IQWiG Completes Early Benefit Assessment of Yervoy, Benlysta, and Fampyra

Germany's Institute for Quality and Efficiency in Health Care (IQWiG) on 2 May published early benefit assessment results for Bristol-Myers Squibb (US)'s Yervoy (ipilimumab), UK pharma GlaxoSmithKline (GSK)'s Benlysta (belimumab) and Swiss company Biogen Idec's Fampyra (fampridine). In the preliminary review, IQWiG found evidence of significant added benefit for Yervoy in the treatment of advanced melanoma, but concluded that lupus drug Benlysta and multiple sclerosis drug Fampyra brings no added benefit in their respective indication.

Yervoy: Significant Additional Benefit in Advanced Melanoma

IQWiG found evidence of significant additional benefit with Yervoy in the treatment of advanced skin cancer. The Institute based its early benefit assessment on one clinical trial that compared Yervoy plus best supportive care with best supportive care alone, the appropriate comparator selected by the Federal Joint Committee (G-BA). In the trial, patients were randomised in a 3:1:1 ratio to receive ipilimumab plus an investigational gp100 peptide vaccine (gp100), ipilimumab monotherapy, or gp100 alone. In addition, all patients received best supportive care. The ipilimumab-containing regimens demonstrated a statistically significant advantage in terms of overall survival, with a median overall survival of 10 months and 10.1 months in the ipilimumab/gp100 arm and in the ipilimumab monotherapy arm, respectively (versus 6.4 months in the gp100 control group). According to IQWiG, the extension of life is an indication of a significant additional benefit of ipilimumab plus best supportive care versus best supportive care alone. But the extent of serious side effects negatively impacts the incremental benefit score of Yervoy, for which there is evidence of a significant loss when it comes to serious side effects. The weight of benefit and damage pushed IQWiG to grant a significant added benefit score to Yervoy. Preliminary results of the early benefit assessment are available here.

Benlysta: No Added Benefit in Lupus

In parallel, IQWiG issued its conclusions on GlaxoSmithKline's Benlysta, estimating that the drug brings no added benefit in the treatment of systemic lupus erythematosus (SLE). The verdict is due to the fact that GSK provided no relevant study to assess the benefit of Benlysta versus "optimised standard therapy", the appropriate comparator selected by the G-BA. IQWiG justified its decision by saying that the design of the two pivotal studies (BLISS52 and BLISS76) contained in the manufacturer's value dossier was suitable for marketing authorisation application, but not for an early benefit assessment of the drug. Besides, the Institute added that the clinical study LBSL02, which was excluded from the value dossier, would have been suitable to compare Benlysta versus the appropriate comparator selected by the G-BA. IQWiG's preliminary verdict is available here.

Fampyra: No Added Benefit in MS

IQWiG issued a similar verdict for Fampyra but on different grounds. In its value dossier, Biogen Idec indirectly compared Fampyra to physiotherapy treatment—the appropriate comparator selected by the G-BA—as no direct comparative data was available. In Germany, the use of indirect comparisons is accepted if there are no direct comparable studies for a new active ingredient compared to the appropriate comparator. But the indirect comparison performed by the manufacturer did not fulfil methodological requirements according to IQWiG. As such, IQWiG concludes that clinical data provided by the manufacturer were not receivable to provide evidence of an additional benefit with Fampyra. IQWiG's review is available here.

Outlook and Implications

The G-BA will issue a final verdict on the added benefit profile of Fampyra, Benlysta, and Yervoy at the beginning of August 2012. The G-BA is set to issue verdicts in line with conclusions drawn by IQWiG, even though divergences are not excluded in light of the recent decisions made by Germany's supreme decision-making body. The G-BA has taken divergent views for a number of products so far, including for breast cancer drug Halaven (eribulin; see Germany: 27 April 2012: German Regulator Acknowledges Halaven's Benefits for Breast Cancer), hepatitis C treatments Victrelis (boceprevir; Merck & Co, US; see Germany: 5 March 2012: G-BA Comes to Different Conclusion Than IQWiG on Victrelis) and Incivo (telaprevir; Janssen-Cilag, US), and prostate cancer drug Jevtana (cabazitaxel; Sanofi, France; see Germany: 10 April 2012: G-BA Makes Final Conclusions on Five New Medicines). The Committee has overall been more generous than IQWiG for these products, except for Jevtana which obtained a lower than expected innovation score from the G-BA.