Belgium Steps Further into Immunotherapies – Highlighting Open European Questions

From May onward, Belgian lung-cancer patients can receive – and be reimbursed for - immunotherapy for first-line treatment. This breakthrough, decreed by the Belgian health ministry, offers another possibility for assessing the efficacy of this still-controversial approach, which has so far won reimbursement status in only limited indications in most countries in Europe. Only Austria, Luxembourg, Denmark, Finland, Sweden and Germany have reimbursed immunotherapy for first-line treatment of lung cancer.

Maggie De Block, Belgium's Minister of Social Affairs and Public Health, didn't mince her words in making the announcement: "Patients will have access to therapy that increases their chances of survival and significantly improves their quality of life throughout treatment. This is important because they are seriously ill, often terminally ill."

Until now, Belgium has been making Bristol-Myers-Squibb's Opdivo (nivolumab) immunotherapy available only for some 500 patients with melanoma, Hodgkin's lymphoma, and renal cancer, and for second-line treatment of lung cancer. From May 1st, MSD's Keytruda (pembrolizumab) is available for first line treatment for lung cancer through infusion every three weeks in patients who have more than 50% of PD1 receptors on their tumor cells.

This means that during the course of 2017, a total of 5,000 patients may have access to immunotherapy in Belgium, the largest group being the 2,000 patients in first- and second-line treatment for lung cancer. And in 2018, the number of patients receiving immunotherapy is expected to increase to 9,000; rising again to as many as 11,000 patients in 2019.

De Block sees immunotherapy as evolving rapidly. She cites a 45% response rate among patients, compared with 28% responses rates to chemotherapy, together with much fewer side effects. "Over the next few months, I expect that more similar treatments will be reimbursed more quickly," she said, suggesting that cancers of the bladder and the neck could be covered.

The therapies will be fast-tracked through the country's accelerated reimbursement procedure. Since the beginning of this year, the reimbursement of immunotherapies follows a non-traditional path in Belgium. The expected cost of this accelerated repayment is in excess of $125 million per year, but has been provided for through recent government measures that create an additional envelope for innovative medicines. Within that new scheme, "price agreements have been concluded with the companies concerned," De Block adds – without going into any detail about what prices have been agreed upon.

The initiative, interesting in itself, also highlights some of the gaps in the European provision of novel therapies in general, and immunotherapies in particular. For a start, it reinforces the patchwork-quilt character of Europe's drug market, in which central authorization through the European Medicines Agency permits marketing in every member state, but which is frustrated by the divergent national pricing and reimbursement rules. A permit to market does not mean that the product will be marketed: that will depend uniquely on the deal that is – or isn't – reached between the manufacturer and the national authorities in each country.

The Belgian reticence over the prices agreed is another characteristic of the European market. Companies may well set an official or public price (and often do), but they often then reach an agreement with individual countries' health authorities to supply the product at a lower price or under certain conditions. But a concessionary price is granted only on condition that the price remains confidential – so as to preserve the company's room for manoeuvre in negotiating the price in other countries. Otherwise, no deal. Belgium is one of the EU countries that has taken a lead in trying to counter this system, because it leaves national authorities in the dark about what the going price is for a new medicine. But talks with the Netherlands, Luxembourg and Austria over reaching a common approach to price negotiations have yet to lead to any real action.

The further gap is one that is exercising many of Europe's strategists in cancer therapy. They feel that current arrangements for evaluating an innovative medicine's effectiveness are still inadequate – and particularly for immunotherapies, which are frequently administered in combination with other medicines. National health technology assessment bodies rarely coordinate on such evaluations, and when they do the coordinated approach usually omits the economic dimension. At the same time, companies are typically reluctant to engage in common evaluations of combinations involving their products.
 
And evaluation procedures tend – by their nature with innovative products – to be short-term, with conditional or accelerated authorizations dependent only on promises of some data in the future. As a result, long-term survival data are often lacking – making any coherent and comprehensive assessment of value difficult or even impossible.
 
This complex conundrum is increasingly recognized as a real challenge in Europe. But so far, there are few organized attempts to tackle it in all its dimensions.

Peter O’Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.