Conditional Approval For DCVax-L?
Thoughts About What This Would Mean For Northwest Biotherapeutics (NWBO)
“I said I just dropped in to see what condition my condition was in.”
Having past the 900 day mark and lumbering towards 2 1/2 years since submission, the Marketing Authorization Application (MAA) to the Medicines and Healthcare products Regulatory Agency (MHRA) for DCVax-L by NWBO remains in a Kafkaesque limbo. The actions of the MHRA, or rather inaction, make it seem like patients, NWBO and its shareholders are lost in an indifferent, impenetrable and inescapable maze created by unaccountable bureaucrats. But one day, the MHRA will have to announce a decision, and one of the possibilities is that aside from an outright approval or rejection, the MHRA will grant conditional approval. What could be the ramifications and impact of such an outcome?
Investors too are wandering around this opaque maze and have with no special knowledge about the MHRA decision, and this article is pure speculation. However, given the length of time of the review process, it’s our view that an outright rejection of the MAA is unlikely. If there were critical flaws with the application, they would be apparent by now. If there were concerns about the treatment itself then the MHRA would have stopped compassionate care use under the specials program. As DCVax-L has proven efficacy, an unparalleled safety profile, approval, either outright or conditional, is probable. While the former decision would be straightforward, the latter could lead to possible misinterpretation. Those who have spent years attacking NWBO would spin such a result in a negative way to try and damage the stock price and company. In our view, a conditional approval is not materially different from outright approval. Let’s have a look why we believe this to be the case.
The first question is why there could be conditions placed on the approval. There could be valid empirical scientific reasons such as valid questions about the composition of the external control arm used to measure efficacy or the cross-over nature of the trial where all patients were given access to DCVax-L. While Tthese seem to be the most likely questions or concerns, but there could be other causes for the delay. We also wonder if those nefarious forcesd arrayed against NWBO have tried to scuttle the approval process. With a likely rumored naked short position in excess of a billion shares, approval would deal a blow to those holding these shorts positions. With so much money at stake, if these people can’t stop full approval will they try to make it conditional? Regardless, So how would might a conditional approval work?
The official MHRA term for this type of approval would be a is Conditional Marketing Approval (CMA). A company receiving CMA has obligations to fulfill the conditions applied to the approval. Per Grok:
“MHRA conditional marketing authorizations (CMAs) include case-specific “specific obligations” (post-authorization conditions) that the company must fulfill, usually within defined timelines. These are legally binding, reviewed annually (as the CMA lasts 1 year and is renewable), and focus on confirming or strengthening the benefit-risk profile through more data. Failure to meet them can lead to suspension or revocation.”
The MHRA has granted CMAs to several other treatments with differing obligations. Again, per Grok (in Italics with our response in Bold):
Common Themes in MHRA CMA Conditions
Completion of ongoing trials with mature data (e.g., longer follow-up for survival endpoints).
Unlikely: The last patient in the DCVax-L trial was enrolled in November of 2015 so it is our belief that NWBO has likely provided the 10-year trial information to the MHRA.
New post-approval studies (interventional or real-world/non-interventional registries).
Possible: Since the trial was designed and completed, it has been found that patient response is far impressively higher when DCVax-L is used in combinations with adjuvants and/or check-point inhibitors. Perhaps the MHRA will require this these combinations, and the company has been busy setting up such a study. But there is an important distinction here as this would not necessarily necessitate a new trial. If DCVax-L was going to be used by doctors this way in this manner, it would be a matter of record keeping. With the UCLA combination trial with Keytruda having a primary completion date of Aug. 2026, maybe this data could be used to support at least one of these combinations?
Enhanced safety/pharmacovigilance monitoring.
Unlikely: The safety profile of DCVax-L is excellent with only minor side effects. However, this might be required if a study on a combination treatment was required.
Manufacturing/quality data (especially relevant for autologous/personalized therapies).
Possible: The company currently uses a manual manufacturing process but will transition to an automated one using the Flaskworks designed Eden system. The MHRA may desire surveillance of the new system and require detailed analysis of it.
Subgroup analyses or data in specific populations.
Possible: There are several subgroups such as methylated vs. unmethylated and newly diagnosed vs. recurrent though why the MHRA would focus on this issue subgroups is not clear.
Furthermore, Grok says this about CMAs:
Conditions are tailored to the remaining uncertainties at approval (e.g., single-arm trials, immature survival data, or manufacturing for cell therapies). Once fulfilled satisfactorily, the CMA can convert to a standard/full marketing authorization.
There are several pros and cons of a CMA. The biggest negative is that it would impose additional costs on the company to the extent of which depends upon of what the MHRA might required. A multi-year study could cost several millions and divert the attention of a slim management staff. The other negative is, as mentioned above earlier, it a conditional approval might would provide misleading fodder for the nay-sayers, shorts and paid shills who continuously attack NWBO.
However, it our belief that the pros of a CMA far outweigh the cons. It would allow NWBO to market DCVax-L and become a revenue generating company. A CMA allows NICE, the U.K. government body responsible for drug payments, to pay for treatment. A stream of NICE guaranteed revenue would likely lead to a re-rating of the stock and allow for an uplisting of the stock. This validation of DCVax-L would and uplisting would attract institutional investors. Also, a CMA would be the first positive regulatory acknowledgment of DCVax-L which paves the way for other regulatory agencies like the FDA, Health Canada and the EU to do so. Lastly, any additional information gathered for the CMA can be used by the company in other applications.
While full approval would be a doubleplus good outcome, a CMA would still be a good result for the company and don’t be swayed by the spin of the negative nattering nabobs of NWBO who will try to get you to believe otherwise.
As we wait for word from the MHRA let’s drop in on someone else’s condition, namely that of Jeff Lebowski.