Clinical research is generally driven by the need to provide a solution to an unmet medical need. We all know that the expensive pathway between the ‘eureka’ moment (discovery of a new molecule) and the implementation on the market can take up to 15 years. Within this timeframe, a cascade of studies is initiated (efficacy, safety and optimal dosing) to obtain regulatory approval.

The market access teams will then take over the core activities in order to bring the innovation to the market at a well-balanced cost versus clinical benefit. No need to emphasize that, once launched, the limited time till patent expiry (5 – 7 years) will be used to gain back the financial efforts. Every month counts, for the companies as well as for the patients.

For some molecules, the clinical benefit as reported during clinical studies is recognised as addressing an unmet medical need. In such cases, the regulatory bodies can decide to initiate a ‘fast track procedure’ resulting in an accelerated assessment procedure and/or a conditional marketing authorisation. In general, these procedures can be installed when no alternative treatments are available or when a major therapeutic improvement versus current standard of care has been demonstrated.

For most molecules (and indications) the regulatory bodies will follow the standard regulatory and reimbursement procedures and alternative pathways need to be explored to bring the innovation to the patient more quickly:

• The company can bring the product to the market without reimbursement. This ‘out of pocket’ (OOP) situation is of course not the most ideal situation. An ethical debate can arise for patients with fewer financial resources. On the other hand, as the product is on the market, companies can distribute (a limited number of) samples and prescribers can start to use the product in their clinical practice. In general companies will submit a reimbursement request in parallel, and the OOP situation is usually temporary.
• A classic price and reimbursement procedure can be initiated before regulatory approval (at time of positive CHMP opinion which is +/- 2 months before the EMA approval). As a condition to fulfil, the company has to prove clinical benefit and submit their file as a ‘Class 1’ procedure.
• Regardless of the submission for reimbursement, a company can decide that patients should have faster access to their innovation. One option is to submit a request for an ‘Early Access Program’ (EAP) in line with the Royal Decree of April 25, 2014. Following an Early Temporary Authorisation (ETA) procedure, a compassionate use program (CUP, for drugs with no MA) or a Medical Need Program (MNP, for drugs with MA for at least one indication) can be set up, allowing the innovation to enter the market before EMA approval or reimbursement.

Both programs can only start after approval by an ethics committee that has analysed the inclusion and exclusion criteria, the patient information, and the elements which will be collected during the program (usually limited to pharmacovigilance-related data).

In the context of an EAP, the company will provide the treatment drug for free as long as no reimbursement is granted (until reimbursement, refusal of reimbursement or if the company decides to discontinue the program in light of newly emerged scientific evidence).

The company faces certain risks, as there is no guarantee of a successful reimbursement procedure. For this reason, the company can define the maximum time that the patient can benefit from the treatment for free, usually aligning with the treatment duration in the pivotal trial(s). If no treatment duration is defined, the company should continue to provide the drug for free as long as the treating physician deems this necessary.

Additionally, reimbursement can be limited to a subpopulation, and as such, some patients included in the Medical Need or Compassionate Use Programs might not have access to reimbursed drug; the company should then continue to provide the drug for free for the planned duration, or as long as the treating physician deems this necessary.

Good to know: An EAP can be initiated several months (years) before reimbursement and the program should be limited to one indication (or a subgroup within the indication).

• Another option would be Early Temporary Reimbursement (ETR). Companies can ask the authorities to include the indication in question on a list (updated on an annual basis); a commission will decide if the criteria are met (limited to severe and life-threatening diseases), and the ranking of the indication compared to other indications with Unmet Need. If the indication is included on the list, the molecule can benefit from ETR and the molecule in question will be reimbursed for 100%. A potential limitation can be that a subgroup of patients (versus full indication) will benefit from the ETR.
• A recent change in legislation came into force for ETR, in line with the Royal Decree of January 6, 2021. In this case, the NIHDI will reimburse the product in case of exceptional circumstances in which the government is forced to do so. This is only possible after a short proposal process (steered by the CRM) without interaction with the company and will be recognised (or not) by the Minister for Social Affairs and Public Health. This can be a solution in exceptional and urgent cases like pandemics.
• And of course, urgent requests for compassionate use (for medicinal product without any authorisation) remains possible in exceptional cases, as per Art. 107/1 of RD 14 December 2006.

As you can read in this article, there are a lot of possible options. It is important to outline a smart strategy before the product is brought to the market. Early Access can result in a higher uptake of patients ‘on treatment’ at the start of conventional reimbursement. This can influence the conditions of a Managed Entry Agreement, as well the market shares of competitors and last but not least, this will impact the procedural timelines and launch readiness.

In addition to the strategic decisions, a lot of regulatory & reimbursement specific procedures need to be respected and the available packaging (drug units) need to be launched in line with legislation (specific label requirements for MNP/CUP packages versus commercial packaging).

No need to worry, (our) experts are happy to brainstorm together with you to select the most optimised route to bring your innovation to the market.

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