Unlocking the potential of established products: toward new incentives rewarding innovation in Europe

Abstract

Background: Many established products (EPs – marketed for eight years or more) are widely used off-label despite little evidence on benefit–risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies.Methods: Targeted literature search and expert panel meetings.Results: Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients’ access to treatment options.Conclusion: There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems.

On-Label or Off-Label? Overcoming Regulatory and Financial Barriers to Bring Repurposed Medicines to Cancer Patients

“…This means that the 10-year exclusivity period can only be granted once per active substance that is the subject of a marketing authorization held by the same marketing authorization holder. In order to allow companies to recoup investments for the development of new indications for marketed therapies, some additional regulatory exclusivities have been established in Europe ( Figure 2) (Langedijk et al, 2016;Nayroles et al, 2017). First, the marketing authorization holder can be granted one additional year of marketing protection for one or more new therapeutic indications, with significant clinical benefit in comparison with existing therapies, applied for during the first 8 years (European Commission, 2007a).…”

“…The next essential step in bringing a treatment to the patient is setting the price and deciding on the reimbursement of the medicine, which takes place at the national level in the EU and varies across countries (Murteira et al, 2014b;Minghetti et al, 2017). When a new indication is introduced, the pricing of the existing medicine may be re-evaluated and renegotiated in some countries, like France, Italy, and Spain (Nayroles et al, 2017). The introduction of a new indication for a product that was already on the market can lead to price cuts because of a combination of price/volume agreements, external reference pricing, or budget impact analysis (Nayroles et al, 2017).…”

“…When a new indication is introduced, the pricing of the existing medicine may be re-evaluated and renegotiated in some countries, like France, Italy, and Spain (Nayroles et al, 2017). The introduction of a new indication for a product that was already on the market can lead to price cuts because of a combination of price/volume agreements, external reference pricing, or budget impact analysis (Nayroles et al, 2017). In contrast, a company could ask for an increase in price to compensate for the investments made to develop the new indication, but payers are generally resistant to pay a higher price for a new indication of an existing medicinal product (Shineman et al, 2014; STAMP European Commission expert group, 2017a; Toumi and Rémuzat, 2017).…”

“…In addition, applying for marketing authorization of a new indication can place a high administrative burden. The product label and pharmacovigilance system need to be updated for a new indication (STAMP European Commission expert group, 2017a) and, in some cases, a risk management plan or a pediatric investigation plan (PIP) has to be submitted (Nayroles et al, 2017).…”

“…Pharmaceutical companies often choose not to invest in new therapeutic indications after expiry of basic patent and regulatory protection periods of their approved products (Langedijk et al, 2016;Nayroles et al, 2017). Patent claims for secondary uses often offer weaker protection compared to the primary basic product patent claims so the risk of free-riding by competitors is high (Sachs et al, 2017).…”