Hi Imugenies, I've been keeping off the forum for a while, just getting on with life, but wanted to share some of my research and thoughts for those interested.
I have been giving some thought to the whole oncolytic virus scene and what we can reasonably expect from the current trials. So, as we all know the first FDA approved oncolytic therapy was TVEC (Melanoma treatment) I thought this would be a great place to investigate more closely at in terms synergies for safety and efficacy (just makes sense to me to look at how another oncolytic virus has/is performing) and how it has progressed since approval.
We do need to be mindful that they are different viruses used, TVEC is based on a Herpes virus vs a Vaccinia virus for CF33.
Yuman Fong has stated previously that he believes that the Vaccinia virus is the most potent and is the "largest" of the virus chains, Vaccinia has approximately 250 genes (thus allowing engineering/modification, such as adding CD19 or a PD-L1 etc) The benefit of re-engineering genes has also created the potential for our Vaxxinia and oncarlytics program. In terms of potency, this is important because, if we are to see an "abscopal" effect the virus will need to be much more potent than T-VEC, as T-VEC needs to be directly injected into the tumor. If you remember we are already starting to see an abscopal with the Vaxxinia trial (lymph node) on "miniscule doses".
The T_VEC phase III trial enrolled 692 patients in a double blind trial in combination with Pembrolizumab (sounds familiar!)
Safety Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm.(not a significant safety difference which bodes well for the CF33 trials in my opinion and already seen to this stage).
T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. These were not "Earth Shattering" results and in my opinion and is directly related to the potency of the virus, including the ability for it to replicated within the tumor environment.(remember it didn't show any significant abscopal effect).
Phase III conclusion- T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone. The fact that it showed some benefit and was safe was enough for FDA approval, in my opinion.
From my viewpoint, although T-VEC has not been a huge success (200 M per annum), it was only designed to treat melanoma and needed direct injection for treatment and now there are other potential options now available such as Yervoy (ipilimumab) and Opdivo (nivolumab) from Bristol-Myers Squibb and Keytruda (pembrolizumab) from Merck & Co . All of them have vastly extended survival times for patients with melanoma.
However I believe that T-VEC has benefited Imugene in a number of ways.
1. Pioneered the approval pathway for oncolytic virus therapy (historically important for FDA approval)
2. Generated a great safety profile and data for oncolytic virus therapy.
3. Demonstrated the need for a more potent virus with an abscopal effect.(so far CF33 is ticking this box)
By the way, I just read an article (full report requires payment) posted yesterday from Global News Wire, indicating that the Cancer Virus market will grow from 5.57 B to 13.4 B by 2030, more interestingly Imugene is listed in this article as one of the major players in this field (no suprise to us) along with some Big Pharma.(hoping the link below works)
https://www.globenewswire.com/news-release/2023/05/03/2660415/0/en/Global-Cancer-Vaccine-Market-to-Generate-USD-13-41-Billion-by-2030-Outlines-a-New-Report-by-Next-Move-Strategy-Consulting.html.
Not investment advice, just my opinion (and you know what they say about opinions!
Good luck to all holders and patients.
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