$NWBO #DCVax #DCVaxForBraelyn 𝗧𝗛𝗘 𝗦𝗘𝗖𝗢𝗡𝗗 𝗖𝗟𝗢𝗖𝗞 𝗪𝗵𝗮𝘁 𝗶𝗳 𝘄𝗲 𝗵𝗮𝘃𝗲 𝗯𝗲𝗲𝗻 𝗺𝗲𝗮𝘀𝘂𝗿𝗶𝗻𝗴 𝘁𝗵𝗲 𝗗𝗖𝗩𝗮𝘅-𝗟 “𝗱𝗲𝗹𝗮𝘆” 𝗮𝗴𝗮𝗶𝗻𝘀𝘁 𝘁𝗵𝗲 𝘄𝗿𝗼𝗻𝗴 𝗳𝗶𝗻𝗶𝘀𝗵 𝗹𝗶𝗻𝗲? DCVax-L’s UK Marketing Authorisation Application was submitted on December 20, 2023. Today marks 1,016 calendar days. The obvious question has always been: “Why is MHRA taking so long?” I think there may be a better one. 𝗪𝗵𝗮𝘁 𝗶𝗳 𝗮 𝘀𝗲𝗰𝗼𝗻𝗱 𝗰𝗹𝗼𝗰𝗸 𝗵𝗮𝘀 𝗯𝗲𝗲𝗻 𝗿𝘂𝗻𝗻𝗶𝗻𝗴 𝗯𝗲𝘀𝗶𝗱𝗲 𝘁𝗵𝗲 𝗳𝗶𝗿𝘀𝘁? Under the traditional UK model, the process was largely sequential: 𝗠𝗛𝗥𝗔 𝗿𝗲𝘃𝗶𝗲𝘄 ↓ 𝗠𝗮𝗿𝗸𝗲𝘁𝗶𝗻𝗴 𝗮𝘂𝘁𝗵𝗼𝗿𝗶𝘀𝗮𝘁𝗶𝗼𝗻 ↓ 𝗡𝗜𝗖𝗘 𝗮𝗽𝗽𝗿𝗮𝗶𝘀𝗮𝗹 ↓ 𝗡𝗜𝗖𝗘 𝗴𝘂𝗶𝗱𝗮𝗻𝗰𝗲 ↓ 𝗡𝗛𝗦 𝗳𝘂𝗻𝗱𝗶𝗻𝗴 𝗮𝗻𝗱 𝗮𝗰𝗰𝗲𝘀𝘀 Approval was never the same thing as access. NICE says there has typically been about a 90-day gap between MHRA marketing authorisation and NICE guidance. The new MHRA-NICE Aligned Pathway is specifically designed to remove that gap. Instead of running the clocks one after another, Britain can now run them in parallel. 𝗠𝗛𝗥𝗔 𝗿𝗲𝘃𝗶𝗲𝘄 ↕ 𝗡𝗜𝗖𝗘 𝗮𝗽𝗽𝗿𝗮𝗶𝘀𝗮𝗹 ↓ 𝗟𝗶𝗰𝗲𝗻𝗰𝗲 + 𝗡𝗜𝗖𝗘 𝗴𝘂𝗶𝗱𝗮𝗻𝗰𝗲 ↓ 𝗔 𝘀𝗵𝗼𝗿𝘁𝗲𝗿 𝗿𝗼𝗮𝗱 𝘁𝗼 𝗳𝘂𝗻𝗱𝗲𝗱 𝗡𝗛𝗦 𝗮𝗰𝗰𝗲𝘀𝘀 NICE can now hold appraisal committee meetings before marketing authorisation. It can publish draft guidance before authorisation. It can even complete final draft guidance before MHRA makes its decision, with the recommendation conditional upon the licence ultimately being granted. For medicines that remain on schedule, the stated objective is simultaneous publication of the MHRA licence and NICE guidance. The government estimates this can remove 3 to 6 months from the journey to patients. 𝗕𝘂𝘁 𝗵𝗲𝗿𝗲 𝗶𝘀 𝘄𝗵𝗲𝗿𝗲 𝗗𝗖𝗩𝗮𝘅-𝗟 𝗯𝗲𝗰𝗼𝗺𝗲𝘀 𝗽𝗮𝗿𝘁𝗶𝗰𝘂𝗹𝗮𝗿𝗹𝘆 𝗶𝗻𝘁𝗲𝗿𝗲𝘀𝘁𝗶𝗻𝗴. The second clock did not suddenly appear in 2026. 𝗕𝘆 𝗦𝗲𝗽𝘁𝗲𝗺𝗯𝗲𝗿 𝟮𝟬𝟮𝟰, 𝗡𝗼𝗿𝘁𝗵𝘄𝗲𝘀𝘁 𝗕𝗶𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 𝘄𝗮𝘀 𝗮𝗹𝗿𝗲𝗮𝗱𝘆 𝘄𝗼𝗿𝗸𝗶𝗻𝗴 𝗼𝗻 𝗿𝗲𝗶𝗺𝗯𝘂𝗿𝘀𝗲𝗺𝗲𝗻𝘁. The company disclosed that it had selected specialized reimbursement consultants, executed contracts, and begun the first stage of the process. That work included health economics and outcomes analyses, analysis of the clinical landscape, engagement with experts and stakeholders, and other preparations necessary for reimbursement review. That is not theory. That is Northwest telling us that while one process was occurring at MHRA, another process was already being built around what happens 𝗮𝗳𝘁𝗲𝗿 regulatory approval. And there was already infrastructure connecting those worlds. MHRA’s Operational Information Sharing system allows an applicant, with consent, to let MHRA share administrative information with NICE and NHS England, including the regulatory route, submission date, estimated MHRA decision date, and ultimately the actual decision. The stated purpose is to allow the health system to prepare its own processes more efficiently and reduce avoidable delays in patient access. We do not know publicly whether Northwest provided that consent. But the channel exists. And DCVax-L was not arriving at NICE as a new product. It already had 𝗜𝗗𝟴𝟯𝟲. NICE had referred the topic years