NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

RE: FWIW- My thoughts on MHRA MAA timeline:

Now that the application has finally been submitted, I guess it’s time to start forecasting how long it will take for the decision on approval. First, I think that you laid out some valid points on both sides, and at this point, it’s really anyone’s guess. I personally agree with you that you are “probably too optimistic,” but I think that many on this board would probably agree with your forecast. I lean more to the optimistic side, but tend to be more realistic.

While there is precedent for very rapid regulatory approvals for COVID-19 treatments, that was during a national health emergency, which most would probably argue that Glioblastoma is not. It seems very unlikely to me that DCVax would receive such a rapid approval, considering the application is for novel cell therapy, which has a novel mechanism of action, multiple unique co-developed assays, non-traditional supply chain, which are just some of the many unique and complex issues on the manufacturing side of this massive application that assessors must evaluate, and there are multiple unconventional issues on the clinical side as well.

It’s not a secret that the MHRA has been backlogged since Brexit, which occurred in January 2020, right before Covid shut everything down, resources were diverted, and Covid treatments were prioritized. Like many other businesses post Covid, the MHRA’s resources have remained constrained, and proper staffing has been a problem.

To address this issue, starting last spring, new assessors were hired and trained, and apparently now, staffing levels are finally where they need to be in order to clear backlogs for both new clinical trial applications, as well as marketing applications. Additionally, to speed the assessment process, the MHRA has also focused on improving the quality of the marketing applications themselves, by providing assistance during the pre-submission phase, to ensure that all of the necessary assessment criteria is well understood, and is organized correctly.

The MHRA will prioritize high quality applications for medicines that address an area of unmet need, and the awareness in the UK about the lack of treatment options for Glioblastoma, has been raised by the deaths of high-profile politicians and public figures, so it seems likely that Northwest Bio’s application will receive priority. If it does, given the MHRA’s backlog, but desire to return to established regulatory timelines, and given that Northwest Bio took extra time to ensure the high quality of their application, I think it may be possible for Northwest Bio to receive a rapid decision within the established timeline of 210 days. (150-day assessment with <60-day clock off period) I personally anticipate an approval in the UK in the 3rd quarter, but I remain optimistic that it’s possible to receive an approval even earlier, in the 2nd quarter.

Several articles were published last summer about the delays in the UK, but I will just highlight some parts of one:

Regulatory Shortages and Delays - Navigating the MHRA's Post-Brexit Transition
on Tuesday, 18 July 2023.
Alice Mennell

The regulatory shortages and delays faced by the Medicines and Healthcare products Regulatory Agency (MHRA) in the aftermath of Brexit have raised concerns in the pharmaceutical industry regarding the timely launch of products in the UK market.

This article explores key takeaways from a recent session at the 2023 PING Conference, where Dr Shirley Hopper (Deputy Director, Innovative Medicines, HQA at the MHRA) and Dianne Lee (Chair, Hertfordshire LEP Life Sciences Industry Panel; and CEO, DLRC) discussed these challenges and highlighted the MHRA's efforts in addressing them, as well as the actions industry players could take to facilitate this endeavour. The session also touched upon the role of artificial intelligence (AI) and the international recognition framework in improving efficiency and global harmonisation.

Tackling the Delays
Dr Hopper emphasised the MHRA's dedication to improving patient health and access to effective medicines despite post-Brexit challenges. The discussion revealed important insights into the regulatory delays.

To address delays in licensing products, the MHRA is actively boosting recruitment and training of assessors while enhancing the capabilities and expertise of existing staff. These measures aim to clear the backlog, particularly in the area of population health, where most of the backlog currently sits.

In addition, the MHRA has begun to prioritise clearing the backlog, rather than reviewing applications on a first-come, first-served basis. The agency is also working on providing greater predictability by publishing performance data on different application types.

The MHRA is continuing to prioritise applications based on public health needs and supply issues. During the pandemic, expedited procedures were implemented, prioritising new active substances, first generics, and first biosimilars to support the NHS. Timelines for established medicines are expected to return to normality by 2024, with clinical trials potentially resolving even earlier.

https://www.vwv.co.uk/news-and-events/blog/pharma-life-sciences-law/regulatory-shortages-delays-brexit

And here’s the latest performance update from the MHRA, which indicates that some of the backlogs are clearing, and timelines are returning to normal:

Transparency data
MHRA performance data for assessment of clinical trials and established medicines
Updated 15 December 2023

We publish routine updates to performance data for the assessment of clinical trials and established medicines within 15 days of the end of each month. This is to help applicants understand the MHRA’s timelines for decision making in relation to applications for clinical trials and marketing authorisations for established medicines and variations to existing approvals. 

Clinical trials
The latest MHRA performance data shows that clinical trials applications continue to be handled within 30 days and amendments within 35 days, i.e. meeting statutory timescales.

Since September, regulatory assessments for clinical trials have been completed in an average of 24 days for initial assessments (within the statutory timescale of 30 days) and an average of 21 days for assessments of amendments (within the statutory timescale of 35 days).

The MHRA has implemented streamlined processes to reduce the time taken to process clinical trial applications and has eliminated backlogs. We have now embedded a range of changes into our standard working practice and will build further on these changes with new legislative measures to make it easier and faster for applicants to gain approvals and to run clinical trials in the UK.

We launched a Notification Scheme for clinical trials in October 2023, which will further reduce the approval time for low-risk trials by more than 50 per cent. We encourage applicants for low risk trials which meet the criteria to submit your application via the notification scheme. You will receive confirmation within 14 days.
 More information regarding individual trial application status, is available via  [e-mail]

Established medicines
We continue to deliver accelerated improvements to timescales for the assessment of established medicines. Current timescales for regulatory decisions are within statutory timeframes in the following areas:

* Validation
* Compliance
* Type 1 A variations
* Type 1 B variations
* Reliance Applications
* ECDRP Applications

To achieve this, we have improved the application process and identified and acted on opportunities to speed up regulatory assessment without compromising patient safety, and increasing the quality of applications received, by creating clear guidance for applicants to improve right-first-time submissions.

For National applications for generic medicines our current throughput time is approximately 24 months from time of validation. We recognise this is an area we must continue to focus on to improve the speed of regulatory assessments, along with delivery of Type II variations are committed to ongoing work to clear any backlogs.
We have made improvements in our assessment process, though we ask companies to ensure that applications are correct by eliminating our most frequently seen error sources. The following three areas are where we continue to see the highest error sources in applications:

* Use of bioequivalence and inappropriate biowavers
* Specification and appropriateness of dissolution and impurities
* Requirement for Nitrosamines Assessment

Further information to support users in improving the quality of submissions to MHRA can be obtained via:  

* Updates of Module1 to provide current information
* Sharing of Major issues on applications and updates prior to assessment
* Priority list changes and increasing communication
* Clinics to answer questions and provide further support to applicants
* We have sent a letter to all companies to share information about routes of update and activities we are taking to improve throughputs

We are committed to continuing action to clear the backlogs. More staff recruited in the previous 12 months continue through their training and accreditation. We are working to define progress targets to increase proportions of applications completed within statutory timelines and will publish data on average timescales of regulatory assessments at each stage from January 2024.

https://www.gov.uk/government/publications/mhra-performance-data-for-assessment-of-clinical-trials-and-established-medicines/mhra-performance-data-for-assessment-of-clinical-trials-and-established-medicines