By Anastasios Pappas, Senior Analyst (Health Advances GmbH)
- After having been assigned no incremental benefit vs standard of care, both approved PCSK9 inhibitors were initially explicitly excluded from prescription in Germany
- Subsequent intense negotiations between the German national HTA body, medical societies, and the manufacturers led to selected reimbursement for those subpopulations in which use of PCSK9 drugs offers a benefit versus their current standard of care
- Despite manufacturers working years on generating world evidence, there are still reimbursement restrictions for the two PCSK9 agents in other large European markets such as France, UK, Italy and Spain
- The above-mentioned reimbursement restrictions in EU countries have had a substantial impact on the commercial uptake of the drugs
- Manufacturers should be prepared for more meticulous approaches in reimbursement, such as increasingly sophisticated patient segment analysis, and should consider the importance of getting HTA advice early
The PCSK9 inhibitors alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen) were approved in Europe in late 2015 based on their impressive reduction of LDL-cholesterol in clinical trials. However, the reliance on this surrogate endpoint while lacking hard cardiovascular outcomes data, and their high price compared to generic statins have sparked intense discussions about their value.
German Drug HTA and Reimbursement
In 2016, the German HTA authority G-BA assigned ‘no added benefit’ to both PCSK9 inhibitors vs generic statins – the well-established standard of care. Such a verdict normally results in automatic reference pricing, limiting the maximum achievable price for a drug in Germany to the price level of the comparator.
Following the HTA outcome, the G-BA had explicitly excluded both PCSK9 drugs from prescription – a measure unprecedented in Germany and justified by the high annual therapy cost of ~EUR 10’000 as well as the lack of incremental clinical benefit. While this initial outcome would have meant no potential for revenues in Germany for both drugs, negotiations between the G-BA, the manufacturers of both drugs, medical associations and other expert groups brought about an exceptional solution. While prescription of both drugs is still banned for most subpopulations, both substances can be prescribed for patients with hereditary familial hypercholesterolemia and patients with mixed dyslipidemia which are not sufficiently controlled after 12 months of the highest dose of statin therapy. Both these patient groups would qualify for LDL blood apheresis, a procedure associated with higher costs than the PCSK9 drugs.
PCSK9 Reception in Other Countries
Similarly, France, UK, Italy, and Spain have restricted the reimbursement of PCSK9 to the highest risk dyslipidemia patients after long price negotiations. Praluent has been excluded for reimbursement after its first evaluation by Transparency Committee in France. It only gained positive reimbursement for the highest risk patients in mid-2017, whereas the price negotiations concluded at the end of January 2018.
In the UK, both drugs are recommended by NICE only for patients with high risk of cardiovascular disease or with hereditary high cholesterol levels.
The global net sales of both drugs have been less than $300 million in the first nine months of 2017, a number well below expectations, as analysts originally estimated these to become blockbusters which would generate combined revenues of approximately $2 billion in 2017.
The unprecedented reimbursement approach for Praluent and Repatha can be seen as a trend to carve out clear and quantifiable health economic benefits for distinct patient groups with high-unmet needs and/or high consumption of healthcare.
About The Author
Anastasios Pappas is a member of Health Advances European Practice Area, which helps clients navigate through the diversity of European healthcare systems to optimize commercialization strategies of pipeline and in-market products.
G-BA, Kassenaerztliche Bundesvereinigung, FiercePharma, HAS, Market Insider, Reuters, JP Morgan