earlier, conducted scope work, consulted stakeholders, and invited the company into the appraisal process. In fact, in the 2018 ID836 scope documents, NICE was already stating that it aimed to publish guidance on cancer drugs within 90 days of marketing authorisation. So the regulatory and reimbursement tracks around DCVax-L have a much longer history than the current aligned pathway. Then the public chronology becomes very interesting. 𝗔𝗽𝗿𝗶𝗹 𝟮𝟴, 𝟮𝟬𝟮𝟱. The UK government tells Parliament that NICE aims, wherever possible, to issue recommendations close to the time of MHRA licensing. Then it confirms something specific to DCVax-L: NICE is already in discussions with the manufacturer about a potential appraisal, subject to licensing. That is important. It means the NICE clock was publicly visible months before the formal aligned pathway opened. 𝗢𝗰𝘁𝗼𝗯𝗲𝗿 𝟭𝟬, 𝟮𝟬𝟮𝟱. MHRA and NICE open the aligned pathway to early adopters six months ahead of schedule. And they specifically invite companies whose products already have NICE technology appraisals scheduled to contact NICE if their medicine may be suitable. DCVax-L already had exactly that kind of NICE history through ID836. The new system offers priority NICE scheduling and coordinates licensing and value assessment so the decisions can be published together. This does not automatically move an existing product onto the pathway. The company has to participate. We do not have public proof that Northwest did. But DCVax-L clearly sits inside the category NICE was actively seeking. 𝗗𝗲𝗰𝗲𝗺𝗯𝗲𝗿 𝟴, 𝟮𝟬𝟮𝟱. The government makes another unusually specific statement about DCVax-L: The application “is not affected by any historical backlogs.” Then it again confirms that NICE is in discussions with Northwest Biotherapeutics about a potential appraisal subject to licensing. Whatever is consuming the time, the UK government has therefore specifically told us what it is not. It is not simply the old MHRA backlog. 𝗠𝗮𝗿𝗰𝗵 𝟭𝟴, 𝟮𝟬𝟮𝟲. The government repeats that DCVax-L remains under MHRA assessment and again states that NICE aims to issue recommendations close to licensing and is discussing a potential DCVax-L appraisal with Northwest. 𝗔𝗽𝗿𝗶𝗹 𝟮𝟬𝟮𝟲. The aligned pathway becomes fully operational. At essentially the same time, another variable changes. NICE raises the standard cost-effectiveness range from £20,000 to £30,000 per QALY to £25,000 to £35,000 per QALY. And critically, NICE says the new thresholds apply not just to future appraisals, but also to technology appraisals already underway. For a personalized living-cell therapy with an unusual upfront manufacturing cost structure, that change is potentially material. It does not guarantee a favorable NICE decision. But it unquestionably changes the economic framework within which an appraisal occurring today would be judged. 