NICE Rejects MabThera Maintenance Therapy and Lucentis in DMO

NICE Reverses Earlier Positive Recommendation for MabThera

The United Kingdom's National Institute for Health and Clinical Excellence (NICE) has issued a second appraisal consultation document (ACD) outlining that Swiss pharma major Roche's MabThera/Rituxan (rituximab) is not recommended as a first-line maintenance treatment for people with advanced follicular non-Hodgkin's lymphoma (NHL) that has responded to first-line induction therapy with MabThera in combination with chemotherapy. The manufacturer's economic analysis consisted of a systematic literature review to identify studies addressing quality of life, and an economic model of various health states that incorporated drug acquisition and administration costs, as well as costs of supportive care, management of adverse events, and monitoring. The model produced a base-case incremental cost-effectiveness ratio (ICER) of GBP15,978 (USD25,054) per quality-adjusted life year (QALY) gained for MabThera maintenance treatment compared with observation. According to the sensitivity analyses, the model was sensitive to the duration of treatment effect and assumptions around supportive care and administration costs. When it was assumed that the effectiveness of the treatment stopped after 47 months, as apposed to 72 months in the base-case analysis, the ICER was GBP21,151 per QALY gained. When it was assumed that the clinical benefit lasted only for 26 months, the ICER more than doubled to GBP32,230 per QALY gained. Following a request for additional data after the first appraisal consultation, the manufacturer conducted further analysis of the effect on the ICER of difference assumptions about progression-free survival (PFS) translating into overall survival (OS), the clinical benefit from MabThera being either three or four years, and the age of a patient at induction being between 60 and 65 years. In the revised analysis, the majority of ICERs for MabThera maintenance therapy compared with observation were less than GBP30,000 per QALY gained. However, when it was assumed that patient age at induction was between 60 and 65 years, treatment conferred benefits for three years, and the conversation rate from PFS to OS was 50%, the ICER for MabThera exceeded GBP36,000 per QALY gained. NICE also noted that the prior preliminary decision to recommend MabThera maintenance treatment had been criticised by some of the consultees due to uncertainties about the clinical benefit of the drug in terms of survival and quality of life. Consultees were also critical of the economic model, as some of the assumptions were not deemed to be plausible, and as such, there is much uncertainty surrounding the estimates. NICE was therefore minded to reverse its earlier recommendation, and concluded that MabThera is not cost-effective in the maintenance setting. The ACD is available here.

Lucentis Also Rejected

In another ACD, NICE has also rejected Lucentis (ranibizumab; Novartis, Switzerland) for the treatment of visual impairment due to diabetic macular oedema (DMO). According to NICE, the economic analysis provided by the manufacturer does not adequately reflect current clinical practice for the treatment of DMO, as it did not account for the need to treat both eyes in a significant proportion of people with DMO. The analysis also overestimated the life expectancy of diabetes patients, while underestimating the quantities of the drug that patients with DMO would have to take to achieve the benefits assumed in the analysis. The ICERs for Lucentis monotherapy in comparison with laser photocoagulation exceeded GBP30,000 per QALY gained based on the base-case analysis. As most of the assumptions used in the analysis have been underestimated, NICE concluded that the most plausible ICER would most likely exceed the threshold for cost effectiveness. NICE's statement on the decision is available here.

Outlook and Implications

NICE's latest decision on MabThera maintenance therapy will come as a blow for Roche, after an earlier positive decision. However, NICE had indicated that the most plausible ICER for the drug remained in question, and requested further data for clarification. Its decision therefore reflects the new information provided. NICE has also requested additional cost-effectiveness analysis from the manufacturer, looking specifically at assumptions such as changing the age at first-line induction to 62.5 years, assuming the duration of clinical benefit from first-line maintenance treatment is 28 months, 36 months, or 48 months, and the extent that the benefit of mean PFS from treatment translates to mean OS gain is 70%, 80%, or 90%. MabThera is currently reimbursed as a maintenance therapy for the treatment of relapsed stage III or IV follicular NHL in remission, induced with chemotherapy with or without MabThera, based on an ICER of GBP13,000 per QALY. The average cost of maintenance treatment with MabThera is estimated to be GBP14,669—excluding value-added tax—over two years (see United Kingdom: 6 December 2010: NICE Recommends MabThera Maintenance Therapy, New Data Tout Benefits in Asymptomatic Follicular Lymphoma). The next appraisal consultation meeting is scheduled for 5 April.