Going viral - kissing skin cancer goodbye with a cold sore?!

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". 

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!

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!

When your social media numbers are stronger than your scientific data - there's a problem!

   

I've commented about the use of social media for business, previously, and while collectively they are undoubtedly a tool that accesses huge numbers of customers and potential clients in an instant, so do they also allow rapid dissemination of misleading or even totally false information - just ask any celebrity! 

Although we tend to not think of social media in association with serious, life-changing matters such as disease and drug development, if you spend any time at all on Twitter (in particular) or Facebook these days, you will see that big pharma are very much alive and well in the social media world of instant information transfer. Pharmaceuticals are big business, there is a lot at stake, and now one of the quickest and easiest ways to hear of new clinical trial outcomes and drugs about to be commercialized is via social media. 

While this is a good thing, and is no doubt also good for business, I came across a case recently where an outfit appear to be using social media as a tool to lobby (some might say, bully) the FDA,  rather incredibly in the absence of any credible data, and using the desperation and unmet need of patients and their families to pile on the pressure in support of their cause. Although it is a strategy that might have worked in certain other types of business (i.e. entertainment), it is highly irregular to see social media used to apparently attempt to intervene with regulatory authorities in the business of marketing approval for new drugs. 

Such is the case with a certain Winston Ko, CEO of Genervon, who nucleated a far-reaching social media campaign to push the FDA into an accelerated approval process for their "application" on a supposedly mega-exciting new drug for amyotropic lateral sclerosis (ALS), also known as Lou Gehrig's disease and popularized contemporaneously by its most prominent survivor, Stephen Hawking.  ALS is a devastating neurodegenerative disease impacting the brain and spinal cord; one that routinely progresses to paralysis and death, and for which there is no effective drug treatment. 

Mr. Ko, by relying on what is presumably a very emotional response from those concerned and/or impacted by ALS, has waged an effective social media "war" against the FDA, typically painting them as the bad guys, for their apparent lack of response to Genervon's "application" (it's more a public request) for rapid approval of GM604. That social media war has garnered some 500,000 signatures to date which underlines the effectiveness of such media initiatives quite convincingly. The FDA had until recently issued no response, which is how it has to be by law, in that they do not make public comments about drugs in the process of review, which remains the remit of the companies involved. 

What really got the news item buzzing was firstly a review of the data Genervon obtained from 8 patients by Steve Perrin, President & CSO of the ALS Therapy Development Institute, which raised serious concerns about the claims being made by Genervon. Secondly, and this really stirred the pot, was the rumour circulating that Genervon had not even submitted an application to the FDA - that "application" being at the centre of their beratement of the FDA! This was robustly quashed by Winston Ko, who claimed that they had filed an application with the FDA, earlier this year, and that the agency had missed its deadline for a response. 

The repeated claims that the FDA had missed its 30-60 day deadline in mid-April, coupled with Steve Perrin's review, prompted an extraordinary move by the FDA who asked for immediate publication of the data that Ko is touting as the foundation of a new miracle cure for not only ALS, but for other CNS diseases as well. The FDA demand to see the data in question was a huge calling of Ko's bluff, and one that seemed to carry some gravity not only for Ko, but for the entire Genervon organization. 

Ko has shamelessly promoted the naturally occurring GM604 peptide as a "master regulator of the nervous system", and one can only imagine the probably false hope that such statements invoke in those living and dying with the ravaging symptoms of ALS. This highly unusual move by the FDA emphasised that the FDA had no information at hand on this drug candidate, at all, which forced Genervon to concede that they were merely "communicating" with the FDA about them accepting their application - a very different thing from having applied, months ago.

It all reeks of desperation on the part of Genervon, if not simply of Ko himself, who may well be trying to salvage his own position in the face of a fierce board breathing down his neck - then again, in a move reminiscent of Jamie Dimon of JPMorgan Chase, Mr. Ko is both CEO and President of the Board - so he is clearly in an extremely powerful position to pursue a single-minded agenda and do things his way. But leaning heavily on the sick and the dying, and using their weight to apply a form of social pressure on the FDA for an "application" that was never even submitted, is a risky move and one that is likely going to bite him back. 

One wonders how the owners of those 500,000 signatures feel today upon learning that the petition they signed was based on false claims that the FDA had been remiss in dealing with review of this new wonder drug that could bring hope to many? Genervon may feel the full weight of those 500,000 individuals turning against them, in the end. And the FDA? Well, they are hardly known as touchy-feely at the best of times, so what are the chances of any lightning-fast reviews or rapid-fire approvals now? 

I would say we have more chance of hearing that the FDA is having an open day barbecue for the public, than that. Ah, social media, powerful little self-promotion engines that work very well when handled by an experienced driver, but those engines can backfire loudly when they are mistreated or used for disinformation purposes. Let's just hope that new hope for those suffering from ALS comes from another source, and soon!