𝗝𝘂𝗹𝘆 𝟮𝟬𝟮𝟲. Northwest presents new individual-patient-level survival analyses at BNOS using propensity score matching and inverse probability weighting against external randomized-trial controls. The analyses were performed by independent statisticians and produced results broadly consistent across multiple comparator datasets and analytical approaches. Those methods are also highly relevant to health technology assessment because they address one of the central problems with external controls: balancing measured confounders between treated patients and comparison populations. That does not establish that the BNOS analyses were created for NICE. But the same evidence can plainly matter to both clocks. 𝗦𝗲𝗽𝘁𝗲𝗺𝗯𝗲𝗿 𝟮𝟴, 𝟮𝟬𝟮𝟲. I wrote directly to MHRA asking about the extraordinarily long DCVax-L process. MHRA responded that it is: “working actively on this application” and is: “progressing this application as rapidly as possible and in collaboration with the company.” MHRA also specifically directed me to NICE’s DCVax-L appraisal, ID836. That does not prove DCVax-L is on the aligned pathway. But it establishes something important at the very end of this timeline. 𝗧𝗵𝗶𝘀 𝗶𝘀 𝗻𝗼𝘁 𝗮 𝗱𝗲𝗮𝗱 𝗮𝗽𝗽𝗹𝗶𝗰𝗮𝘁𝗶𝗼𝗻 𝘀𝗶𝘁𝘁𝗶𝗻𝗴 𝗶𝗻 𝗮 𝗾𝘂𝗲𝘂𝗲. MHRA says it is actively working on it, rapidly, and in collaboration with Northwest. Two days later, on 𝗦𝗲𝗽𝘁𝗲𝗺𝗯𝗲𝗿 𝟯𝟬, NICE published its latest report on the aligned pathway. NICE disclosed that 90 topics across 49 therapeutic areas have now been scheduled, including products from both multinational companies and smaller and medium-sized enterprises. The names are not disclosed publicly. MHRA and NICE aligned pathway- how it's working in practice And this is perhaps the most important structural fact of all. NICE now says openly that it works with MHRA so that final guidance can be published at the same time as marketing authorisation when companies can meet the required timings. Companies are asked to keep UK PharmaScan current, update both organizations on regulatory plans, and permit operational and planning information to be shared between NICE and MHRA. That is not two agencies independently happening to finish around the same time. 𝗧𝗵𝗮𝘁 𝗶𝘀 𝗮 𝘀𝘆𝘀𝘁𝗲𝗺 𝗯𝘂𝗶𝗹𝘁 𝘁𝗼 𝘀𝘆𝗻𝗰𝗵𝗿𝗼𝗻𝗶𝘇𝗲 𝘁𝘄𝗼 𝗰𝗹𝗼𝗰𝗸𝘀. And that brings me to the thesis. 𝗧𝗵𝗲 𝗠𝗛𝗥𝗔-𝗡𝗜𝗖𝗘 𝗔𝗹𝗶𝗴𝗻𝗲𝗱 𝗣𝗮𝘁𝗵𝘄𝗮𝘆 𝗱𝗶𝗱 𝗻𝗼𝘁 𝗰𝗮𝘂𝘀𝗲 𝘁𝗵𝗲 𝟭,𝟬𝟭𝟲-𝗱𝗮𝘆 𝗗𝗖𝗩𝗮𝘅-𝗟 𝗿𝗲𝘃𝗶𝗲𝘄. It could not have. The application had already been under review for nearly two years when the early-adopter phase began. And I have found no evidence that MHRA completed its scientific review and deliberately placed an otherwise-ready licence on a shelf waiting for NICE. That is not how the aligned pathway is designed. 