Ibrutinib (Imbruvica®) for the treatment of adult patients with previously untreated chronic lymphatic leukaemia (CLL)

Zorginstituut Nederland has completed its assessment whether ibrutinib (Imbruvica®) for the treatment of adult patients with previously untreated chronic lymphatic leukaemia (CLL) can be included in the insured package. Due to its expected high costs the Minister of Medical Care and Sports has placed ibrutinib in the so-called ‘package lock’ or ‘sluice’ for expensive drugs. These products can only be accepted into the insured package after the Zorginstituut has advised on their inclusion in the insured package and, where applicable, subject to Ministry negotiations to arrive at a financial arrangement with the supplier. The Zorginstituut advises the Minister to include ibrutinib in the insured package, after successful price negotiations on the basis of a realistic public price proposal from the manufacturer.

Criteria for including treatments in the insured package

The Zorginstituut assessed ibrutinib based on the four package criteria: effectiveness, cost-effectiveness, necessity and feasibility. Assessing from the perspective of the basic package which is paid from collective premiums, the Zorginstituut looks at whether new care is better than what is currently available. In doing this we look not only at the degree of certainty that has been achieved, from a scientific perspective and from the perspective of societal support, but also at efficiency aspects. The Zorginstituut was advised by two independent committees: the Scientific Advisory Board (WAR) which examines data on established medical science and medical practice and determines the cost-effectiveness, and the Insured Package Advisory Committee (ACP) which considers the societal assessment. Stakeholders are also consulted during the process.

Zorginstuut's advice

Ibrutinib has an orphan drug status. It has already been assessed (mid 2017) by the Zorginstituut, at the request of the Minister (as part of the ‘lock procedure’), for the indication of monotherapy in patients with previously untreated CLL, without a del17p or TP53 mutation. For patients with these mutations, ibrutinib was already included in the package as primary care treatment at that time.

Ibrutinib now meets the established medical science and medical practice for the entire group of adult patients with previously untreated CLL without del17p or TP53 mutation:

  • fit patients ≤ 65-70 years and an unmutated IGHV;
  • fit patients > 65-70 years;
  • unfit patients.

Treatment with ibrutinib provides a clinically relevant improvement in the progression-free survival of at least 6 months, compared to the standard treatment applied to the mentioned patients. It is still unclear whether ibrutinib will also lead to an improved survival compared to standard treatment. The undesirable effects of ibrutinib are acceptable. Compared to current therapies, ibrutinib has the advantage that it can be administered orally.

Ibrutinib has already been registered for several indications and is included in the basic insured package here in the Netherlands and in other countries. In any case, the investments made by the manufacturer have already been partially recovered. This justifies a lower price below the reference value. Because there is still uncertainty about the influence of ibrutinib on the overall survival and quality of life of patients with CLL, and because the registered indications of ibrutinib will be extended in the coming years, the price reduction should be more substantial than what is now mentioned in the pharmaco-economic report (25% to a maximum of 75%).

The Zorginstituut recommends the Minister to proceed to price negotiations and inclusion in the package and to invite the manufacturer to come up with a publicly available realistic price proposal.

This report is a summary of recommendations by Zorginstituut Nederland. The original text of this excerpt is in Dutch.