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This is both yours and FeMike’s talking points, and your comment below is simply nonexistent. It is a fiction. You made it up.
Negotiated with prerequisite DCVAXL approved in the UK.
Again. Linda knows the difference between
Maa “cemented” versus approval first.
Again, look at the history. They didn’t forgo the last planned combos because DCVax-l hadn’t reached an approval level yet beyond the compassionate program. They didn’t enter the announced but scuttled combo trials (years ago) because they weren’t financially beneficial to maintain the programs.
This is a powerful technology that NWBO has gathered eight to fifteen years of patient level data. The data has exclusivity. The biologic has exclusivity. These post submission intervals are typically when negotiations, that have been ongoing for over a year, normally get consummated.
Senti thinks she’s right that the submission has been validated and is immaterial because submission is receipt which is validation — according to her. If accurate, where is the ASM to discuss next steps aside from approval process? Two other posters state Dave won’t say if (Senti is right) the submission was validated upon receipt.
I didn’t bash you, I didn’t even respond to you. My post was the first post in the thread.
However, the mainstay is to announce combo deals, which were in active negotiations, before the trials start, as they tried to do previously, but planned those trials (years ago) weren’t financially beneficial, so they didn’t go through with them.
They’ve been talking about active negotiations since 2022.
Where are they? If Senti is correct that the maa has already been validated (aka “cemented”), where is the outcome of those over year long active negotiations?
LP knows what the difference is between maa “cemented” versus your theory of need approval first.
The question is, did she speak accurately? I hope she did.
Dave stated they would announce acceptance/validation.
Senti states they don’t need to because receipt was validation.
For over a year, LP/NWBO stated they had active negotiations on financially beneficial trial combos that should be revealed when maa “cemented.”
If Senti is right about receipt equaling validation, then we should be seeing what these active negotiations were about
But
No ASM scheduled.
The lack of communication is probably partly causing the decline in price, but those with juice don’t care, because they can buy out gradually disillusioned retail that simply and reasonably want an update beyond the fact NWBO finally managed to submit thier maa.
It is published by “The Nature Publishing Group”. https://group.springernature.com/gp/group/media/press-releases/archive-2015/nature-publishing-group-announces-cell-death-discovery/17097648
But it is not, in any sense of the word, the Nature Journal.
It’s not a Nature article.
It is published by “The Nature Publishing Group”. https://group.springernature.com/gp/group/media/press-releases/archive-2015/nature-publishing-group-announces-cell-death-discovery/17097648
But it is not, in any sense of the word, the Nature Journal.
Continued: And when I said “yeah”, I was responding to your (AEKusterer) newer post on top, not the older post on the bottom. Most of your posts are very convoluted due you constantly reprinting old stuff.
Also, DCVax-l has complete data through 8.3 years (up to as many as 15 years for some patients) on every patient’s data from time zero. They don’t need ten years for approval. This is by far one of the most mature preapproval trials on the planet.
Yeah, but who here cares about surmvax?
Intratumoral DC Colorectal vaccine with CI (Keytruda) and 90 day phase II primary endpoint and one year secondary endpoint.
That’s what I figured. Thanks again.
Of course, I hope Dr. Bala is well. I assume his keyboard needs re-lettering, because he wore off certain characters.
e-r-t-u-s-d-f
Thanks. Good summary.
I read your post. I didn’t read the decision. Earlier yesterday I assumed KG was asking for more time because seventy something of the pages went against him. I assumed Posner didn’t agree to more time because she likely already has the amended complaint ready to go, and response on the ten or so pages completed.
I’m sticking with that. Responses to the judges decision due January 12. Neither one probably wants to submit too early, because it would give their opponent too much info. (Plus defendant has their hands full)
Don’t know when amended is supposed to be filed, but I’d assume it’s ready to go.
Thank you again.
US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA. https://pubmed.ncbi.nlm.nih.gov/35687337/
Hopefully it’s benign.
I think you read the 2023 chart correctly. However, I think Brexit, Covid and the requisite reestablishment of a massive infrastructure in the UK will finally give way to much much faster approvals. I do think being first to approve CRSPR was a stress test of sorts for MHRA, and they passed with flying colors (although it took 13 months). IMHO, that probably took a lot of staff.
