NorthWest Biotherapeutics Inc (NWBO)

[OncoJock]

I'm starting to smell stiff competition from Harvard.

The Crimson crew, helmed by David Reardon at the Dana-Farber in Boston, may be on the verge of overtaking our crew that includes Steven Brem at Harvard's Ivy League arch-rival, the University of Pennsylvania in Philadelphia. Penn's crew -- which also boasts top investigators in Los Angeles, London, and other cities -- appears to have its sights set on winning an approval by the MHRA (the British equivalent of the FDA). Harvard's crew -- which also includes top investigators in Buffalo, Seattle, and other cities -- appears to be seeking an accelerated approval from FDA. The trophy could be bragging rights for the team that develops the first systemic therapy advancing the standard of care in glioblastoma multiforme (GBM) since temozolomide in 2005.

The finish line may be closer than we think.

Here's why:

In the discussion section of the report of the phase 2a study of the SurVaxM vaccine trial in ndGBM, published in the Journal of Clinical Oncology in 2022, these words are found:

OS (overall survival) can be affected by subsequent treatments following
initial tumor progression and off-study events. However, in
the current study and accounting for censoring, PFS (progression-free survival) correlated
strongly with OS (r 5 0.79), suggesting that therapies
subsequent to the off-study date had modest impact
on OS.29 Thus, PFS may represent an acceptable surrogate
for OS as a primary end point in patients with nGBM treated
with adjuvant TMZ and SurVaxM following surgical resection
and chemoradiation.

As we all know, a trial built around the PFS endpoint can be concluded more quickly than one built on OS.

But.... can a drug win FDA approval based "only" on a phase 2 trial? Isn't a phase 3 trial normally required?

Maybe not. When I put this question to ChatGPT, here's what I was told:

Q: Can a drug win FDA approval for a rare disease based on results of a randomized phase 2b placebo-controlled trial?

A: Yes, in certain cases, a drug for a rare disease can potentially win FDA approval based on the results of a randomized Phase 2b placebo-controlled trial. The FDA recognizes the challenges associated with conducting large-scale clinical trials for rare diseases due to the limited number of eligible patients. As a result, they have implemented specific regulatory pathways to facilitate the development and approval of drugs for rare diseases.

The FDA's Accelerated Approval pathway and the Breakthrough Therapy designation are two mechanisms that can expedite the approval process for drugs targeting rare diseases. These pathways allow for a more flexible approach, taking into account the unique circumstances of rare diseases.

Under the Accelerated Approval pathway, a drug can receive conditional approval based on a surrogate endpoint that is reasonably likely to predict clinical benefit. A surrogate endpoint is a measurement or biomarker that is used as a substitute for a clinical endpoint, which is a direct measure of how a patient feels, functions, or survives. The drug must still undergo further studies to confirm its clinical benefit, but the initial approval is granted based on the Phase 2 trial results.

Now connect that dot to the next one:

At the end of the JCO report on the Phase 2a study, the Harvard team reports that a randomized, placebo-controlled trial of SurVaxM is underway. That trial, called the SURVIVE trial, is shown on ClinicalTrials.gov (NCT05163080). The estimated enrollment is 265 patients -- which is large for a phase 2 trial -- the estimated primary completion date is this summer, and the estimated final completion date is next spring.

Furthermore, we know that David Reardon is interested in the DCVax trial because he travelled from Boston to New York City to be present at NYAS in May of last year to ask questions of Dr. Mulholland.

This is why I smell competition from Harvard.

-- OJ