DDW: Telaprevir Said to Benefit Hardest HCV Case

DDW: Telaprevir Said to Benefit Hardest HCV Case
MedPage Today
Published: May 08, 2010

Links to full slide/poster reports at EASL;
EASL: Telaprevir in Null-Responders & Non-Responders - (04/15/10)
EASL: VX-222 Vertex NNRTI Polymerase Inhibitor 3 Days Monotherapy - (04/15/10)
EASL: Discrepancies Between Definitions of Null Response to Treatment with Peginterferon Alfa-2a and Ribavirin: Implications for New HCV Drug Development - (04/18/10)
EASL: On-Treatment Response-Guided Therapy with Telaprevir q8h or q12h Combined with Peginterferon Alfa-2a or Alfa-2b and Ribavirin in Treatment-Naïve Genotype 1 Hepatitis C (Study C208) - (04/18/10)
EASL: Activity of Telaprevir Alone or in Combination with Peginterferon Alfa-2a and Ribavirin in Treatment-naïve, Genotype 2 and 3, Hepatitis C Patients: Final Results of Study C209 - (04/18/10)

Action Points

* Explain to interested patients that telaprevir is not FDA approved for any purpose and is available only in a clinical trial setting.

* Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

NEW ORLEANS -- Adding an investigational protease inhibitor for hepatitis C virus (HCV) to standard treatment induced rapid and sustained virologic responses in many patients with poor responses to standard therapy alone, researchers said here.

In an open-label extension study, most patients with inadequate or no responses, or who showed renewed viral activity after an initial response to pegylated interferon and ribavirin, succeeded in achieving so-called sustained virologic responses to a second course of treatment that included telaprevir, reported Andrew Muir, MD, of Duke University.

Another analysis of one of these trials also showed that, among patients with inadequate initial responses to the standard regimen, even those with risk factors predicting especially poor responses did well when telaprevir was added, Muir said.

He presented the findings in two sessions here at Digestive Disease Week and at a press conference.

Telaprevir is one of two HCV protease inhibitors now in development, the other being boceprevir. These drugs are widely expected to be the first direct antiviral drugs made available for HCV, with FDA approval possible in 2011.

One of the studies Muir presented involved 117 participants in three earlier trials in the PROVE series who were in the standard-therapy arms and failed to show sustained virologic responses. They were categorized by the type of poor response: null responders (those with little or no change in viral loads), partial responders (initial decrease of at least two logs in HCV RNA but virus still detectable at week 24), and relapses and breakthroughs.

These patients underwent a second round of treatment with PEG-interferon and ribavirin at standard doses with the addition of telaprevir at 750 mg every eight hours. All three drugs were given for 12 weeks, with interferon and ribavirin continued for an additional 12 weeks.

Patients not showing complete responses at week 24 received an additional 24 weeks of interferon and ribavirin.

Muir said more than half of patients, 59%, had sustained virologic responses to the 12 weeks of telaprevir and 24 weeks of standard therapy.

Among the 35 who ended up taking interferon and ribavirin for the full 48 weeks, 52% had sustained responses.

The shorter regimen was not very effective in the subgroup with null responses to standard therapy during the PROVE studies. Only 13% of these patients developed sustained virologic responses during the first 24 weeks. But 57% of those who stayed on therapy for 48 weeks achieved sustained responses, according to Muir.

Among the other subgroups, response rates to the 24-week regimen ranged from 60% to 92%. Only seven patients in those subgroups received 48 weeks of treatment, of whom two obtained sustained responses.

The other study presented by Muir was a post hoc subgroup analysis of responses in "difficult to cure" patients in one of the earlier trials, PROVE3. These were patients who had one or more risk factors previously known to predict poor responses to interferon and ribavirin.

These included:

* HCV genotype 1
* Age
* High baseline viral load
* Male gender
* Obesity
* Bridging fibrosis in the liver

Participants in PROVE3 had all received prior unsuccessful treatment for HCV, so it was not surprising that, of the 342 patients included in the analysis, most had at least one of these risk factors.

PROVE3 was a randomized trial that assigned patients to interferon and ribavirin at standard doses for 48 weeks with or without 12 weeks of telaprevir, or to 24 weeks of the standard therapy plus 12 weeks of telaprevir. There was also a fourth arm, combining telaprevir and interferon without ribavirin, that was excluded from the new analysis.

Muir reported that, in each major risk-factor group, patients in both telaprevir arms did far better than those receiving the standard therapy alone.

Sustained viral responses were achieved in 44% to 61% of patients receiving telaprevir, compared with 10% to 15% of those receiving only the standard regimen (P<0.0001 for all comparisons), for the following subgroups: males, those older than 50, those with body mass index values of 25 to 30, those with BMI over 30, those with initial viral loads of more than 800,000 IU/mL, and those with bridging fibrosis or cirrhosis.

Patients with the risk factor associated with the worst outcomes -- those with no response at all to initial interferon and ribavirin treatment -- also did better with telaprevir, with 38% obtaining sustained responses.

Multivariate analysis indicated that adding telaprevir increased the chances of achieving a sustained response by nearly nine-fold (odds ratio 8.7, 95% CI 4.6 to 16.7).

In his presentations here, Muir spent little time addressing adverse effects. However, earlier reports from the PROVE series indicated that anemia and skin rashes and pruritus were relatively common with telaprevir.

Philip Schoenfeld, MD, of the University of Michigan in Ann Arbor, who moderated the press conference where Muir spoke, said the results with HCV protease inhibitors have been highly encouraging.

"These agents offer the opportunity for a revolution in the treatment of hepatitis C virus patients, achieving successful eradication of the virus in substantially more patients," he said.

In particular, Schoenfeld added, boceprevir and telaprevir offer "new hope for patients who have failed conventional therapies."