I’ll bet they meet the majority of their 150 calendar day accelerated approvals (excluding clock off time) in 2024. I thought it was very wise of MHRA and NWBO to focus on expediting “high quality” maa submissions. Who knows, NWBO might be able to avoid what is normally a standard clock off period.
(The IRP for other applications should also decrease MHRA’s manpower requirements.)
For manufacturing inspections/approvals, the FDA already utilizes Mutual Recognition Agreements (MRA)
Mutual Recognition Agreements (MRAs) between FDA and foreign regulatory authorities allow drug inspectors to rely upon information from drug inspections conducted within each other’s borders. Under the Food and Drug Administration Safety and Innovation Act, enacted in 2012, FDA has the authority to enter into agreements to recognize drug inspections conducted by foreign regulatory authorities if FDA determined those authorities are capable of conducting inspections that met U.S. requirements.
MRAs:
Yield greater efficiencies for U.S. and foreign regulatory systems by avoiding duplication of inspections; and,
Enable reallocation of resources towards inspection of drug manufacturing facilities with potentially higher public health risks across the globe.
FDA has MRAs in force with the European Union, Switzerland, and the United Kingdom. https://www.fda.gov/international-programs/international-arrangements/mutual-recognition-agreements-mra
IRP, to my understanding, can/may be utilized by other jurisdictions after an initial approval in one jurisdiction — if the other jurisdictions start to apply it reciprocally. Because our first maa was submitted in the U.K., the U.K. can’t use another jurisdiction’s approval in order to utilize IRP here, (unless, for some odd reason, another jurisdiction leap frogged the UK — highly unlikely)
His other words are confirmatory and explanatory (why matters changed over past 18 months — probably due to improvements at MHRA). It sounds like things are on track with 150 day accelerated program (with possible clock off at 80 days if necessary), (and I’ll add maybe less than 150 days — which NWBO has not inferred)
Above and beyond the 150 day program, there may be new ways introduced in general guidelines to accelerate that further for some companies. Those guidelines (if any) have not been released yet. (Watch MHRA new every day this quarter for possible updates on general acceleration guidelines)
To add insult to injury, the fudster is cursed by Carnac the Magnificent.
pgsd, your find that IRP can be reciprocal means LP outsmarted Ex, KG and all the other haters.
It reminds me of a John Mayer lyric:
I just can't wait 'til my ten year reunion
I'm going to bust down the double doors
And when I stand on these tables before you
You will know what all this time was for
The clock initiation might even revert to date of receipt two days earlier, (as an MHRA Q&A seems to indicate).
Wow! As Johnny Carson would say, “I did not know that.”
"IRP allows us to access the expertise of trusted regulatory partners, who have already authorised products. In return, our partners can consider applications based on MHRA authorisations, creating a ‘win-win’ for regulators, developers of innovative treatments, and patients.”
Senti states receipt is not material because submission already announced. Senti contacts PR far more than me. Senti states receipt is synonymous with acceptance. Since January 1, 2024, MHRA gives faster review to high quality maa submissions. NWBO literally used two publishers and took an extra two weeks to make certain their maa submission was high quality. Prior to January 1, 2024, the MHRA validation time for MAAs had already sped up to four median business days. It is not inconceivable (it’s always best to say that word with a lisp) that a high quality maa submission discussed earlier at any presubmission meeting could be validated in hours to a day.
Despite my strong opinion that stakeholders should be alerted that the review clock has (likely) started, in order to get ready; an alternative opinion, given the above, is that most stakeholders (likely) are inherently aware, and thus should be expecting, as you say, that only a one day delay in announcement of submission indeed likely means NWBO is on the 150 day track (with possible clock stop or possible further acceleration). The company being conservative expecting a clock stop, but new further MHRA guidelines expected like “Swift” that could truly put pedal to metal.
“They” meaning KG’s side.
My guess is that they already know Posner’s team will satisfy the court with their upcoming amended complaint, which means they have to object to the other 70 something pages of the ruling that [didn’t] go their way. Judge will probably say, your objections are preserved. He’ll then want to move the amended complaint forward, only allowing mtd to be debated on the amended part and nothing else. Hoffman is the expert on this stuff.
I see, so you are saying the validation was announced to you? Noted.
Validation Assessments take a few days to a few/several weeks. The median has been reduced to about a week.
Some companies, like vertex, received validation confirmation about 30 to 40 days after completing maa submission.
