Since the mid 2000s, GENENTECH / NOVARTIS’ LUCENTIS™ (ranibizumab) has enjoyed regulatory approval and funding across the USA and major EU markets for age-related macular degeneration (AMD). With strong efficacy and safety profiles as well first-to-market timing of marketing authorisation and funding, LUCENTIS is a presumptive market leader in the AMD space. However, an unlikely competitor has steadily increased as a competitive threat to LUCENTIS: AVASTIN™, another VEGR angiogenesis inhibitor, which is approved for use in multiple types of cancer but is largely unstudied and unapproved for AMD. Around the world, AVASTIN’s lack of marketing authorisation in AMD has not prevented prescribers from using it for AMD on a discretionary basis; with a similar molecular structure and a similar mechanism of action to LUCENTIS but a lower per-injection cost, some clinicians prefer AVASTIN over LUCENTIS for AMD.
This unusual trend has not gone unnoticed by manufacturers or government payers. In June 2014, Italy’s government took a bold stance in addressing this issue: they announced that they will fund the use of AVASTIN in AMD despite its lack of marketing authorisation from the EMA. Similarly, in July 2014 France’s government issued a similar law allowing the prescription of AVASTIN in AMD even without regulatory approval. Although the economic motive for this behaviour is clear, the regulatory and ethical justification is far more tenuous; EMA approval generally dictates approval at the country level, and so the decision of these government payers to grant regulatory and reimbursement at once is a decisive move to buck this trend.
For pharmaceutical stakeholders who have long been required to adhere to strict regulatory requirements regarding discretionary use, it appears incongruous to see federal governments supersede their own long-standing legal and regulatory bylaws just for the sake of economic expedience. Moreover, on a clinical level, this type of action exposes patients to unknown risks: regulatory approval is designed to ensure that pharmaceutical products are safe to employ in a given indication, and to ignore this regulatory precedent is to neglect a fundamental duty to protect patients and advise clinicians. Such risks are particularly evident in this case, as LUCENTIS has been developed and formulated specifically for intravitreal injection while AVASTIN has not, and so the safety risks associated with this difference in administration have not been adequately considered by the EMA, and perhaps not even by local country regulators.
With this type of development taking place, the already complex environment of global market access takes on yet another layer: country-level marketing authorisations in Europe have customarily mirrored authorisations at the EU level from the EMA, but Italy and France’s medicines agencies here demonstrate a willingness to undermine this process in the name of budgetary interests. This action clearly sets an ominous precedent; if countries like Italy and France can override the manufacturer’s wishes in one case, they effectively reserve the right to do so again in the future. This can have serious consequences for future cases of discretionary use as well as broader applications, including biosimilars, and the industry will be on the lookout for this kind of action as it unfolds.
Theodore Schroeder is a Senior Analyst in CBPartners’ Pricing and Market Access practice.