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New IB webinar with latest animal research on GaM. Latest results show that radiation effect in GaM treated animals led to a quadrupled survival benefit. Wow!

I see that the entry on the MCW site for the Gallium Maltolate phase 1 has disappeared. I assume it's been removed due to not requiring further recruits. Hopefully, we will get a progress update that confirms this.

For a decent jump they need to release good efficacy results. We already know GaM is safe - doses exceeding the final 2500mg were used by Titan Pharma in the original clinical trial without issue. The bar for treatment effect is very low given the existing treatments do so little to extend survival. I believe the Tumor Treatment Fields device, which uses electrical fields to disrupt glioblastoma cell replication, offers only a few additional months of survival. Likewise, the existing drugs either provide a small additional survival or merely improve quality of life without extension. It is truly a terrible disease. It appears anecdotally that GaM has excellent tollerability, so any modest improvement in overall survival would improve the outlook for a glioblastoma patient.

I just checked clinical trials.gov and the MCW website and both indicate the phase 1 is still open for recruitment. How does this tally with being told the end of phase 1 meeting with FDA will occur by the end of this year?

From the newsletter...

Dr. Jennifer Connelly, the lead investigator on the Gallium Maltolate Phase 1 trial, will be presenting at the Medical College of Wisconsin’s Department of Neurology’s 50th Anniversary, Celebrating the Advances in Neurological Care. Saturday, September 21st, 2024 | 8am – 4pm

I found this which has some more detail - basically snippets of each section.

https://www.sciencedirect.com/science/article/abs/pii/S014181302405582X

If it is true that the phase 1 is nearing completion, the the status of the clinicaltrials.gov record should be updated to reflect that recruitment has now closed.

It's not clear to me what the dosing rate will be. The clinical trials record states that 500mg capsules will supplied but not how many will be given in each dose?

When can we expect the next update from the investigators in the ph1?

What dose is being used in the EAP given that dose.findung is still in progress, or has this now been determined?

I assume trial participants are to be kept on drug as long as their disease is controlled rather than for a maximum of 6 months (as per secondary outcome measures).

The drug, branded as voranigo, is used to treat a form of brain cancer, called Grade 2 IDH-mutant glioma, in patients who have had surgery.Voranigo was approved on the basis of a late-stage trial, where patients who took the treatment showed progression-free survival of 27.7 months compared to 11.1 months with the placebo group.

With the approval, Agios Pharmaceuticals (AGIO.O), opens new tab will receive up to $1.1 billion in milestone payments from Servier and Royalty Pharma (RPRX.O), opens new tab.

Sure. "Signal" is terminology used to indicate that there MIGHT be an indication of an effect based on the results seen. It tends to be used in early stage trials where the population size is not large enough to demonstrate statistical significance. Late state trials must demonstrate a high degree of certainty that the effect is not due to chance (statistically significant).

Looking at the PR further, the 3.8m was for a subset (newly diagnosed unmethylated) so the bar is even lower.

Thanks for this. I just read the PR and I missed the fact the result was in NEWLY DIAGNOSED disease. It says that no efficacy signal was detected in recurrent disease, similar results to other drugs tested in GBM-Agile. If, and it's a big if, GaM shows a signal in the phase one recurrent disease population, it would seem probable that it has higher efficacy than the other agents tested to date...

Kazia Therapeutics Limited (NASDAQ: KZIA) announced that paxalisib improved overall survival by 3.8 m. Shares closed up 248%.

Kazia reported a 3.8 improvement in overall survival from their GBM agile trial results. They plan to discuss accelerated approval on the basis of the results. An additional 3.8 months may not sound much but it shows just how few options there are presently and why GaM should garner interest.

Accelerated approval is not out of the question. The approval path is well suited to treatments which show some efficacy in terminal disease.

Hopefully, the late stage ph1 data will be positive. Having waited 2 plus years, It seems a bit crazy to ditch before we really even have the results of using the 2500mg dose. The animal testing, which demonstated effect in tumor growth, was at much higher doses than the starting doses in the ph1.

Xviolet

We are probably due an uodate from Dr. Connelly on the ph1 progress. I've watched a number of her Q&A sessions and have been impressed by her carefully considered answers. I regard Dr. Connelly as the ultimate source off truth regarding the clinical program.

Cancer trials normally report results based on the effect on tumor progression. A drug that at least halts further growth may be deemed effective. I would expect something similar from the combined late stage p1 cohort plus any EAP patients. Although progression free survival (PFS) and overall survival (OS) are popular endpoints, tumor shrinkage could also be reported upon. Given that its been stated that initial treatment is 2 months, and that Gliiblastoma is auch an aggresive cancer, there is an expectatiin that outcomes based on imaging pre/post treatment could be announced months after recruitment closes.

I think we need a strong efficacy signal in the near term to improve funding prospects. As we know, they are only now treating at or near max tolerated dose (expected to be 2500mg). There were due to be 16(?) in this group. If they treat say another 20 under EAP then that might be enough to demonstrate a positive effect.