepatitis C virus and resistant variants were suppressed in patients when pegylated interferon (peginterferon alfa-2a; peg-IFN) was added to telaprevir (VX-950), Vertex's investigational hepatitis C virus (HCV) protease inhibitor, in a Phase 1b clinical study. In addition, clinical investigators will report that 24 of 26 patients who received telaprevir (VX-950) in two early-stage clinical trials had undetectable HCV RNA after receiving follow-on combination therapy with peg-IFN and ribavirin (RBV) through 24 weeks of treatment, a therapeutic regimen following the conclusion of the clinical trials. Clinical investigators will also report that some of these patients have stopped therapy, and that a proportion of them continued to have undetectable HCV RNA after stopping therapy.
The data will be presented while attending the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) and were released in accordance with media guidelines established by the conference. Telaprevir (VX-950) is an investigational drug candidate being developed as part of a global Phase 2b clinical development program by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX).
Combination of Telaprevir (VX-950) and Peg-IFN Suppressed Both Wild-type Virus and Resistance Variants in 14-day Clinical Study
Tara Kieffer, Ph.D., of Vertex will present data in a Presidential Plenary session on Monday, October 30, analyzing viral sequences isolated from patients receiving telaprevir (VX-950) as a single agent or in combination with peg-IFN in a Phase 1b 14-day clinical study. In this study, viral variants were suppressed when peg-IFN was combined with telaprevir, or when peg-IFN and RBV were administered subsequent to telaprevir dosing.
In one arm of the trial, resistant viral variants were isolated from six of eight patients who had detectable HCV RNA while receiving telaprevir as a single agent over a period of 14 days. Subsequently, clinical investigators reported that all patients who received follow-on therapy with peg-IFN and RBV had undetectable HCV RNA at 24 weeks. In a second arm of the study, resistant viral variants were isolated from two of eight patients who received a combination of telaprevir and peg-IFN for 14 days. Both patients subsequently had undetectable HCV RNA at week 12 of follow-on therapy.
Current Status of Patients Receiving Follow-On Peg-IFN and RBV Combination Therapy After a 14-day, Phase 1b Clinical Trial of Telaprevir (VX-950)
On Tuesday, October 31, Dr. Nicole Forestier of Saarland University Hospital in Homburg, Germany will review the current status of 20 patients from a Phase 1b study who received 14 days of telaprevir therapy either alone or in combination with peg-IFN, or peg-IFN alone, in a poster presentation titled "Current status of subjects receiving peg-interferon alfa-2a (peg-IFN) and ribavirin (RBV) after a 14-day study of the hepatitis C protease inhibitor telaprevir (VX-950), with peg-IFN." Clinical investigators previously reported that at the end of 14 days of dosing, one of eight patients receiving telaprevir as a single agent and four of eight patients receiving telaprevir in combination with peg-IFN had undetectable HCV RNA (less than 10 IU/mL, Roche Taqman®).
All patients who did not discontinue therapy at week 24 are expected to continue to receive peg-IFN+RBV for a total of 48 weeks of treatment. The current status of patients, as reported by the poster authors, is described in the following table:
HCV RNA Results for patients receiving follow-on peg-IFN+RBV therapy following 14-day Phase 1b study of telaprevir (VX-950)
*one patient in the VX-950 alone group refused follow-on therapy after the initial 14-day dosing period.
**at the 24 week timepoint, 4 of the 7 patients originally randomized to the VX950 monotherapy arm, and 6 of the 8 originally randomized to VX950+peg-IFN arm, were determined to be eligible by their physicians to stop treatment at week 24, and following discussions, were willing to stop treatment at that timepoint in order to assess whether they would maintain undetectable HCV RNA status. Two of the 4 patients from the VX950 monotherapy arm, and 1 of the 6 patients from the VX950+peg-IFN arm, had undetectable HCV RNA within 12 weeks after stopping therapy.
