Imvax Reports Phase 2b Trial Data for IGV-001 in ndGBM

The therapeutic agent missed its PFS Primary Endpoint. Surprised, we are not.

On 2-Dec-2025, Imvax reported top line data from its Phase 2b clinical trial of IGV-001 (see here and here).

Bottom Line: IGV-001 missed its pre-specified Primary Endpoint (PEP) of statistically significant extension of Progression Free Survival (PFS).

However, a reader of the press release issued by Imvax would be challenged to understand that the trial missed its PEP. Instead, the company decided to put a positive spin on the results by noting that the trial data showed an extension in median Overall Survival (mOS), which was the Secondary Endpoint (SEP). No supporting #Data was provided to support the claim. Perhaps, the company will present such data at a future medical conference or in a reputable journal.

The company’s PR also indicated that Imvax would meet with the FDA in an attempt to somehow gain approval for IGV-001 despite the clinical trial miss. In the days prior to Jan-2025, there have been a few recent precedents for jawboning (bludgeoning?) the FDA into granting approval for candidates that miss pre-specified PEPs in indications that are severe and lack any good therapeutic options. In particular, we note the controversial approvals of Sarepta’s Elevidys® for Duchenne’s Muscular Dystrophy (see here) and the initial approval of Biogen’s Aduhelm® (aducanumab; see here and here) for Alzheimer’s disease. In both cases, the aggressive and vocal actions of patient advocacy groups played a significant role in backing the FDA into an uncomfortable corner, and even over-ruling the recommendations of the Advisory Committees that reviewed the NDAs.

Always Let the Facts Get in the Way of a Good Story

We refer to this unfortunate Spin Doctor practice in Biopharma as “never letting the facts get in the way of a good story”. In contrast, we tell all the CEOs of our portfolio companies to do the exact opposite: ALWAYS let the facts get in the way of a good story. Those who listen get the support of our syndicates; those who do not generally become unemployed rather quickly.

Why, Dear Reader, would Imvax choose to pursue such a strategy…especially in a field that has been historically unencumbered by success and plagued by poor science and questionable clinical trial practices? Well, as my father told me decades ago, “When you don’t know the answer, follow the money”. Imvax has raised substantial amounts of investment capital in the last 6 years (see here), and the investors would understandably like to enjoy an ROI. The pressure to deliver an ROI has been known to tempt CEOs to suspend disbelief; issue a Spin-a-Palooza press release; and beat a hasty path to the FDA with vocal patient advocacy groups in tow. While we cannot predict the response of the FDA to the Imvax strategy (particularly in light of the #Chaos happening at the FDA following 20-Jan-2025; see here and here), we would advise that you get your popcorn ready as this will be a jolly good show.

The Bigger Picture

The questionable Imvax regulatory strategy in the face of its PEP miss in the Phase 2b trial may have a much larger spillover effect on the entire field of clinical development for GBM/HGG. Why?

Imvax was one of the first companies with a therapeutics candidate for GBM/HGG in late stage clinical development to get the FDA to consider PFS as an approvable PEP versus the Agency’s historically dogmatic insistence on mOS as the only approval PEP (in the wake of the bevacizumab (Avastin®) approval debacle for GBM). In the last 18 months we have become aware of at least four other companies also pursuing the PFS regulatory strategy for GBM after meeting with FDA. PFS as an approvable PEP is common in other forms of cancer apart from GBM/HGG, but has not been permissible for the past 15 years in GBM/HGG on account of the Agency’s embarrassment regarding the misguided bevacizumab approval. Thus, the Imvax #Data and regulatory strategy runs the risk of pushing the FDA back into its “mOS only for GBM approval” bunker.

Trials with mOS PEPs are longer, more expensive and more difficult to conduct relative to trials with a PFS endpoint, especially as new therapies advance which extend mOS. Moreover, one needs to consider the clinical situation and patient Quality of Life when using mOS as the PEP. Very few patients want to be bedridden, wearing an adult diaper and suffering frequent seizures or dense aphasia just because mOS statistics have to be obtained.

The Road Ahead for IGV-001

The FDA may eventually approve IGV-001 for GBM despite the Phase 2b clinical trial miss. Predicting what will happen at the FDA these days is a parlor game that those of us in the Biopharma industry conduct on almost a daily basis because the New Look FDA seems to be driven by forces other than rigorous evaluation of #Data and scientific evidence. Ugh!

Assuming that IGV-001 gains approval, the battle is only partially won. Imvax will still have to get acceptance from both the Neuro-Oncology community to write for the therapy and the Payers to underwrite the cost. Judging from the dozens of phone calls that we have received from NOs and Payers over the last 48 hours, this will be an uphill battle.

Maybe the facts will ultimately get in the way of a good story after all.

The Real World Difference Between PFS and mOS

On this score and offering my own personal note, Julie had an mOS of 38 months which is extraordinary for a GBM patient with her clinical presentation, and is a testament to the power and innovative thinking of Team Julie. She lost her durable Complete Response in Mar-2024 when we had to suspend the use of pembrolizumab (Keytruda®; Thank You, Merck for being an enormously supportive partner for MissionGBM patients over the last 3+ years) due to a Grade 4 irSAE that perforated her colon (see here). We knew she would convert to rGBM status as soon as the CD8+ T-cells in the TME became exhausted. Right on cue at 2.5 half-lives after the last pembrolizumab infusion, we got the first Bad Scan in more than two years. The tumor grew rapidly and she was presented with the option of an awake craniotomy in Aug-2024 in order to debulk the tumor and provide runway for Team Julie to initiate an even more advanced immunotherapy with additional prophylaxis against irAEs.

While the awake crani was successful and expertly perfomed by one of the best neurosurgeons on the planet (Dr. Nduka Amankulor; Hospital of the University of Pennsylvania), Julie exhibited dense expressive aphasia and advancing neuromotor deficit in the post-surgical period. Because we had conducted detailed Goals of Care planning sessions early in Julie’s ndGBM period (see here), she made it clear that she did not want to live as a non-ambulatory aphasic who was completely dependent on her caregivers (principally me) to keep her alive. So we made the tough decision to suspend therapy and transition her to home hospice care despite the belief that the new therapeutic protocol could keep her alive for a significant additional period of time. Julie died peacefully in bed with me lying next to her in Jan-2025.

That, Dear Reader, is the Real World difference between PFS and mOS.

Onward!

Note about the future of Mission GBM. We had not intended to publish any new content until the one year anniversary of Julie’s death (Jan-2026); however, the Imvax PR and the strident response that it generated prompted us to publish this post. Life is what happens while we are busy making other plans. While we have not been writing and speaking much over the past year, we have been very active. Stay tuned for our emergence from stealth mode in 1H2026 with news regarding what we have been doing, and the multiple investments and Board memberships that we have undertaken to advance new therapies for GBM and HGGs. The battle continues.