My guess is that they already know Posner’s team will satisfy the court with their
Upcoming amended complaint, which means they have to object to the other 70 something pages of the ruling that don’t go their way. Judge will probably say, your objections are preserved. He’ll then want to move the amended complaint forward, only allowing mtd to be debated on the amended part and nothing else. Hoffman is the expert on this stuff.
No bets either way. This makes it looks like they revert the validation to the original receipt date after the validation assessment is concluded.
https://www.gov.uk/government/publications/common-issues-identified-during-clinical-trial-applications/common-issues-validation
Thanks to Ockain for the link.
I appreciate that Posner is not agreeing to the extension. KG’s team is not helping itself out.
To me, what this means, is that Posner is already prepared to amend, as in, it’s already drafted imho. KG’s people probably know it. KG understands they received a Pyrrhic victory from the last ruling.
Imho.
Without AI’s assistance, I generated a list of some companies announcing MHRA validation for their MAA. I think they will stand up to scrutiny.
https://www.onclive.com/view/uk-accepts-marketing-authorization-application-for-sugemalimab-in-metastatic-nsclc
December 19, 2022
https://www.globenewswire.com/news-release/2022/06/14/2461980/0/en/EQRx-Announces-Acceptance-of-Marketing-Authorization-Application-by-the-UK-s-Medicines-and-Healthcare-Products-Regulatory-Agency-for-Aumolertinib-in-EGFR-Mutated-Non-small-Cell-Lun.html
June 14, 2022
https://www.technologynetworks.com/genomics/product-news/vertex-and-crispr-therapeutics-announce-mhra-marketing-authorisation-application-validation-for-369926
February 26, 2023
https://pharmatimes.com/news/ema,_mhra_to_review_vertex_kaftrio_for_children_with_cf_1370364/
May 20,2021
https://www.biospace.com/article/releases/uk-s-mhra-accepts-humanigen-s-submission-of-lenzilumab-for-marketing-authorization-in-covid-19-for-expedited-rolling-review/
July 9, 2021
https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-uks-medicines-and-healthcare-products
Sept 8, 2021
https://www.biospace.com/article/releases/athenex-announces-uk-mhra-validation-of-the-marketing-authorization-application-for-oral-paclitaxel-and-encequidar-for-review/
November 29, 2021
https://www.mundipharma.com/Napp-announces-acceptance-of-their-Rezafungin-Marketing-Authorisation-Application-for-the-Treatment-of-Invasive-Candidiasis-to-the-UK-Medicines-and-Healthcare-Products-Regulatory-Agency
November 16, 2022
And yet you ignored my two recent challenges to your January 3rd post.
Actually you two disagree on a very fundamental point.
Actually Hoffman and Senti are at odds right now.
Senti is convinced all submissions are always immediately validated.
Whereas Hoffman believes, like I do, that validation review is made over the course of days, and sometimes weeks. A validation report is generated, which includes among other things, a clear statement regarding whether the submission was validated.
If validated, it appears the validation reverts to the date of submission.
Senti wants the discussion closed. Hoffman advises against announcing validation, but get this, he’ll be “pleasantly surprised” if they do.
True. As I said, I had AI (Bard) generate that list for me.
I have since tried to locate these announcements anywhere, and they were not to be found.
I confronted Bard with this last night (it did not save my conversation from yesterday), but it admitted it made it all up because it just wanted to show it could give me an answer.
I should have pursued this earlier, but I found announcements of validations on my own (like Vertex/Crspr), and I thought AI could give me a quick list of more announcements.
My bad.
I asked Bard if it should really be dealing with the public if it was willing to lie? It stated it would do better. After further questioning, it said it would probably end up pulling the same thing on someone else.
Again, my bad for using AI. I’ll try to create a list of similar length over the next couple days without AI.
No one pays me, unlike you. I’ve presented two posts (not including this one) challenging her position. You and Senti are still at odds with NWBO’s Dave Innes who suggested of course they would announce validation/acceptance, as it is a milestone certainly bigger than PIP.
You are at odds with the MHRA who state that validation reports are completed a number of days after submission, and validation case reports, among other things, confirm or deny validation.
I await Senti’s responses to my messages.
Why are so many of you opposed to Dave’s emails and the fact that validation does not formally get decided upon until days after submission?
Actually, no, a validation report, which the MHRA has been completing between about a week to 30 days from case initiation, confirms or denies validation and provides all the reasoning.