Current Status of Patients Receiving Follow-On Peg-IFN and RBV Combination Therapy After a 28-day, Phase 2a Clinical Trial of Telaprevir (VX-950)
On Monday, October 30, Dr. Maribel Rodriguez-Torres of Fundacion de Investigacion de Diego, Puerto Rico will review the current status of 12 patients originally enrolled in a 28-day Phase 2a study of telaprevir in a poster presentation titled "Current status of subjects receiving peg-interferon alfa-2a (peg-IFN) and ribavirin (RBV) follow-on therapy after 28-day treatment of the hepatitis C protease inhibitor telaprevir (VX-950), peg-IFN and RBV." Clinical investigators previously reported that at the end of 28 days of dosing with telaprevir in combination with peg-IFN and RBV, 12 of 12 patients had HCV RNA below the limit of detection of a highly sensitive assay (less than 10 IU/mL, Roche Taqman®).
The current status of patients, as reported by the poster authors, is described in the following table:
At the end of 24 weeks of follow-on peg-IFN+RBV therapy, eight patients who were still receiving peg-IFN+RBV had undetectable HCV RNA. These patients continue to receive peg-IFN+RBV at week 36 of follow-on therapy. Additionally, one patient stopped treatment at week 18 and remained HCV RNA undetectable 6 weeks after stopping therapy (week 24).
Two patients had detectable HCV RNA and stopped treatment at week 24 of follow-on therapy. In these two patients, viral sequencing analyses at week 24 showed predominantly wild-type virus, with a minority population of R155K variants also detected. One patient, after having undetectable HCV RNA at week 12, was lost to follow-up at week 18 of follow-on therapy.
The results reported above represent clinical treatment of comparatively small numbers of patients who were initially dosed in clinical trials of telaprevir for 14 or 28 days. These results may not be predictive of patient outcomes in large clinical trials evaluating telaprevir.
In clinical studies reported to date, telaprevir has been administered as a single agent, in combination with peg-IFN only, and in combination with peg-IFN and RBV for 28 days or less. In subjects who received telaprevir alone, commonly reported adverse events were headache, diarrhea, urinary frequency, sleepiness, and skin disorders (dry skin, rash and itching). In subjects who received telaprevir in combination with peg-IFN and with or without RBV, the commonly reported adverse events were flu-like symptoms, fatigue, headache, nausea, anemia, depression, insomnia, and skin disorders (dry skin, rash and itching). Except for one headache in one patient receiving telaprevir in combination with peg-IFN and RBV that was judged to be severe, adverse events across all studies reported to date were mild to moderate.
Two additional presentations involving telaprevir will be presented at AASLD:
* Chao Lin, Ph.D., of Vertex will present in vitro analyses on Sunday, October 29. In Dr. Lin's study, variants with decreased sensitivity to telaprevir remained sensitive to interferon alpha and ribavirin.
* Raj Kalkeri, Ph.D., of Vertex will present in vitro data on Monday, October 30. In Dr. Kalkeri's study, HCV protease variants with decreased sensitivity to telaprevir were less efficient in cleaving proteins involved in innate immunity.
About Telaprevir (VX-950)
Telaprevir (VX-950) is an investigational oral inhibitor of HCV protease, an enzyme essential for viral replication, and is one of the most advanced investigational agents in development that specifically targets HCV. Vertex is conducting a global Phase 2b clinical development program for telaprevir consisting of three large clinical trials that are expected to enroll approximately 1000 patients with HCV at clinical centers in the United States and Europe. Vertex completed enrollment in the 260-patient, U.S.-based PROVE 1 trial in September. The PROVE 2 trial is underway in Europe and is expected to complete enrollment by year-end with approximately 320 patients. Also in the fourth quarter, Vertex expects to initiate PROVE 3, a clinical trial of telaprevir that will enroll more than 400 treatment-experienced patients. In clinical trials, telaprevir is being dosed as 750 mg every eight hours in combination with pegylated interferon alfa-2a (Pegasys®), both with and without ribavirin (Copegus®).
Vertex retains commercial rights to telaprevir in North America. Vertex and Tibotec are collaborating to develop and commercialize telaprevir in Europe, South America, Australia, the Middle East, and other countries. Vertex is collaborating with Mitsubishi Pharma to develop and commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by infection with hepatitis C virus (HCV), which is found in the blood of people with the disease. HCV, a serious public health concern affecting 170 million people worldwide, is spread through direct contact with the blood of an infected person. Though many people with hepatitis C may not experience symptoms, others may have symptoms such as jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and early death.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, inflammation, autoimmune diseases, cancer, pain and bacterial infection. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
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