Regulatory Round-up - June 2024

UNITED KINGDOM

National Institute for Health and Care Excellence (NICE)

Etranacogene Dezaparvovec For Treating Moderately Severe or Severe haemophilia B is being made available on the NHS

Hemgenix (etranacogene dezaparvovec) will soon be available to eligible patients in England with severe and moderately severe haemophilia B (congenital factor IX deficiency) who have no history of factor IX inhibitors. This therapy will be NHS funded via the Innovative Medicines Fund over a ten-year managed access period with further data collection to resolve the current uncertainty over its long-term benefit.

This has great importance for the improvement of standards of care for appropriate haemophilia B patients, with this innovation being the first gene therapy available for this condition that addresses the underlying cause of the condition. Please find further information here.

Medicines and Healthcare products Regulatory Agency (MHRA)

Guidance On Centrally Authorised Products (CAPs) Bridging Mechanism

This guidance applies until the Windsor Framework takes effect on 1 January 2025. Under the Windsor Framework, rather than novel medicines for use in Northern Ireland requiring an application to the EMA, the MHRA will assess applications and license all products in the scope of the EU’s Centralised Procedure on a UK-wide basis. Until the Windsor Framework is implemented, decisions taken by the EC on the approval of new Marketing Authorisations (MA) in the centralised procedure will continue to be applicable to Northern Ireland, in accordance with EU law. MAs issued by the EC in relation to Centrally Authorised Products (CAPs) are not valid in Great Britain (GB) and a separate national application is needed for GB. Therefore, there is a possibility that in the case of parallel applications to the EMA and the MHRA, the MHRA will issue an MA for a medicinal product before an MA has been granted for the same medicinal product in the EU. In this case, under a CAP bridging mechanism, companies will be able to supply a GB licenced product (PLGB) to Northern Ireland for a period of 6 months, or until the EC authorises a CAP in Northern Ireland, or the EC refuses an application for the product, whichever is sooner. This will help to ensure that patients in Northern Ireland have access to those medicinal products at the same time as patients in other parts of the UK. The CAP bridging mechanism is part of an EU legislative package for medicines passed in April 2022.

EUROPE

European Medicines Agency (EMA)

Two new advice pilots to improve clinical trials in Europe

The Accelerating Clinical Trials in the EU (ACT EU) initiative has launched two advice pilots aimed at improving the quality of applications for clinical trials, the foundation for the development of safe and effective medicines in Europe.

The first pilot offers developers of medicinal products scientific advice on clinical trials and on requirements for marketing authorisation applications (MAA).

The second pilot is coordinated by the CTCG and provides technical and regulatory support on the dossier of a CTA prior to its submission through the Clinical Trials Information System. The pre-CTA pilot will provide consolidated views of the Member States concerned on pre-submission topics.

Developers of medicinal products who wish to receive advice on the requirements for a MAA or a CTA can now apply to these pilots. Please find further information here.

EMA's CHMP Issues Positive Opinion on Pfizer's Haemophilia B Gene Therapy

EMA has adopted a positive opinion, recommending the granting of a conditional marketing authorisation for Durveqtix (fidanacogene elaparvovec), branded as Beqvez in the US to treat severe and moderately severe haemophilia B in adults who do not have factor IX inhibitors (auto-antibodies produced by the immune system against (factor IX replacement medicines) and who have no detectable antibodies to variant adeno-associated virus serotype Rh74 (AAVRh74var). Please find further information here.

Faster access to clinical trial information in Europe

The launch of a new version of the Clinical Trials Information System (CTIS) will allow earlier and more efficient access to information about clinical trials in the European Union (EU) for patients, healthcare professionals and other stakeholders. This is due to the revised transparency rules that became applicable on the 18^th June 2024 in Europe. One of the key changes is the earlier availability of information on authorised clinical trials. The new rules eliminate the previously available deferral mechanism, which allowed clinical trial sponsors to delay publishing certain data and documents for up to seven years after a trial’s completion to protect commercially confidential information. Under the new rules, approximately 4,000 clinical trials with issued decisions are now publicly accessible through the CTIS search. The updated rules strike a balance between transparency of information and protection of commercially confidential information. A user guide and an overview are available for Sponsors to understand these revised transparency rules.

Variations guidelines: Proposed amendments to the European Commission guidelines on variations categories and procedures

As part of the 2020 Pharmaceutical Strategy for Europe, the Commission is reviewing the current rules governing the procedures for post-authorisation changes to the terms of a marketing authorisation for human medicines, with the purpose to make the lifecycle management of medicines more efficient and future proof and ensuring the protection of public health in the EU.

EMA, the Heads of Medicines Agencies (HMA) and the EC are inviting pharmaceutical industry representatives and other interested parties to comment on the proposed amendment of the variations guidelines.

Consultation ends on 23 August 2024. Please find further information on how to submit comments and access to documents with the proposed changes here.

USA

Food and Drug Administration (FDA)

FDA Expands Approval of Gene Therapy for Patients with Duchenne Muscular Dystrophy

The FDA has expanded the approval of Elevidys (delandistrogene moxeparvovec-rokl), a gene therapy for the treatment of Duchenne muscular dystrophy (DMD) for ambulatory and non-ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene. Elevidys was previously approved under accelerated approval for ambulatory individuals 4 through 5 years of age with DMD with a confirmed mutation in the DMD gene. Please find further information here.

FDA issues draft guidances covering BIMO inspections

The FDA has issued two draft guidances on bioresearch monitoring (BIMO) inspections.

The first draft guidance entitled ‘Standardized Format for Electronic Submission for Marketing Applications Content for the Planning of Bioresearch Monitoring (BIMO) Inspections for Center of Biologics Evaluation and Research Submissions’ covers information to assist the agency in planning these inspections. This guidance should be read in conjunction with the BIMO technical conformance guide issued in August 2022, which covers the specifications for preparing and submitting clinical study information and subject-level data line listings by clinical sites.

The second draft guidance entitled ‘Processes and Practices Applicable to Bioresearch Monitoring Inspections Guidance for Industry’ covers best practices for communicating to the FDA before, during, or after an inspection.

Both cover sponsors that have submitted new drug applications (NDAs), biologics license applications (BLAs), and supplements.

OTP Town Hall: CMC Readiness for Gene Therapy BLAs

The FDA’s Center for Biologics Evaluation and Research (CBER) Office of Therapeutic Products (OTP) hosted the virtual town hall on 4^th June 2024, to answer stakeholder questions regarding the chemistry, manufacturing, and controls (CMC) information submitted with biologics license applications (BLAs) for gene therapy products. Experts from OTP’s Office of Gene Therapy CMC were available to answer questions. Please find the video recording of this event here.

Breyanzi: BLA Approval of New Indication

FDA approved lisocabtagene maraleucel for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Please find further information here.

International

Asia-Pacific Roundup: Hong Kong advances new Centre for Medical Products Regulation

Hong Kong’s Department of Health (DH) has created an office to prepare for the creation of the Centre for Medical Products Regulation (CMPR). The new preparatory office will propose steps for formally establishing CMPR. Please find further details here.

Public consultations

European Directorate for the Quality of Medicines (EDQM)

European Medicines Agency (EMA)

Food and Drug Administration (FDA)

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