Under Scott Gottlieb I thought the FDA was really moving in the right direction, with his departure things seem to be headed back toward where they were. I don't know how flexible they will be in terms of accepting changes NWBO is looking to make in evaluating the Phase 3 Trial data.
I believe in Europe and elsewhere the authorities are more open to thinking for themselves about how drugs are working. If you have results showing that substantial numbers benefit from the drug, even if you failed to meet pre-established goals, I believe they will see the benefits and approvals will result.
Sadly, many highly regarded American Doctor's have moved overseas into world class hospitals where they can use drugs and techniques that are not yet approved in the U.S. Programs like 60 Minutes have reported on these facilities, where not only is the medical treatment excellent, but so is the food, and while you're recuperating you do so in world class 5 star hotels that have needed nursing and other support. The cost of treatment is lower than here, and I believe some insurance companies are starting to consider authorizing the foreign coverage.
I believe the ball is in the FDA's court, they can continue to do things as they do, and chase more Doctor's to establish foreign practices, or they can modernize they're thinking and permit drugs which clearly show benefits to be used faster. The NWBO trial has taken over a decade, that is ridiculous, and it's far from the only one to do so. The FDA needs to get inside the trials, work with the clinicians, and when they see benefits, say it's approved, not wait for further documentation. Run Phase 4's to validate what they approve for every drug, and be open to removing the approval if problems are seen, but get new products on the market for much lower trial costs, and lower prices, in a fraction of the time that's currently required.
As I understand it, NICE will go active with their considerations, as and when a marketing authorisation application (MAA) is submitted to the regulatory authority, which is the EMA, unless and until the UK leaves the EU without agreement, in which case it reverts to the MHRA.
At the same time as submitting the MAA, the company should also make submission to NICE. The submission to NICE will have much in common with the MAA submission, but will also require the company to provide data to support their view about how the treatment affords additional Quality-adjusted Life Years (QALY's), because NICE is interested in cost-effectiveness, whereas the FDA and the EMA couldn't care less.
So the submission to NICE has to include pricing proposals, and has to include a state partition analysis (basically how long you live without debilitating disease progression), so they can assess price per QALY gained. NICE will pay higher per QALY if the treatment is considered an 'end of life' treatment, which is when life expectancy under existing treatments is less than 2yrs. Arguably, DCVaxL would qualify for such a higher rate. If NICE agrees a treatment is cost-effective at a certain price and makes a recommendation to that effect, then the NHS will fund and make fully available.
I get the impression that a lot of companies make an initial pricing proposal, expecting to be knocked down, and then 'adjust' their price if necessary. Nobody will pay US drug prices...
NHS/NICE also use the NIHR body which 'horizon scans' promising new treatments, and puts them on the list for NICE to begin its consultation process. That bit has happened. But it won't go past the early consultation phase until NWBO submits an MAA, and makes a suitable submission to NICE. Then what happens is NICE do their own evidence review at the same time as the MAA is being considered, with the intention of making their recommendation almost simultaneously with the MAA approval (if indeed it is forthcoming). They did this with the two approved Car-T's, announcing their decision within days of EMA approval. (Accepting one but not the other if I recall correctly)
I guess NICE would be interested in seeing the SAP, so it might be included in the submission to NICE. NWBO will be submitting unusually long term survival data to NICE, which NICE will like. If this gets approved in Europe, then I predict NICE will agree to fund if it is priced at around £150-£170k. Occasionally if NICE want to see more long term data before giving longterm commitment to fund, there is another body called the Cancer Drug Fund, which may interim fund until NICE is happy with long term data. But our long term data will be some of the most mature that NICE will have seen. That PIM designation from a few years back sounded good but in practical terms it wasn't feasible for NWBO to pursue to the next stage. It was one of those politician devised schemes that is designed to make them look like they are doing something pro-active, when they're not really. Maybe a bit like the Cancer Moonshot? But, it did get DCVax on the radar, and NICE are standing by, to go active on this. Advent are going to move into Sawston and get a licenced manufacturing facility up and running within a year I predict. All will be set.
That's why I think they should prioritise Europe, given that the FDA, imo, have already contributed to delaying this trial, and I just don't have any faith in their objectivity or their decision-making. You've only got to look at how they created the Opioid crisis to know that they don't make rational decisions.
As to my 4 RA's. Well I wasn't seriously suggesting that the FDA wouldn't be one of the 4, and I did just pick Japan out of the air...(And I know nothing about Japanese approval systems) But behind that flippancy, I do think that they should give at least as much priority to Europe as they do to the US. Don't forget Mark Lowdell has set up his Autolomous company to devise the optimum IT system for fully accountable and cost-effective delivery of autologous medicines in the UK.