Recently, there was a red flags meme going around the biosphere started by Xconomy’s Luke Timmerman on 21 Red Flags in Biotechs to Ignore at your Peril. This inspired excellent contributions from David Sable on the buy side with his red and green flags, as well as Katrine Bosley from the Biotech CEO’s perspective and Andrew Goodwin on the research and investor side. They are all excellent reads so if you missed this wonderful collection, please do check them all out. If anyone wants to add new ones, please highlight them in the Comments below.
Recently, I’ve been pondering clinical trial design and wondering whether there is better way to do things, since much of the current concepts were based on cytotoxics that often had a very narrow therapeutic window. With the advent of oral tyrosine kinase inhibitors (TKIs), the model seems, well, a bit old and tired and doesn’t always help us develop the optimum outcome.
In phase I oncology clinical trials, for example, we seek to find the MTD, as explained by Drs Rubenstein and Simon (PDF download) at the NCI:
Yesterday, I mentioned that some of the best bits of this year’s American Association for Cancer Research (AACR) meeting were the numerous gems in the poster sessions.
One of the coolest such posters I came across was from Ming Tsao’s group.
Specifically, Rafael Sierra (see photo right) was hosting an excellent piece of research entitled: “Overcoming resistance to EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer.”
This is an area of much needed research and breakthroughs.
The 2012 American Association for Cancer Research (AACR) meeting in Chicago was interesting for several reasons. While there were no truly ground breaking data such as in previous years as with, for example:
- vemurafenib in BRAFV600E melanoma
- vismodegib in basal cell carcinoma (BCC)
- crizotinib in ALK+ lung cancer
there were a lot of encouraging signs for the future.
What made the meeting exciting for me was the sheer number of new compounds emerging from late preclinical to early phase I – clearly companies are looking to restock their pipelines with the threat of major patent cliffs imminent. Not everyone is chasing new compounds to license in! The sheer breadth and depth of the pathways targeted by the new compounds took me a little by surprise.
This morning I was pondering a triangulation of several random thoughts that appeared in my Twitter stream, many from BIO, about various topics:
- Discussing the patent cliffs and lack of revenue generation some companies such as Lilly will no doubt be facing with John Carroll (Fierce Biotech) and Matt Herper (Forbes Health)
- Christiane True (PharmaLive) at the annual BIO meeting quoted a speaker as saying “doing more with less” which seems pretty much de rigeur these days
- Ron Leuty tweeted a quote from Chris Viehbacher’s (Sanofi) presentation at BIO, “Not doing more with less, but doing different things.”
This week I’m preparing an in depth mini series on the molecular target landscape associated with prostate cancer, which will be scheduled for next week, so do check back if that is a topic of interest to you.
In the meantime, I came across this video from MD Anderson, where the new President-elect Dr Ronald DePinho talks about the near term future of cancer research and where he thinks we will be going.
It’s less than four minutes long, easily understandable and well worth watching:
There is a provocative article in this week’s New England Journal of Medicine asking whether the accelerated approval process should be used for more cancer drugs:
“The striking results of recent phase 1 trials of targeted cancer drugs have provoked serious discussion about shortening the road to drug approval.”
The main thrust of the argument was that it takes on average seven years from entering human trials to approval if phase III trials are included in the oncology drug development process.
“Of the 23 oncologic drugs given accelerated approval between 1993 and 2008, two were ultimately withdrawn from the U.S. market — gemtuzumab because of toxicity and gefitinib because of lack of efficacy.”
“How the mighty have fallen so quickly. England were national heroes after winning the Ashes. Now they are national chumps after this shocking and embarrassing defeat.”
Geoffrey Boycott, on England’s surprise defeat by Ireland in Cricket World Cup.
Some of you readers will be aware that I’m a big sports fan, of cricket and football in particular, so my cheerful mood earlier this morning was somewhat muted after learning that the motherland, England, somehow managed to lose to lowly Ireland. In cricket!
Loved this cartoon from Hugh Macleod at Gaping Void that just arrived in my mail box:
Source: Gaping Void
In many ways, this is what drug development can look like on a day to day basis. Scientists repeating experiments, project teams holding endless meetings etc, that sometimes it's hard to see which in a portfolio of agents might actually make it through to market and which will fail along the journey.
Still, eventually, some of those small rocks reach enough critical mass (data) and actually do tip over the edge to be successfully commercialised.
Regular readers will know that I'm a big fan of Gaping Void cartoons by Hugh Macleod.
This one really resonated:
Source: Hugh Macleod, Gaping Void
If you think about it, Pharma R&D is also a bit of an adventure (or even a roller coaster sometimes); you never know quite whether you're on a winner or a loser with company pipelines and portfolios.
Attitude also comes into it – do you live by paycheck or project, or do you truly love what you do?