Although by their nature, niche cancers have relatively small drug-treatable populations; manufacturers of orphan-designated drugs may be more likely to negotiate higher prices because of the drug’s associated small market size in addition to the typically high unmet need for such indications, thereby increasing the market opportunity. However, as European healthcare budgets are increasingly tightened, developers of niche cancer therapies need to be ever more mindful of the market access hurdles they need to overcome in order for their drugs to reach their full potential. While there are many hurdles to successful penetration of cancer therapies identified within specific indications (as outlined in Decision Resources Group’s European Physician and Payer Forum reports 1, 2, 3) there are specific hurdles for therapies of niche and rare solid tumors (NRSTs) exemplified in Decision Resources Group’s European Physician and Payer Forum report entitled “Navigating Reimbursement and Maximizing Market Access for Niche and Rare Solid Tumors in the EU5, a syndicated primary market research product delving into market access challenges for therapies treating hepatocellular carcinoma (HCC), thyroid cancer, gastrointestinal stromal tumor (GIST), and neuroendocrine tumors (NETs). A significant finding from this report was that all premium-priced targeted agents approved for HCC, thyroid cancer, GIST, and NETs are subject to prescribing and/or distribution guidelines and controls across the EU5.


Further examples of market access restrictions, uncovered in the European Physician and Payer Forum report impacting EU5 medical oncologists’ prescribing for NRSTs were:

  • Over 40% of surveyed oncologists from Italy and the UK indicated national reimbursement conditions as the most limiting nonclinical factor restricting their prescribing for GIST.
  • 48% of surveyed oncologists in France and 73% of surveyed oncologists in Spain indicated guidelines or directives severely or somewhat restrict their ability to prescribe for thyroid cancer.
  • According to surveyed oncologists in the UK and Spain, 13% of their unresectable advanced HCC patients eligible for Bayer HealthCare/Amgen’s Nexavar do not receive Nexavar primarily because of cost or reimbursement-related reasons.
  • The majority of surveyed EU5 oncologists indicated that their prescribing of Pfizer’s Sutent and Novartis’s Afinitor for NETs would moderately to significantly increase if they were not faced with any market access or reimbursement-related restrictions.
  • The majority of surveyed oncologists from Italy, Spain, and the UK who treat thyroid cancer, GIST, HCC, and/or NETs indicated that they expect regional variation to severely or somewhat impact patient access to emerging therapies for these indications.

Payers across the EU5 interviewed for the report highlighted the delay between European approval of a new therapy and completion of country-specific pricing and reimbursement (P&R) negotiations as a major market access challenge to developers of NRST therapies. These delays are are most notable in Italy and Spain, highlighted by the ongoing P&R negotiations in these markets for Exelixis’s Cometriq for treatment of medullary thyroid cancer (MTC) (approved by the European Medicines Agency in December 2013). Although in Italy, innovative agents may be classed as C-NN while P&R negotiations are ongoing (such as Bayer HealthCare’s Stivarga for GIST and Cometriq for MTC), permitting immediate hospital use, interviewed Italian payers indicated that prescribing of C-NN-classified agents is low due to the strain that funding of these drugs puts on hospital budgets. Another challenge faced by drug manufacturers is ensuring that drug dossiers submitted to health authorities are complete, highlighted by Germany’s IQWiG (Institute for Quality and Efficiency in Healthcare) assessment of Stivarga (for the treatment of GIST) and AstraZeneca’s Caprelsa (for the treatment of MTC)—IQWiG concluded that it was not possible to determine the added benefit of these therapies due to insufficient data submitted, notably a lack of safety data and data outlining the impact of the drugs on patient quality of life.

Optimizing clinical trial design is critical to ensure a clear demonstration of NRST therapy’s clinical benefit and allows for a more straightforward benefit assessment by EU5 health authorities. The challenge for drug manufacturers is to select the most appropriate choice of comparator, trial primary end point, and to carefully consider the selected patient population. Interviewed payers and a large proportion of surveyed oncologists considered measures of disease progression as an appropriate end point for therapies for NRSTs, although without an overall survival advantage, a substantial improvement in disease progression would be required to secure favourable reimbursement.

There are a multitude of hurdles, prescribing restrictions, and monitoring procedures in place across the EU5 for prescribers of therapies for NRSTs, of which only a handful have been discussed here. For emerging NRST therapies to successfully enter European markets, it is essential for developers to have a keen understanding of individual EU5 reimbursement environments to optimize the likelihood of reaching the summit of the European market access mountain.


  1. The Battle Between Angiogenesis and EGFR Inhibitors in Colorectal Cancer: How Will Physician and Payer Attitudes and Decisions Shape this Market?
  2. The Dynamic NSCLC Market: How Will European Payer and Physician Attitudes Shape This Highly Lucrative Market?
  3. The Burgeoning Prostate Cancer Market in the EU5: How are Physicians and Payers Responding to an Expanding Arsenal of Therapeutic Agents?


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