To truly understand Medicines Adaptive Pathways to Patients (MAPPs) from a regulatory perspective, it’s essential that we take a closer look at the building blocks – both old and new – that are paving the way for its implementation, says Sabine Atzor, Director Regulatory Affairs, part-time seconded from F.Hoffmann-La Roche to EFPIA. 

“People think MAPPs is something totally new but it isn’t,” says Atzor, explaining, “It is a new approach or philosophy on evidence generation, including real world data that is built on a number of existing regulatory and cooperation tools. The objective is to achieve early access to medicines for patients for which no satisfactory therapy exists. And to really understand MAPPs, it’s important to understand these so-called ‘building blocks’ that support it, how they can be applied in a complementary manner and how regulators, HTA bodies, patients and companies will interact in the future.”

While MAPPs is not about looking at some “magic moment” in which the product is authorised in the first place, but rather at evidence generation over the life cycle of a medicine, a number of existing regulatory tools – as well as new ones on the horizon – underpin its operations. Early and frequent scientific dialogue, parallel or joint scientific advice between regulatory and HTA bodies, and conditional marketing authorisation are some the tools that will support MAPPs, says Atzor.

Conditional marketing authorisation – in theory and in practice

One MAPPs “building block” that Atzor highlights is the conditional marketing authorisation. This, alongside an accelerated assessment process, aims to help speed access for patients to innovative medicines in disease areas where no treatment is available or where a major therapeutic advantage is available over existing treatments.

“The tool is there – but it has been underused and is considered not very attractive by industry,” says Atzor, pointing to the Escher Report published in September 2014. This Report described a number of problems standing in the way of pharmaceutical companies best utilising the conditional marketing authorisation. “The system seemed to have worked well for certain products – but did not work well consistently across therapeutic areas, notably in the area of oncology, or was even not applied in others” says Atzor.

Following the Escher Report, which identified gaps in the current system, a small team of experts from EFPIA member companies took a deep dive into the root cause of the problems through a thorough analysis of past cases from companies. As a next step, the team developed options to address existing gaps and shortcomings. EFPIA finally endorsed these as the: “EFPIA Proposal for Options to Improve the Application of the Conditional Marketing Authorisation System in the EU (not requiring legislative changes)”.

EMA public consultation on revised guidelines on accelerated assessment and conditional marketing authorisation

A two-month consultation by the EMA on revised guidelines regarding the implementation of both conditional marketing authorisation and accelerated assessment concluded on 30th September; EFPIA submitted its comments.

Asked about her views on the EMA guidelines, Atzor responds these draft revised guidelines reflect a substantial change of mindset by the regulators. It shows the strong will by the EU Network to advance the system for providing early access to patients. Most importantly, this move takes place within the limits given through legislation. This approach promises swift resolution.

The “conditional marketing authorisation” is the key regulatory tool for early approval in situations of unmet medical need in seriously debilitating or life-threatening diseases on the basis of less comprehensive data, in particular for safety and efficacy. Traditionally, the scheme has been applied in very limited therapeutic areas, such as oncology or medicines to treat HIV. EFPIA takes the view that the interpretation on what constitutes a seriously debilitating disease should be much broader and also include, for instance, Alzheimer’s or Parkinson’s disease, notes Atzor.

Given the existing regulatory tools, there is a need to take a renewed look on how uncertainty can be managed. This need increases with the expectation of more targeted medicines in the future for which strong efficacy data can be generated with a limited number of patients as opposed to large randomised controlled trials. This can justify an early approval but may leave a degree of uncertainty on safety, i.e. side effects. This needs to be carefully managed after approval, for instance through specific obligations including, e.g. further studies or real world data collection in registries.

It will be important to continue scientific discussion on what evidence is reasonably likely to translate into a clinical benefit and a positive benefit-risk conclusion on a given medicine to address unmet need in specific therapeutic areas.

Products submitted for a conditional marketing authorisation should automatically qualify for an “accelerated assessment” of 150 days (vs. 210 days). This system should be more flexible in the future to include elements of a “rolling review”, which allows submission of data in incremental steps and a swift decision after the final submission date.

While the revised conditional marketing authorisation guideline largely includes the above important improvements, EFPIA is calling for more streamlining of administrative provisions related to the annual renewal and specific obligations and expand the possibility of using the scheme for type II variations.

Once adopted, EFPIA plans to carefully monitor the impact of the revised guidelines in practice.

Looking ahead – a new building block to underpin MAPPs

Asked what lies ahead, Atzor mentions an early consultation meeting at the EMA to discuss the proposed “new scheme to support development of innovative medicines for unmet needs” following earlier discussions by the Agency on what was called  a “European Early Stage Innovative Medicines Designation” as part of the draft EU Medicines Agencies Network Strategy to 2020 and an earlier “Pathfinder Scheme”.

EMA is developing a scheme based on enhanced interaction and early dialogue with medicine developers to facilitate the development and accelerated assessment of innovative medicines of major public health interest. The eligibility criteria that are used in the accelerated assessment procedure are being considered for this new scheme. Further details, including eligibility criteria, possible procedures as well as incentives offered by the scheme are still under discussion, with finalisation and launch planned for the first quarter of 2016.

“It’s another building block that can help progress MAPPs,” says Atzor. Emphasising the need for flexible dialogue and interaction going forward, she adds: “Industry is pleased to see the EU Network’ s committment to progress things. We have the high expectation that, complemented with such a new scheme, the EU system will be equally successful as the Breakthrough Designation in the US in delivering innovative medicines for patients early.  But Europe is more complex and the boat will only reach the destination if all stakeholders assign the most experienced sailors.”