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Regulatory Focus™ > News Articles > 2019 > 10 > EU Regulatory Roundup: CHMP Questions Delay Novartis Gene Therapy Approval Timeline

EU Regulatory Roundup: CHMP Questions Delay Novartis Gene Therapy Approval Timeline

Posted 24 October 2019 | By Nick Paul Taylor 

EU Regulatory Roundup: CHMP Questions Delay Novartis Gene Therapy Approval Timeline

Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
 
CHMP Questions Delay Novartis Gene Therapy Approval Timeline
 
Tougher than expected regulatory scrutiny has delayed Novartis’ efforts to bring its spinal muscular atrophy gene therapy Zolgensma to patients in Europe. Novartis had hoped to win approval by the end of the year, but now expects the Committee for Medicinal Products for Human Use (CHMP) to deliver its opinion in the first quarter of 2020.
 
The delay stems from CHMP’s scrutiny of the manufacturing portion of the filing.
 
“[There] were an extensive set of questions with respect to the manufacturing in CMC. We've now submitted those responses, but we need to continue to work through these responses with EMA to get to the final positive opinion,” Novartis CEO Vasant Narasimhan said on a call with investors.
 
Zolgensma is the focus of a data manipulation scandal, but Novartis said the delay is not specifically related that issue. Rather, the extra time is needed to work through questions about manufacturing and perform additional inspections of Novartis’ production facilities.
 
The delay comes months after CHMP switched Zolgensma from its accelerated to standard review programs, adding 60 days to the time it has to assess the submission for approval.
 
Call Transcript, Reuters
 
EMA Sketches Plan for Supporting Alternatives to Antimicrobials
 
The Committee for Medicinal Products for Veterinary Use (CVMP) has published a reflection paper on ways to promote authorization of alternatives to antimicrobials. CVMP used the reflection paper to discuss existing barriers to the authorization of alternatives and ways to overcome them.
 
Given the focus on antimicrobial resistance in the incoming veterinary regulation and other European Union documents, CVMP sees the stimulation of the development of alternative ways to prevent and treat bacterial infections as a key part of its agenda over the years to come. That led CVMP, one of the European Medicines Agency’s (EMA) committees, to identify gaps that could stymie development and propose ways to improve the situation.
 
CVMP groups the gaps into three categories: gaps in the EU regulatory framework, gaps in support to developers and applicants and gaps in strategic collaboration and communication with stakeholders.
 
Some of the gaps can be addressed quickly and with minimal additional investment or through the use of existing initiatives. For example, CVMP thinks a definition for “alternatives to antimicrobials” may drive regulatory harmonization in the European Union and around the world, thereby making it easier for companies to get products to market. CVMP sees that as a short-term action with minimal resource impact.
 
It will be harder to address some of the other gaps identified by CVMP. The medium- to long-term projects identified in the analysis include the creation of regulatory requirements for a number of emerging therapeutic modalities, such as peptides that kill bacteria in a way distinct from classical antibiotics and “gene editing technology presented as medicinal products.”
 
CVMP thinks gene editing technology, such as CRISPR-Cas9, may be able to reduce antimicrobial use by targeting bacterial pathogens or restoring the efficacy of existing products in resistant strains. However, those goals are some way off, with CVMP noting that there is a “need to improve knowledge in regulatory domain of potential use of gene editing technology.”
 
The reflection paper also discusses the possibility of using financial incentives to encourage the development of alternatives to antimicrobials. CVMP notes that the industry has raised the possibility of such “pull” incentives. EMA remains unconvinced, though, with CVMP expressing the view that “financial or other procedural, regulatory incentives, over and above those already in place, are not the most significant factor reducing interest in developing.”
 
It may be hard for EMA to provide additional incentives even if it wanted to. CVMP notes that there is “no clear legal basis on which EMA could systematically provide such incentives in the veterinary domain under the current legal framework.”
 
CVMP is accepting feedback on the reflection paper until the end of April.
 
Reflection Paper
 
Ireland’s HPRA Revises Advice on end of Trial Declarations
 
Ireland’s Health Products Regulatory Authority (HPRA) has revised its advice on end of trial declarations. The updated guide to clinical trial applications explains what sponsors need to do when the Irish and global portions of studies end.
 
In revising the guide, HPRA has strengthened the language about the need to tell HPRA if the Irish portion of a multinational clinical trial ends before the global study is complete. The notification of the end of the clinical trial in Ireland serves to free the sponsor for local submission requirements and development safety update reports.
 
The revised guide also features a new paragraph on what sponsors should do when the global end of the trial happens. HPRA is advising sponsors to submit the EU Declaration of the End of Trial form. If the Irish and global trial end dates coincide, the sponsor should only submit one notification.
 
HPRA made the changes alongside a few very minor revisions to other parts of the guide.
 
HPRA Guide
 
Swissmedic Provides More Details on Filing to Renew Authorizations
 
The Swiss Agency for Therapeutic Products (Swissmedic) has provided further details about applying to renew authorizations. Swissmedic’s additional information covers when companies should file and what documents they should include.
 
Swissmedic adopted the first version of the renewal of authorization form earlier this year and went on to tweak it over the following months. The latest update adds information to a “Notes” section of the form that offers advice on the renewal process and questions about the implementation of label and product information requirements.
 
The notes section now states that applications “should be submitted together with the required documents and, where applicable, the discontinuation decision 1 year at the earliest but not later than 6 months before expiry of the authorization.”
 
Elsewhere in the document, Swissmedic has added two sections that pose the same question, namely have the labeling and product information requirements in accordance with the revised TPLRO already been implemented? One of the sections poses the question to companies working with human medicinal products, while the other addresses the veterinary industry.
 
Swissmedic Forms
 
MHRA Appoints Interim Directors of Devices and Pharmacovigilance
 
The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has appointed two interim directors. Graeme Tunbridge stepped up to the position of interim director of devices and Sarah Branch took up the same position at the department of vigilance and risk management of medicines.
 
MHRA promoted Tunbridge, formerly the group manager for devices regulatory affairs at the agency, to fill the vacancy created by the retirement of John Wilkinson. Tunbridge first joined MHRA in 2011 to lead the UK government’s input into negotiations about changes to the EU device rules.
 
The promotion of Branch was originally disclosed last month when June Raine took over as interim CEO of MHRA. Raine’s promotion created a vacancy at the head of the department of vigilance and risk management of medicines. Branch will fill that vacancy, at least while Raine is serving as interim CEO.
 
MHRA Notice, More
 
Other News:
 
Pfizer is recalling batches of docetaxel from the UK after routine stability testing found levels of a known impurity, 10-oxo-docetaxel, may rise to above the accepted threshold by the end of the drug’s shelf life. The recall, details of which were shared by MHRA, affects two batches of the cancer drug sold in the UK. MHRA Notice

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