Article | 24 January 2012
In an early benefit assessment pursuant to Germany’s Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG), has examined whether Incivo (telaprevir) offers an added benefit compared with the present standard therapy.
According to the findings of the assessment, telaprevir offers advantages in various groups of patients with chronic hepatitis C infection of genotype 1. The available studies provide proof, indications or "hints” of an added benefit. However, not only the probability but also the extent of added benefit varies, said the IQWiG.
The European Commission has approved Johnson & Johnson (NYSE: JNJ) subsidiary Janssen’s Incivo, a direct acting antiviral (DAA) protease inhibitor, for the treatment of genotype-1 chronic hepatitis C virus (HCV), in combination with peginterferon alfa and ribavirin, in adults (The Pharma Letter September 21, 2011). The drug was developed in collaboration with the USA’s Vertex and Japan’s Mitsubishi Tanabe and is approved and marketed under the trade name Incivek in the USA and Canada (TPLs May 24 and August 23).
In accordance with the approval status, different patient groups are treated for different periods, which was allowed for in the assessment. The dual combination of peginterferon alfa and ribavirin is the present standard therapy, and this was compared with the triple combination of these two standard drugs and telaprevir.
Studies largely only provide data on morbidity and adverse effects
Overall three relevant studies were identified. The outcomes considered were "mortality,” "secondary complications of treatment (morbidity)” measured in the studies by means of the surrogate outcome "SVR,” as well as "health-related quality of life” and "adverse effects.”
The quality-of-life results for treatment-naive (ie, previously untreated) patients without cirrhosis were not statistically significant. No evaluable data on this outcome were available for other patient groups. Due to the too short study duration, the event rates for mortality were too low in all patient groups to be able to draw robust conclusions.
Extent of added benefit cannot be classified on the basis of the surrogate outcome for morbidity
The extent of added benefit cannot be classified on the basis of the surrogate outcome "SVR,” the agency noted. This parameter is not a patient-relevant outcome in itself and there are no studies in which SVR is validated as a surrogate outcome in accordance with the usual criteria employed by IQWiG. Nevertheless, the Institute accepts SVR in the context of this assessment as a surrogate for the reduced incidence of liver cancer. This is because it is currently accepted that patients with no detectable hepatitis C virus in the blood are at lower risk of liver cancer. However, it is not known how many cases of liver cancer can in fact be prevented by telaprevir and it is therefore unclear whether the added benefit can be classified as "minor” "considerable” or "major.” According to the corresponding legal ordinance, the added benefit is thus "unquantifiable.”.Under consideration of the beneficial and harmful effects of telaprevir, overall IQWiG reaches different conclusions for different patient groups.
Advantages for treatment-naive patients without cirrhosis who have a high viral load
Different results for morbidity were shown for treatment-naive patients without cirrhosis, depending on the viral load in the blood at the start of treatment. Proof of an added benefit of telaprevir was only determined for patients with a high viral load. However, the extent of the added benefit is unquantifiable as it refers to the surrogate outcome "SVR.”
For treatment-naive patients without cirrhosis, the data also provide proof and an indication of greater harm due to the adverse effects anaemia and rash, respectively, the extent being classified as "considerable” in the former and "minor” in the latter case. In the consideration of the beneficial and harmful effects of telaprevir, this did not lead to a restriction in the overall conclusion for patients with a high viral load, as these side effects were nearly exclusively classified as "not serious,” said the IQWiG.
In contrast, for treatment-naive patients without cirrhosis who have a low viral load at baseline, the data provide an indication of lesser benefit of telaprevir versus the comparator therapy. This is due to the fact that an added benefit regarding SVR is not proven, so that only the harmful effects are taken into account. An added benefit of telaprevir is not proven for treatment-naive patients with cirrhosis, as the manufacturer dossier did not contain any evaluable data.
Indication of an advantage also in patients with unsuccessful pre-treatment
Depending on the cirrhosis status, different results were shown for patients in whom treatment had so far been unsuccessful (non-responders). Regarding morbidity, the data provide an indication of an added benefit of telaprevir in patients without cirrhosis. The data only provide a "hint” of an added benefit in non-responders with cirrhosis. In this context, "indication” and "hint” refer to the surrogate outcome "SVR.” Therefore the extent of added benefit is unquantifiable. As in the case of treatment-naive patients without cirrhosis, indications of greater harm due to the side effects "anaemia” and "rash” did not lead to a restriction in the overall conclusion.
No additional benefit for relapsed patients
In patients without cirrhosis who relapsed after standard therapy, the treatment regimen deviated from the approval status. Consequently, the added benefit cannot be assessed on the basis of the available data so that an added benefit is not proven, noted the IQWiG.
In patients with cirrhosis who relapsed, the data provide an indication of an added benefit regarding SVR. However, at the same time they also provide an indication of greater harm (extent: considerable) regarding serious adverse events. Under consideration of the beneficial and harmful effects of telaprevir, the IQWiG concluded that overall an added benefit is not proven for this patient group.
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