Unsurprisingly, much of the conversation at #ASCO15 has been centred around that currently in vogue buzzword of "immunooncology", which has gone from a budding new area of excitement in cancer therapy into a fully bloomed mosaic bursting with potential and new hope. New hope and less hype, which makes a refreshing change! The major focus of this axis of research is on the PD-L1/PD-1 checkpoint targets, with both Merck and BMS leading the charge.
The (feeding) frenzy in the PD-1 field is primarily due to what appears to be a key combination of impressive efficacy and strong pricing capacity, and some analysts predict that the market for this class of drugs could reach a whopping $30B by 2020. The stakes are high and the competition is fierce, with Roche and AstraZeneca on the heels of Merck and BMS, with Novartis, Pfizer and Sanofi hoping to catch some big crumbs falling off the forerunners' tables
That the stakes are incredibly high was underlined by a massive $7B loss in market cap in an afternoon for BMS based on very recent data that their Opdivo may not be effective in PD-L1 deficient patients with NSCLC lung cancer, which will cause payers to force BMS to test individuals for their PD-L1 status, and cut the market penetration for Opdivo in lung cancer quite significantly. The search for better biomarkers and predictors of response to immunotherapy was a hot ticket at ASCO, and it seems that DNA mismatch repair was clearly superior to PD-L1 in terms of predicting positive responses to Merck's Keytruda, which some are now referring to as "King Keytruda".
That the stakes are incredibly high was underlined by a massive $7B loss in market cap in an afternoon for BMS based on very recent data that their Opdivo may not be effective in PD-L1 deficient patients with NSCLC lung cancer, which will cause payers to force BMS to test individuals for their PD-L1 status, and cut the market penetration for Opdivo in lung cancer quite significantly. The search for better biomarkers and predictors of response to immunotherapy was a hot ticket at ASCO, and it seems that DNA mismatch repair was clearly superior to PD-L1 in terms of predicting positive responses to Merck's Keytruda, which some are now referring to as "King Keytruda".
It can often be difficult to get attention on other targets or modalities when one has a superstar like PD-1 hogging the spotlight, but there was some other news that most definitely caught my attention and shone similarly in terms of being a game-changer. Merck's Keytruda is cutting it's teeth on melanoma (among a slew of other cancer indications), but scientists at Amgen have come at the same problem with a very enticing alternative version of immunotherapy that is currently making the news and generating some excitement of its very own.
Amgen has come up with a modified form of Herpes Simplex I virus (yes, the same one that causes those nasty cold sores!) that is known to readily proliferate inside cells and cause them to burst, hence the cold sores! But this modified version of the virus (known at T-Vec) has two genes removed which prevents it replicating in healthy cells but does not prevent it doing it's thing in cancer cells. This leads to rupture of only the cancerous cells, leaving healthy tissue intact. Additionally, T-Vec has been engineered to produce the GM-CSF cytokine, a flashing beacon for the immune system, which thus triggers an immune response right where it's needed - the tumour site.
Even though I had heard little about it (but then again, I am not a cancer researcher!), I was surprised to hear that Amgen's clinical success with this agent reflects data from a 436 patient Phase III clinical trial, which means that we could be less than a year away from this agent being marketed. The data obtained were in patients with inoperable melanoma, and T-Vec produced positive responses in roughly 16% of patients at the six month mark, compared to just 2% in those receiving the control therapy. Strikingly, those with Stage III or IV cancer survived for on average of roughly 40 months, compared to just circa 20 months for earlier stage patient receiving the control therapy.
It is a quite brilliant (perhaps brilliantly obvious, to some) concept - to use the weaponry of a major infectious enemy of mankind, viruses, to attack another major internal enemy of mankind, cancer, and turn one enemy against another to our benefit. Not so much a divide and conquer, but more of a unite and vanquish. Once we prevent the virus from destroying normal human cells but facilitating its targeting of more rapidly dividing tumour cells, thereby leading to their rupture and exposure to the immune system's own arsenal of defence, well, that begins to look like progress!
It is a quite brilliant (perhaps brilliantly obvious, to some) concept - to use the weaponry of a major infectious enemy of mankind, viruses, to attack another major internal enemy of mankind, cancer, and turn one enemy against another to our benefit. Not so much a divide and conquer, but more of a unite and vanquish. Once we prevent the virus from destroying normal human cells but facilitating its targeting of more rapidly dividing tumour cells, thereby leading to their rupture and exposure to the immune system's own arsenal of defence, well, that begins to look like progress!
The fact that some patients still responded to treatment three years later is indicative of the promise in this approach, which is going to be a first-in-class therapy for skin cancer and will significantly broaden the landscape of cancer treatment. This is the first time that a virus has been successfully used in this fashion to attack cancer cells, and obviously clinicians will eagerly anticipate the potential use of T-Vec in other types or cancer, as well as it's clear potential to be used in combination with the latest checkpoint inhibitors - it could be an immunotherapy bloodbath against cancer!
No comments:
Post a Comment