The tale of lenalidomide clinical superiority over thalidomide and regulatory and cost-effectiveness issues

Abstract

In April 2017, the National Sanitary Surveillance Agency (ANVISA-Brazil) approved lenalidomide (LEN) for multiple myeloma (MM) and myelodysplastic syndrome. ANVISA had rejected the first application in 2010, and denied a request for reconsideration in 2012. The reason for rejection was the lack of comparative effectiveness studies proving that LEN was more effective than thalidomide (THAL), a strictly controlled drug regulated by Federal law 10.651/2003 and dispensed to patients (at no costs) through public health system units and hospitals. ANVISA unexplained retreat on the LEN approval for marketing was an unquestionable triumph of the lobbying that ensued the denial, at the forefront of which were politicians, Congress members, patient organizations and medical societies. Two randomized (phase III) trials and three observational (case-control and population-based cohort) compared the effectiveness of THAL- versus LEN-based therapies in MM. Overall, these studies showed no difference in efficacy between LEN- and THAL-based therapies. LEN caused less neuropathy, and more severe hematologic adverse effects. It is much costlier than THAL, and substitution of THAL by LEN shall raise considerably public healthcare costs in Brazil.

Effect of Lenalidomide Ointment on TNF-α Tissue Levels in Mice with Imiquimod-Induced Psoriasis.

“…Lenalidomide is a thalidomide analogue that was synthesized by altering the chemical structure of thalidomide. On the other hand, it is significantly safer and more powerful than thalidomide, with fewer side effects and toxicities (9). Lenalidomide enhances host immunity in a variety of ways and supports the death of malignant cells (10).…”

Judicialização da saúde: análise dos processos judiciais do medicamento lenalidomida impetrados contra a Secretaria de Saúde do Estado de São Paulo para tratamento de mieloma múltiplo

“…Os pacientes com MM em tratamento com esquemas baseados no uso de lenalidomida permanecem em risco de TEV, apesar das estratégias atuais de tromboprofilaxia obrigatória (CHAKRABORTY et al, 2019) e a lenalidomida causa mielossupressão. (HOFFBRAND, 2018) Estudos analisaram a questão da lenalidomida ser taxada como clinicamente superior a talidomida (PAUMGARTTEN, 2019;TEODORO, 2017), concluindo que a substância não apresenta ser clinicamente superior na prática, principalmente analisando o custo-benefício da produção e fornecimento da talidomida no Brasil, ser de produção e gestão pública. Lima et al (2019) avaliou custo efetividade do tratamento de MM com lenalidomida na Espanha e concluiu que os altos valores de relação custo-utilidade incremental (ICUR) e impacto orçamentário, a relação benefício / risco / custo se mostrou duvidosa, principalmente nos pacientes com probabilidade alta de risco de recidiva.…”