Circling back to this post. Today is the 111th day since the Nov 27/28th CHM meeting (where we now know for absolute certainty that DCVax was discussed). This means DCVax has now gone beyond Illuccix, the prostate cancer diagnostic radioisotope, which previously held the record for the longest time an MAA (under this National Assessment pathway) took to go from the CHM meeting to a Full Approval.
As a reminder, the next available example of an MAA under this same pathway that took longer is Aucatzyl, the autologous CAR-T therapy, which took 154 days to go from its CHM discussion to a Conditional Marketing Authorisation (CMA) announcement.
So, are we now moving into CMA territory?
Possibly. But given the massive 518-day abyss between CHM meetings, it is clear that the DCVax assessment is in a league of its own regarding complexity. That same level of complexity likely applies to the final document preparations (Risk Management Plans, label negotiations, post-approval obligations), which is drawing out this post-CHM timeframe longer than previous assessments. As many have hypothesised, the MHRA might also be waiting to publish specific guidance first before making the official announcement (that said, in theory they cannot simply wait past their own statutory clock so this argument looses weight IMO)
As of yesterday, we received clear confirmation from UK Parliament that the assessment is indeed ongoing, which definitively rules out any fears/ rumours of application rejection or withdrawal. In that same reply, Labour MP Dr. Zubir Ahmed stated: "The MHRA conducts a rigorous, evidence-based scientific review of all applications for marketing authorisation and assesses them against statutory timelines." If we are indeed still operating within the MHRA's strict statutory timelines, it indicates the agency has been extremely flexible and forgiving with their clock-off allowances for NWBO. LP hinted at this during the ASM when she intimated how accommodating the MHRA has been.
Here is what I personally believe happened during that 518-day abyss between CHM meetings:
I believe the MHRA mandated that LP had to fully integrate Advent within the company for the assessment to proceed. By bringing long-term operational control of the manufacturing in-house instead of outsourcing to a CDMO (even if owned by the CEO, the MHRA Quality Assessors and ATMP Inspectors don't care about personal ownership, only corporate control), the CMC Risk Management maths finally added up in favour of a continued assessment.
To achieve this, I believe the MHRA granted the company an exceptional ~6 month extension to their clock-off period to complete the acquisition and reconfigure the manufacturing risk management framework to align with MHRA requirements. The timeline makes perfect sense:
August 28th: Company announced the agreement to acquire Advent (likely taking months of prior legal prep).
October 24th: Deal closed.
November 28th: 2nd CHM Meeting. Major objection(s) cleared.
December 15th: Advent MIA Certificates updated (just 18 days later) to reflect the change of ownership variation.
So where does this leave us now?
The theoretical total amount of clock-off time a Sponsor can take is 12 months (6 + 3 + 3) across 3 rounds of RFIs. Today, we are on Day 818 since the application, or 741 days since validation (the real Clock-On Day 0). If we have remained within the 210-Day statutory clock-on limits of the HMR 2012 Schedule 11 framework (as Dr. Ahmed's answer implies), an exceptional extension was undoubtedly granted.
If we assume the MHRA is not delayed at all on their end and the 210-day clock is running normally, but a ~6-month exceptional extension was granted to allow LP to acquire Advent, here is where we stand based on the MHRA’s Statutory Timetable:
- The 2nd CHM meeting occurs at Day 150 of the regulatory clock.
- This leaves the MHRA with exactly 60 statutory clock-on days left to reach the final Day 210 decision.
- Following the 2nd CHM, to resolve outstanding minor issues (like finalising the label, post-acquisition facility paperwork, or the Risk Management Plan), the standard maximum clock-off allowance for NWBO is 90 days.
- Combined (60 MHRA days + 90 NWBO days), the maximum calendar time allowed between the 2nd CHM and a final Day-210 decision is 150 calendar days.
So, given we are on calendar day 111 today since the 2nd CHM, I estimate the maximum amount of calendar days remaining is 39, which takes us out to April 27th. If you add the allowable built-in 3-day administrative "restart" buffer, we land right around April 30th / May 1st.
(Remember Aucatzyl took 154 days, which is essentially the same exact maximum* CHM to Announcement timeframe 150 + buffer days).
This means that right now, the MHRA should be wrapping up final minor compliance checks, negotiating the final Summary of Product Characteristics (SmPC) and labelling, and preparing the final Assessment Report for the Day 210 decision. As utterly excruciating has it has been, the end really should now finally be in sight!
GLTA
*I realise at this juncture some folk might remember the other two examples I gave in my previous post, which were two very similar treatments for Alzheimer’s Disease (Kisunla & Leqembi), which took 180 & 182 days to go from CHM to their respective CMAs, however these were highly exceptional circumstances in that they both had significant safety red flags with extremely complicated approval conditions for restricted populations and mandatory patient testing requirements to identify eligibility.
Bullish
AI
