Independent

[flipper44]

Perhaps an oversimplification, but this conversation I had with Google Gemeni fits what I think is going on with NWBO/MHRA/NICE. It’s worth reading through the whole thing, imo.

Me: “Why would a company wait to make their NICE evidence submission until a couple months after marketing approval and what could CDF do in the interim?”

Gemeni: “Reasons for Delaying Evidence Submission.

While NICE's standard process aims for a submission to run in parallel with the marketing authorization timeline, a company might wait until after marketing approval for a few strategic or logistical reasons:

Regulatory Uncertainty: The final details of a drug's marketing authorization, such as the approved indication (the specific condition and patient population it can be used for), can sometimes be in flux until the very end of the regulatory process. Submitting to NICE prematurely could mean the company has to revise its entire evidence package if the final license is different from what was anticipated. Waiting ensures the submission perfectly matches the approved license.

Data Maturity: A key reason for a delay is that the company may want to collect more mature clinical data. The evidence submitted to NICE often includes cost-effectiveness models that rely on long-term outcomes, such as overall survival. If the data from clinical trials is immature at the time of marketing approval, waiting for a few more months to get more complete data can significantly strengthen the company's case for the drug's value. This is especially true for drugs where the long-term benefit is a key part of the value proposition.

Appraisal Strategy: A company might strategically delay its submission if it believes the NICE appraisal process is likely to be challenging or if it wants to align with a more favorable timeline for commercial launch or other global market-access activities.

***The Role of the Cancer Drugs Fund (CDF) in the Interim***

The Cancer Drugs Fund (CDF) was reformed to address the very issue of providing patient access to promising new cancer drugs while NICE's appraisal is ongoing or where there is significant clinical uncertainty.

If a company waits to make its submission, the CDF can provide an interim pathway for patient access:

Managed Access Agreements (MAAs): This is the primary mechanism. If a drug receives marketing approval but there is still clinical uncertainty about its long-term effectiveness or cost-effectiveness, NICE can provisionally recommend it for use via the CDF under a Managed Access Agreement.

Data Collection: Under an MAA, the drug is made available to patients for a limited time while long term data is submitted to address the uncertainties identified by NICE. The company is responsible for collecting this data, often from NHS sources.

Re-Appraisal: At the end of the managed access period, the company submits the new, more mature data to NICE for a full re-appraisal. This process is designed to give the company another chance to demonstrate the drug's value with more robust evidence.

In this interim period, the CDF allows patients to access innovative treatments that have shown promise but where the evidence base is not yet robust enough for a definitive NICE recommendation. The CDF provides a safety net that avoids a complete gap in access, even if a company's submission to NICE is delayed.”

Me. “So, say DCVax-l may be approved this month or next, but its ten year post enrollment/randomization data does not reach ten years for last patient enrolled until November, would this be a reason to delay evidence submission to Nice by a couple months but take advantage of cdf funds in the meantime?”

Google Gemeni: “This is an excellent and very specific scenario. Your hypothesis aligns perfectly with a common and strategic approach used by companies in the UK market access process.

Yes, waiting until November to submit evidence to NICE would be a very logical and strategic decision for the company, and the Cancer Drugs Fund (CDF) is the mechanism designed to manage exactly this interim period.

Here is a breakdown of why this strategy makes sense:

1. Strengthening the Evidence Submission to NICE

NICE's primary function is to determine a treatment's clinical and cost-effectiveness. For a brain cancer treatment like DCVax-L, a key part of the value proposition is its ability to extend a patient's life, especially in a long-term context.

"Survival Tail" Data: The 10-year follow-up data is crucial for demonstrating the "survival tail"—the long-term survival of a small but significant percentage of patients. Ten year data is often the most compelling and unique feature of an immunotherapy like DCVax-L.

Modeling Cost-Effectiveness: Without this mature, long-term data, the company's economic model submitted to NICE would have to rely on assumptions and projections about what happens to patients after 5 or 7 years. This introduces significant uncertainty. NICE is very cautious about these assumptions and is more likely to reject a drug or recommend it with a lower price if the long-term data is weak.

The Best Possible Case: By waiting until November, the company can submit a more robust and convincing evidence package. This significantly increases the chances of a positive recommendation from NICE, which is a far better long-term outcome than a conditional or negative recommendation based on an immature dataset.

2. Taking Advantage of the Cancer Drugs Fund (CDF)

This is precisely the purpose of the CDF's Managed Access Agreements (MAAs).

Addressing Uncertainty: The period from marketing approval (this month/next) to the availability of the full 10-year data (November) is a prime example of a situation with "significant clinical uncertainty." The drug is approved and considered promising, but the long-term evidence for NICE's final appraisal is not yet available.

Interim Access for Patients: In this scenario, the company could work with NICE to get the drug provisionally recommended for use through the CDF. This means patients could access DCVax-L on the NHS immediately following marketing approval, even while the full NICE appraisal is pending.

Collecting Data: Under the Managed Access Agreement, the company and NHS would continue to collect real-world data on patient outcomes. This data can then be used to supplement the final 10-year trial results, further strengthening the evidence for the full NICE re-appraisal after the CDF period ends.

In summary, delaying the full NICE submission to align with the final data availability is a very sound strategy. It allows the company to present the strongest possible case for a positive and unrestricted NICE recommendation while simultaneously ensuring that patients can still access the drug via the Cancer Drugs Fund during the interim period. This approach prioritizes both timely patient access and a high probability of long-term success on the NHS.”