We need a sustainable, innovative model for unmet medical needs
How can we deliver a sustainable and innovative model for unmet needs? By focusing on drug repurposing, publicly funded clinical trials and third party licensing.
Drug repurposing, defined as a strategy for identifying new uses for approved drugs outside the scope of the original application, is a drug development strategy that was already widespread before COVID-19 revealed its potential to the general public. Drug repurposing has the potential to reduce both time and cost, as existing data on how a drug can be used, including safety and toxicological data, reduce the need for early phases of drug discovery. In addition, some studies have suggested that time-to-market can be halved and costs reduced even more – and with a reduced risk of failure.
If this developmental strategy is applied for unmet medical needs it will still require thorough clinical research in areas that are less commercially interesting. In case the drug is patent-protected this lack of commercial interest can be explained by the fact that the new indication is outside the therapeutic focus of the patent holder or because the indication is too rare and projected revenues too low with the danger of off-label use looming around the corner when rebranding comes with a substantial price increase. In case of generic drugs, the generic market authorization holders are lacking incentives to contribute to clinical research for new indications because competition drives their prices down and does not allow them to recover the cost of the research. Moreover, generic competitors could “free ride” on the approval of a new indication obtained by one manufacturer since prescription of generic drugs is not brand-based.
The COVID-19 pandemic has highlighted that when fast access to therapeutic solutions is imperative, patient-centered, independent clinical trials (e.g. Recovery trial) evaluating multiple existing drugs at the time, delivered meaningful results. Moreover, these investigator-driven trials were funded by government and philanthropic organizations. Today, the majority of clinical trials making use of existing drugs for new indications with high unmet need (e.g. rare cancers) are conducted by non-commercial actors but they lack reliable funding, regulatory assistance and incentives for further development.
Publicly funded trials
When these publicly funded clinical trials – which should meet the same strict conditions as commercial ones – produce conclusive results, current European legislation does not allow these possible new indications to be registered by third parties at the level of the European Medicines Agency (EMA). In short, the final step to fulfil the unmet medical need is missing in this instance, as only Market Authorization Holders can apply for a label extension. Therefore, the upcoming revision of the pharmaceutical legislation in Europe should consider a mechanism to evaluate results from investigator-initiated trials without the involvement of the Market Authorization Holder.
Without the possibility to have an indication registered by a third party, the prescribing and treating doctor can only prescribe 'off-label'. The off-label prescribing belongs to the therapeutic freedom of the doctors but the use should be carefully considered and the patient well informed. After all, there is often no certainty that the off-label use is safe and effective, or at least, the benefit/risk in an off label indication is not clear to the patient, and the off label use may, depending on the member state, imply non-reimbursement. Moreover, in Europe this is currently managed at the national level and leads to inconsistencies (e.g. reimbursement). A procedure that enables better and responsible off-label use could be established through the new joint Health Technology Assessment initiative in Europe but therefore third parties should be allowed to submit their mature clinical data on treatments that could alleviate an unmet medical need for Joint Clinical Assessment.
All this is in the interests of the patient (faster access to innovation and transparence about benefit/risk), the healthcare provider (therapeutic freedom and risk reduction) and health insurance (more efficient spending and unmet medical needs covered).
During the Slovenian presidency in 2021 repurposing of medicines in oncology was a major health topic (1) and during the French presidency the creation of a global cancer fund was a recommended action. Such a structural European fund could finance independent clinical research, comparable to the National Cancer Institute in the US that has proven to yield interventions with big public health benefit. The fund could partly be plenished by Member States and industry. Belgium has already made a number of attempts to put the important topic of 'third party licensing' on the European agenda and these efforts should be continued in 2023. During the Belgian Presidency in 2024, Belgium has a unique opportunity to organize a constructive dialogue with the pharma industry on access to valuable treatments resulting both from commercial and non-commercial development.
In conclusion, part of the solution for unmet medical needs could come from non-commercial research using existing, registered drugs. Public investment in well-conducted investigator-driven clinical trials should be able to result in authorized medicinal products that can be used outside the terms of the original marketing authorization without the need of substantial investment from the Market Authorization Holders.
Note that we do not advocate focusing on repurposing at the expense of “de novo” development efforts but as an additional parallel strategy to increase the number of affordable treatments available to patients in need.
(1) Repurposing of medicines – the underrated champion of sustainable innovation. Policy brief. Copenhagen: WHO Regional Office for Europe; 2021. Licence: CC BY-NC-SA 3