Euro Roundup: MHRA aims to accelerate approval of lowest-risk clinical trials

The Medicines and Healthcare products Regulatory Agency (MHRA) has begun a streamlined notification scheme that is designed to reduce the time to approve the lowest-risk clinical trials by more than 50%.

Under the new scheme, MHRA will approve certain clinical trial authorization (CTA) applications within 14 calendar days, instead of the statutory 30 days. Stakeholders welcomed the notification scheme when it was proposed in a consultation. Most (74%) of the more than 1,000 respondents agreed with the idea, noting that the old approach to low-risk studies can lead to unnecessary delays and suggesting the scheme could significantly reduce the risk-averse culture among many public sector sponsors.

The scheme, which MHRA calculates will be open to 20% of initial CTAs, is the start of a broader push to overhaul the regulation of clinical trials in the UK.

“Clinical trials regulation should be flexible and risk-proportionate so that the regulatory requirements are geared to the risk that a trial presents,” June Raine, chief executive at MHRA, said in a statement. “Our new notification scheme is exactly that. It will reduce the time taken to get the lowest-risk clinical trials up and running without undermining patient safety.”

The scheme is open to CTA applications for Phase 4 trials and certain lower-risk Phase 3 trials. For a Phase 4 trial to qualify, all investigational medicinal products must be licensed and used according to the relevant UK, US or EU marketing authorization and be free from ongoing safety concerns such as clinical holds.

Phase 3 studies will be accepted if they are already approved in the USA or EU based on the same protocol, MHRA has approved a Phase 3 trial of the same drug in the same indication in the past two years, or the investigational medicinal products are licensed and used according to the relevant UK, US or EU authorization. Studies with complex designs, pediatric participants, pregnant or breastfeeding subjects, or first-in-class or advanced therapies are ineligible.

It is “in everyone’s best interest now to use the new scheme for all eligible trials,” Raine said, adding that the CTA pathway “will help give UK patients quicker access to the potentially life-saving medicines being studied.”

The change follows a period in which MHRA failed to meet its performance metrics. The time from receipt of a valid initial CTA filing to a first opinion from MHRA increased to more than 140 days over the summer. MHRA has taken actions to bring response times down and has been meeting statutory timeframes for all applications submitted since the start of September. The average time to first review was less than 25 days for September CTAs.

Press Release, Updated Guidance, More

EMA shares draft guideline on synthetic peptide development and manufacture

The European Medicines Agency (EMA) is seeking feedback on the rules covering the development and manufacture of synthetic peptides.

Synthetic peptides are at the interface of small molecules and proteins and are subject to specific quality considerations, the draft guideline explains. Certain aspects of the production, characterization, specifications and analytical control of the molecules are outside of the scope of the existing guideline on the chemistry of active substances.

The draft guideline is a complement to existing advice on the chemistry of active substances and provides information about solid phase peptide synthesis, fragment condensation and other topics specific to synthetic peptides.

The draft is based on the structure of the common technical document (CTD). For each section, the draft states whether there are specific considerations for developers and producers of synthetic peptides. The section of the draft on the description of the manufacturing process and process controls explains that the same standardized steps may be used several times in the production of synthetic peptides and they do not need to be described in detail each time, “provided it is clearly indicated where these steps are used in the overall manufacturing process.”

Impurities is another key section of the draft. EMA offers specific advice on impurities in the starting materials, substances formed during the production process and molecules resulting from degradation during manufacture and storage.

After the core section on the active substance, EMA has written a few pages about medicinal product considerations, using a biological medicine as a reference product and the requirements for clinical trial applications.

EMA is accepting feedback until 30 April.

Draft Guideline

EMA tweaks timelines for post-authorization centralized procedures in updated Q&A

EMA has updated its post-authorization procedural advice for users of the centralized procedure with new timelines for certain variation applications and the registration of post-authorization studies.

The agency previously asked for at least two months’ notice of an upcoming type II variation application for a new indication. Now, EMA says the product lead should “ideally” contact it six months before the submission.

EMA revised its advice on when to register their post-authorization studies too. The updated guidance recommends that marketing authorization holders enter their protocols “as soon as possible after their finalization and prior to the start of data collection.” The agency also tightened the timeline for entering public abstracts of results from “within one month” to “as soon as possible and preferably within two weeks after their finalization.”

The agency has also rewritten its answer to a question about when it will publish the risk management plan (RMP) summary on its website. EMA’s latest response asked applicants to include redacted versions for publication when submitting RMPs for evaluation with type IB variations.

“It is recommended that all necessary changes are implemented via anonymization and deletion directly in the RMP submitted for evaluation, rather than by redaction in the document for publication,” EMA wrote. The agency is asking applicants providing RMPs for other types of post-authorization procedure to extract certain information and submit it as “one stand-alone PDF document” via EudraLink.

EMA Guidance

CHMP recommends conditional approval of Pfizer’s PRIME program cancer therapy

EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended the conditional authorization of Pfizer’s BCMAxCD3 bispecific antibody Elrexfio (elranatamab) in multiple myeloma.

The recommendation covers the use of the drug, which was supported through EMA's PRIME scheme, in adults with relapsed and refractory multiple myeloma who have received at least three prior therapies. CHMP made the recommendation based on a Phase 2 clinical trial that linked Elrexfio to a 61% response rate, as well as a larger safety dataset.

Under the terms of the conditional authorization, Pfizer needs to submit data from a Phase 3 clinical trial of Elrexfio as a monotherapy and in combination with Darzalex (daratumumab). The study will compare the regimens to a standard combination therapy based on Darzalex.

Last month, EMA recommended the non-renewal of the conditional authorization of another BCMA therapy, namely GSK’s antibody-drug conjugate Blenrep (belantamab). The recommendation followed the failure of the treatment to improve progression-free survival in a confirmatory trial. GSK has asked for the recommendation to be re-examined.

EMA Notice, More

Euro Roundup: MHRA aims to accelerate approval of lowest-risk clinical trials

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