Regulatory Round-up - June 2022

EUROPE

European Commission (EC)

EC, EMA and HMA publish joint Q&A intended to guide Complex Clinical Trials

On 2 June, the European Commission (EC), the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) published a joint Q&A intended to guide complex clinical trials (CCTs). The aim is that this document will give more clarity on how CCTs should be conducted. The document aims to answer some basic questions, such as what to consider in the planning and conduct of CCTs, how to justify Bayesian approaches to regulators, and how to use biomarkers.

Draft on Labeling Requirements for IMPs Published

With the application of the EU Clinical Trials Regulation No 536/2014 (CTR) some labelling requirements for IMPs have changed, in particular regarding the expiry date. According to these new requirements, the expiry date must be included on both the primary and secondary packaging of these products, without exception. Now, this initiative proposes to remove the obligation to include an expiry date on the primary packaging of IMPs in specific circumstances. The opportunity for public comment on the draft closed on 29 June 2022. More information is provided under Unauthorised medicinal products used in clinical trials (labelling rules).

European Medicines Agency (EMA)

First therapy to treat rare genetic nervous system disorder AADC deficiency

The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation in the European Union (EU) for Upstaza (eladocagene exuparvovec), a therapy for the treatment of adult and paediatric patients with severe aromatic L-amino acid decarboxylase (AADC) deficiency with a genetically confirmed diagnosis.

Upstaza consists of a modified virus (adeno-associated viral vector) that contains a functional version of the AADC gene. When given to the patient by infusion into the brain, it is expected that the virus will carry the AADC gene into nerve cells enabling them to produce the missing enzyme. This in turn is expected to enable the cells to produce the substances they need to function properly (such as dopamine and serotonin), thus improving symptoms of the condition.

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA joins international partnerships to set global standards for medicines and medical devices regulation

The UK is set to play a greater international role in making sure medicines and medical devices are regulated safely and efficiently worldwide, the MHRA announced they have been accepted as a full member of three international work-sharing partnerships. The MHRA has partnered with the International Medical Device Regulatory Forum (IMDRF) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) to share expertise with other leading organisations, and support the development of regulatory guidelines and drive greater harmonisation of regulation around the world.

The MHRA has also been accepted as a member of the US-based Medical Devices Innovation Consortium (MDIC). This public-private partnership brings together representatives of regulatory bodies, industry, non-profits, and patient organisations from different countries to improve the processes for the development, assessment, and review of new medical technologies. This enables transformational medical technology to get to the people who need it sooner, by shortening the path from innovation to safety to access.

British Pharmacopoeia

New best practice guidance on ATMP Flow Cytometry and Vector Copy Number

With complexity and risk associated with each stage of assay development, the Advanced Therapy Medicinal Products (ATMP) Flow Cytometry and Vector Copy Number best practice guidance offers a practical and phase-appropriate validation tool to help cell and gene therapy programmes to succeed. This new guidance has been developed and approved by the British Pharmacopoeia (BP), as part of the MHRA, in partnership with experts from the cell and gene therapy community including industry, the NHS and academia. This guidance document is available as part of the BP online and is now free to download.

USA

Food and Drug Administration (FDA)

FDA expands Breyanzi approval for relapsed or refractory large B-cell lymphoma to second line treatment and those ineligible for HSC transplant

The FDA approved lisocabtagene maraleucel for treatment of adults with relapsed or refractory large B-cell lymphoma after one prior therapy.

The approval applies to use of the agent by patients with refractory disease to first-line chemoimmunotherapy or who relapsed within 12 months of first-line chemoimmunotherapy, including those who are not eligible for hematopoietic stem cell transplantation due to comorbidities or age. The FDA previously approved the therapy for treatment of adults with relapsed or refractory large B-cell lymphoma who received two or more lines of systemic therapy.

The approval comes less than three months after Yescarta became first CAR-T drug to enter the second-line setting and a little over a year after Breyanzi’s original approval as a third-line therapy.

Spark updates Luxturna prescribing information with FDA for complications observed post-marketing

The FDA has approved an update to the voretigene neparvovec-rzyl (Luxturna) post-marketing experience section of the label to include the occurrence chorioretinal atrophy, observed in a subset of patients post-subretinal injection of the therapy.

FDA issues new draft guidance for industry on Considerations for Rescinding Breakthrough Therapy Designation

This new draft guidance explains how, during its evaluation of a drug development program, FDA may consider whether to rescind a breakthrough therapy designation (BTD). The FDA are accepting comments on the draft guidance until 23 August 2022.

National Institutes of Health (NIH)

Gene therapy for rare eye disease safe but lacks efficacy in early trial

An NIH-funded clinical trial showed little, if any, benefit for patients with Leber hereditary optic neuropathy (LHON). The therapy was designed to restore function of the ND4 gene by injecting viral vector (AAV2) carrying normal gene into participants’ left or right eyes. The researchers tested four therapeutic doses, each with a different concentration of gene vector. While this gene therapy approach to LHON may yield visual benefit for some patients, the effect is at best modest.

Public consultations

Medicines and Healthcare products Regulatory Agency (MHRA)

Food and Drug Administration (FDA)

Internation Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)