If it is valid, it appears the clock continues to be counted from the original date of submission, if it is not valid, it starts from the date of resubmission.
Announcing validation can help many different parties prepare for a new product about to enter the commercial market. It gives everyone an approximate working timeline.
Dave Innes, suggested, if they announced PIP, why would they not announce submission and validation.
Many here, including Senti, are at odds with that position. I questioned some of Senti’s reasoning in two posts, but she has not responded to either post.
You are not making sense. Those are not mandates. They are goals.
Will you stop posting if it’s not approved by the end of March this year.
Senti, how do you square your theory of immediate validation upon submission, with the MHRA stating their goal is to validate within two weeks?
Euro Roundup: MHRA misses performance targets amid resource constraints, Brexit backlogs
Roundups
Roundups
| 21 July 2022 |
Nick Paul Taylor
Euro Roundup: MHRA misses performance targets amid resource constraints, Brexit backlogs
The UK Medicines and Healthcare products Regulatory Agency (MHRA) missed multiple performance targets for its 2021-2022 financial year due to resource constraints, Brexit backlogs, and additional reasons.
MHRA started the financial year aiming to produce 97% of validation reports for new marketing authorization applications within 14 days of case creation; instead, the agency achieved the 14-day target 83.4% of the time.
“Embedding centrally authorized products (CAP) grandfathering transition activities resulted in backlogs in Q1 and a missed target,” MHRA wrote in its report. CAP grandfathering refers to the conversion of all existing EU marketing authorizations to British authorizations because of Brexit. MHRA cited the same pressures as a reason why it missed the target in its 2020-2021 financial year.
With the backlog cleared, MHRA said “performance was recovered” in the second quarter and “returned to target” in the second half of the year
MHRA is looking to its new organizational structure to improve performance against other targets, such as the 80-day goal of assessing applications to market new active substances 97% of the time.
A Marketing Authorisation Application (MAA) Validation Report for a single drug application is a document issued by a regulatory agency after assessing the completeness and administrative acceptability of an MAA submission. It essentially confirms that the application includes all the necessary information and documentation required for further scientific evaluation.
Here's what an MAA Validation Report for a single drug application typically includes:
1. Case Information:
Date of application submission
Application number
Applicant name and contact details
Drug product name and proposed trade name(s)
Active pharmaceutical ingredient(s)
Dosage form and strength
Therapeutic indication(s)
2. Administrative Assessment:
Confirmation of payment of required fees
Review of the electronic submission format and compliance with eCTD specifications
Assessment of the presence of mandatory modules and sections within the eCTD structure
Identification of any missing or incomplete documentation
Verification of the validity of relevant certificates and licenses
3. Outcome:
A clear statement indicating whether the application is administratively validated or not.
If not validated, a list of deficiencies that need to be addressed before further evaluation can proceed.
If validated, a timeline for the start of the scientific assessment.
4. Additional Information:
Information on how to address any discrepancies or missing information.
Contact details for the agency responsible for further assessment.
Links to relevant guidance documents and regulations.
It's important to note that the specific content and format of an MAA Validation Report may vary depending on the regulatory agency involved and the applicable regulations. Therefore, it's always recommended to consult the agency's guidance documents and specific requirements before submitting an MAA.
Will you stop posting if it isn’t?
Why did these occur on two different dates Senti?
1. In December 2022, CRISPR Therapeutics and Vertex Pharmaceuticals completed regulatory submissions for exa-cel with the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) in ….the U.K., respectively. https://crisprtx.gcs-web.com/news-releases/news-release-details/crispr-therapeutics-provides-business-update-and-reports-first-5
2. (February 6, 2023) Vertex Pharmaceuticals (Europe) and CRISPR Therapeutics (NASDAQ: CRSP) have announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has validated the Marketing Authorisation Application (MAA) of exa-cel for the treatment of sickle cell disease (SCD) and transfusion dependent beta thalassaemia (TDT) in Great Britain.
Vertex-and-CRISPR-Therapeutics-Announce-MHRA-Marketing Authorisation Application Validation for CRISPR/Cas9 Gene-Edited
Published: February 6, 2023
https://www.technologynetworks.com/genomics/product-news/vertex-and-crispr-therapeutics-announce-mhra-marketing-authorisation-application-validation-for-369926[/url][tag]insert-text-here