UK MHRA To Retain Multiple Approval Pathways From 2025

The UK medicines regulator, the MHRA, plans to continue offering new drug authorizations through numerous pathways, including national approvals, reliance routes and worksharing initiatives, when it becomes responsible for UK-wide licensing of new medicines on 1 January 2025.

The agency told the Pink Sheet that its approach to assessing drug marketing applications would involve a balance of three assessment methods – national reviews, cooperative efforts with international counterparts, and reliance on overseas evaluations.

Since leaving the EU in 2020 and later becoming responsible for new drug approvals in Great Britain (England, Scotland and Wales), the MHRA has made full use of the reliance procedures. 

That said, it notably used its national assessment procedure for two first-of-their-kind products – the gene-editing therapy, Casgevy, and the Alzheimer’s disease drug, Leqembi.

As of January next year, the MHRA will be able to issue marketing authorizations (MAs) with validity across the UK (ie, including Northern Ireland) as a result of the Windsor Framework agreed in 2023.

Reliance A Key Route Used By MHRA

In addition to the national route, the MHRA has been able to approve new drugs via the European Commission Decision Reliance Procedure (ECDRP), the Decentralised and Mutual Recognition Reliance Procedure (MRDCRP), the International Reliance Procedure (IRP), Project Orbis and the Access Consortium. The ECDRP and MRDCRP were superseded by the IRP in January this year.

The ECDRP applied to new drugs falling within the scope of the EU centralized procedure and allowed the MHRA to rely on approval decisions taken by the commission on the basis of a positive opinion from the European Medicines Agency’s human drugs committee, the CHMP. 

The MRDCRP was used for products that were authorized in the EU under non-centralized procedures.

First-Half New Active Substance Approvals

In the first half of 2024, for example, the agency relied on an EU decision for 15 of the 16 marketing authorizations it granted for products containing a new active substance (NAS).

For 13 of those, it used the ECDRP.  Another product was approved following a submission under the MRDCRP. This was RUBY-FILL (rubidium Rb 82 generator), a radiopharmaceutical for imaging of the heart, which the MHRA classifies as a medicinal product and a NAS. According to the EMA (16 May 2024), in the EU the product was approved at national level in just two countries: Germany and Luxembourg.

One approval – for Advanz Pharma/Allecra Therapeutics’ Exblifep (cefepime/enmetazobactam) – was granted via the new IRP, which involves the EU and several more international reference regulators. (Also see "UK’s New International Recognition Procedure A ‘Win-Win’ For Stakeholders" - Pink Sheet, 2 Jan, 2024.)

The one product approved by the MHRA in the first half that did not rely on an EU procedure was Progit (itopride), a gastroprokinetic drug from the Czech company Pro Med CS Praha AS. While the MHRA classifies Progit as a NAS, in the EU it is approved at national level and only in some eastern European and Baltic countries.

Use Of IRP To Continue

The IRP allows the MHRA to take into account the expertise and decision-making of trusted regulatory partners –  from Australia, Canada, the EU/EEA, Switzerland, Singapore, Japan and the US.

The MHRA told the Pink Sheet that it would “continue to offer the IRP as a regulatory route to marketing authorization (MA) when UK-licensing is implemented for all new medicines under the Windsor Framework on 1 January 2025.”

As to how the IRP facilitates drug approvals, the agency explained that it allows it to take into account the “expertise and decision-making of trusted regulatory partners listed in our guidance.” The MHRA “will conduct a targeted assessment based on eligibility and triage of IRP applications and retain the authority to reject applications if the evidence provided is considered insufficiently robust or [the] application provided does not take account of UK requirements.”  

It noted that there are two recognition timetables for new IRP MA applications: Recognition A (a 60-day timetable) and Recognition B (a 110-day timetable). “Eligibility for Recognition B reflects the additional assessment time required, for example, applications for conditional marketing authorization or orphan drug designation, where UK-specific criteria must be met,” it added.

Asked whether the MHRA would eventually conduct its own full assessments of all new drugs, it said its priority was to “conduct a balance of national, collaborative and IRP reviews” – the collaborative reviews being Project Orbis and the Access Consortium.

Project Orbis involves near-concurrent and collaborative assessments of cancer drugs by regulators from Australia, Brazil, Canada, Israel, Singapore, Switzerland, the UK and the US. The ACCESS Consortium comprises regulators from Australia, Canada, Singapore, Switzerland and the UK, and involves one participating regulator taking the lead on the assessment of approval submissions.

To date, 10 initial marketing authorization applications have been approved by the MHRA via Project Orbis, and three via the Access Consortium.

National Assessments A Key Route To Approval

The national route will also remain an important regulatory tool for the MHRA, which said that over the past 12 months it had continued to assess some medicines nationally.

One notable example was the gene-editing therapy, Casgevy (exagamglogene autotemcel), from Vertex Pharmaceuticals/CRISPR Therapeutics, for sickle cell disease and transfusion-dependent β-thalassemia. The UK approved the product in 2023, becoming the first country in the world to approve gene editing as a potential cure for two inherited blood disorders.

Another example was Leqembi (lecanemab), Eisai/Biogen’s Alzheimer’s treatment. The MHRA approved the drug, the first that can slow down early-stage Alzheimer’s disease, in August, although its availability on the National Health Service in England hangs in the balance after its reimbursement was provisionally denied. (Also see "Leqembi's UK Rollercoaster: A Yes From MHRA, A No From NICE" - Pink Sheet, 22 Aug, 2024.) Leqembi was rejected by the EU regulator in July – a decision that Eisai is contesting. (Also see "EU Blow For Alzheimer’s Drug Leqembi; Eisai To Appeal" - Pink Sheet, 26 Jul, 2024.)

“The core mission of the agency is to promote innovation and protect public health, and national assessment plays a fundamental role in this,” the MHRA declared.

“We recognize that access for UK patients can be expedited through use of the national assessment timetable,” where approval by only one regulator (the MHRA) is needed, “rather than two for a recognition procedure,” it said. The IRP “will therefore continue to be offered as a regulatory route to MA, along with national, Access and Project Orbis routes. Eligibility for each route is based on certain criteria.”

The agency also pointed out that it offers pre-submission regulatory advice to help companies decide on their regulatory strategy for each new medicine. “These discussions form part of pipeline and pre-submission meetings, with the overall goal of facilitating timely patient access to innovative medicines, particularly in areas of high unmet need or public health importance.”