𝗕𝘂𝘁 𝘁𝗵𝗮𝘁 𝗺𝗮𝘆 𝗯𝗲 𝘁𝗵𝗲 𝘄𝗿𝗼𝗻𝗴 𝘄𝗮𝘆 𝘁𝗼 𝘁𝗵𝗶𝗻𝗸 𝗮𝗯𝗼𝘂𝘁 𝘁𝗵𝗲 𝗱𝗲𝗹𝗮𝘆. The more interesting possibility is that the value of the remaining time changed. If NICE appraisal preparation, health-economic work, reimbursement planning, regulatory information sharing, manufacturing readiness, and NHS access planning are occurring during the MHRA review, then every additional calendar month before the visible licensing decision is not necessarily another month added to the ultimate patient-access timeline. Some of that work is time that the old system would have forced everyone to spend 𝗮𝗳𝘁𝗲𝗿 approval. That is why simply counting days to an MHRA announcement may now tell only half the story. 𝗧𝘄𝗼 𝗰𝗹𝗼𝗰𝗸𝘀. 𝗦𝗮𝗺𝗲 𝗰𝗮𝗹𝗲𝗻𝗱𝗮𝗿. And for DCVax-L, this distinction could matter far more than it would for an ordinary pill. Northwest itself says DCVax-L is a personalized living-cell product with substantial manufacturing costs incurred upfront, specialized distribution requirements, and potentially complex reimbursement arrangements. The company explicitly warns that obtaining workable reimbursement will be essential to commercialization. For a therapy like this, a licence alone solves only part of the problem. The real finish line is not: 𝗖𝗔𝗡 𝗪𝗘 𝗦𝗘𝗟𝗟 𝗜𝗧? It is: 𝗖𝗔𝗡 𝗧𝗛𝗘 𝗡𝗛𝗦 𝗣𝗔𝗬 𝗙𝗢𝗥 𝗜𝗧, 𝗖𝗢𝗠𝗠𝗜𝗦𝗦𝗜𝗢𝗡 𝗜𝗧, 𝗔𝗡𝗗 𝗗𝗘𝗟𝗜𝗩𝗘𝗥 𝗜𝗧? Because once NICE recommends a medicine, the NHS is normally legally required to fund it within three months of final guidance. So compare the two outcomes: 𝗢𝗟𝗗 𝗙𝗜𝗡𝗜𝗦𝗛 Licence ↓ NICE appraisal ↓ Guidance ↓ Funding 𝗡𝗘𝗪 𝗙𝗜𝗡𝗜𝗦𝗛 Licence + NICE guidance ↓ Funding That is a very different endpoint. 𝗡𝗼𝘁 𝗷𝘂𝘀𝘁 𝗽𝗲𝗿𝗺𝗶𝘀𝘀𝗶𝗼𝗻 𝘁𝗼 𝘀𝗲𝗹𝗹. 𝗔 𝗽𝗮𝘁𝗵 𝘁𝗼 𝗯𝗲 𝗽𝗮𝗶𝗱. 𝗡𝗼𝘁 𝗷𝘂𝘀𝘁 𝗮𝗽𝗽𝗿𝗼𝘃𝗮𝗹. 𝗔𝗰𝗰𝗲𝘀𝘀. 𝗛𝗢𝗪 𝗧𝗢 𝗧𝗘𝗦𝗧 𝗧𝗛𝗘 𝗧𝗛𝗘𝗦𝗜𝗦 This remains a hypothesis. I cannot find public evidence proving that DCVax-L is one of the 90 topics scheduled through the aligned pathway. An old NICE appraisal does not automatically migrate into the new pathway. Northwest would have had to engage with the process. And NICE explicitly acknowledges that some complex products may use alternate scheduling, with committee consideration occurring only after marketing authorisation. So there are two versions. 𝗧𝗛𝗘 𝗦𝗧𝗥𝗢𝗡𝗚 𝗩𝗘𝗥𝗦𝗜𝗢𝗡 DCVax-L is formally proceeding through aligned scheduling, and NICE activity becomes visible before MHRA authorisation, potentially allowing NICE guidance to land with the licence. 𝗧𝗛𝗘 𝗪𝗘𝗔𝗞𝗘𝗥 𝗩𝗘𝗥𝗦𝗜𝗢𝗡 The licence arrives first, but NICE follows unusually quickly because substantial appraisal and reimbursement preparation has already occurred behind it. Either way, the place to watch is: 𝗜𝗗𝟴𝟯𝟲. It remains listed by NICE as “In development” with publication timing TBC. If substantive NICE activity appears before MHRA approval, the strong version becomes much more compelling. If MHRA approves DCVax-L and ID836 then remains dormant for months, this thesis loses much of its force. But after following the evidence from the company, Parliament, MHRA and NICE, I no longer think the most revealing question is: “Why has MHRA taken 1,016 days?” I think it is this: 𝗛𝗢𝗪 𝗠𝗨𝗖𝗛 𝗢𝗙 𝗪𝗛𝗔𝗧 𝗖𝗢𝗠𝗘𝗦 𝗔𝗙𝗧𝗘𝗥 𝗔𝗣𝗣𝗥𝗢𝗩𝗔𝗟 𝗛𝗔𝗦 𝗔𝗟𝗥𝗘𝗔𝗗𝗬 𝗛𝗔𝗣𝗣𝗘𝗡𝗘𝗗? 𝗧𝗵𝗮𝘁 𝗶𝘀 𝘁𝗵𝗲 𝘀𝗲𝗰𝗼𝗻𝗱 𝗰𝗹𝗼𝗰𝗸. Long $NWBO. 𝗔 𝗵𝘆𝗽𝗼𝘁𝗵𝗲𝘀𝗶𝘀. 𝗡𝗼𝘁 𝗮 𝗽𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝗼𝗻.