R&D | Pharma Strategy Blog

Red and Green Flags in cancer research and development

By MaverickNY on January 24, 2014

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.

My perspective is a little different, coming from multiple angles of science and academia, industry, consulting, and as blogger on cancer research and development both here and on our sister site, Biotech Strategy Blog.

A few people asked me what my thoughts on biotechs were and what my 5 red flags might be, but back then we were in the middle of the launch of our new conference coverage service and planning for the last round of medical meetings on the oncology circuit.

My side comes from an oncology/hematology/immunology background and may not be broadly applicable outside those specialist fields. Without further ado, here are things I tend to consider when evaluating companies in this space, whether that be as an analyst, consultant, investor, blogger or whatever hat is on that day:

1. Is the target oncogenic?

This sounds obvious, after all, how can you hit a target you don’t have or know about? As Dr Len Saltz lucidly explained it well here – companies who ignore the basics are doomed to failure. In the world of targeted therapies, this is probably key. If it doesn’t matter to the survival of the tumour, then the chances are efficacy will be poor and all you add are unwanted side effects.

There are numerous examples from the difference in targeting BRAF vs. BRAFV600E in metastatic melanoma to pan PI3K vs. PI3K delta in CLL and NHL, and many many others.

Basically, a mutated target is more likely to matter than mere overexpression or amplification of target, nebulous targets are much harder to pin down and increase the chances of failure.

Another related red flag is completely misunderstanding the disease being studied. You can tell when companies make this mistake easily, because they tend to lump multiple different subtypes into one trial. Not only do various tumour types behave differently, but various subsets can also behave in different ways – some are chemosensitive, others not, some respond to targeted agents, some don’t. An excellent example is soft tissue sarcomas (STS), where each subset can be treated as individual diseases; doing a catch-all trial here is a huge red flag as it is usually doomed to failure. A much smarter approach is isolate key oncogenic targets and select patients or subsets most likely to respond to the targeted therapy being investigated.

Solution: Validate the specific target early, before you run large phase III trials.

2. Is the science solid?

We’ve all sat through small cap biotech presentations that bamboozles with fancy science and dare I say it – fervour. Except that the subsets the agent appears to work in appear to be odd, at best. Lack of a validated biomarker or target is another red flag, as are catch-all studies. After all, why would you want to treat a so-called targeted drug in an untargeted fashion? Often, these approaches portend negative overall trial responses and retrospective frantic data mining for a subset that explains the few responders.

Related to the ‘right target’ is something called therapeutic index – that is, are we shutting down other relevant pathways to reduce resistance? All too often, a small company has only one drug and no broad pipeline to add and combine modalities to achieve this. That makes it harder to compete unless they license the agent or get bought out by a bigger company with another drug to partner with it. The solid science argument might therefore apply to a logical combination rather than monotherapy – the company that refuses to see this is likely to experience a few challenges along the way.

Another red flag is the use of old fashioned preclinical models that have no relevance to modern research. It happens more often than many realise. Even worse is the paucity of relevant preclinical research and then having to do the work after a spectacular phase 3 trial failure, when thoroughness of the research before the trials would have saved a lot of pain, angst and even embarrassment.

Solution: Best to do the biomarker and validation work in preclinical and phase I/II, then run prospective trials based on more stringent patient selection criteria to improve your chances of success. You are often better off running multiple phase II trials to keep refining and honing the approach and combinations with greater degrees of certainty than rush into expensive randomized studies and failing badly. Companies that do these two things well offer clear green flags to biotech watchers.

3. Does the phase I and II investigator pool include relevant researchers e.g. translational scientists or immunologists?

Many will be surprised how many ‘targeted’ agents involve clinical trials with clinicians who are not scientists, or worse, come from the chemotherapy world. Dovetail this with the catch-all approach from #2 and you have a recipe for disaster before you begin. Even big pharma can fall into this trap.

These seemingly random approaches tend to met with vague quotes from thought leaders, “It’s well worth trying” or “I think it’s a good idea” without any precise rationale for why the concept will work. These doctors are easy to spot in press briefings – they look like a deer in the headlights when pressed with detailed scientific questions and run a mile from being interviewed afterwards, unless it’s for the kind of benign potted quotes mentioned above. Not a good sign.

4) Is it a good company?

There are some biotech and pharma companies who unfortunately have a string of failures behind them. The uninitiated often dismiss this, citing the Thomas Edison example of many tries before finally achieving success. You could also argue that maybe, just perhaps, they keep making the same fundamental mistakes outlined above and haven’t learned to adapt.

Other flags here are openness and transparency, or rather the lack of it. This includes selective disclosure and hyping of efficacy claims while understating the adverse event profile. Research and being on top of the data will stand many in good stead here, whether from a licensing, competitive analysis or investment standpoint.

Just as David Sable mentioned one of his red flags was being disrespected, for example by the company person who sits in his seat at the head of the table, there are similar parallels on the other side:

Good companies tend to be open, accessible and transparent, in my experience. They routinely offer or provide access to their scientists, researchers and thought leaders doing the work when asked. They don’t exclude you from briefings: “No, because you’re merely a science blogger.” Ouch yes, been there done that!

5) Does the company/drug offer value?

There is no doubt that being first to market offers a competitive advantage and later drugs may need to provide superior efficacy or tolerability, but if you are looking at 5/6/7th to market, you have to question what is the real value add going to be?

Companies who just happen to have a me-too and no clue how or where their drug will add value over the ones before them are notable red flags. Incremental improvement in outcomes is one thing, same old, same old is quite another. Future revenue success is driven by having a clear path to market and a good value proposition that is compelling. Without these, any clinical R&D is largely wasted time and effort, not to mention a significant expense. Being aware of changes in the competitive landscape as well as flexible in adjusting to them is also critical. Look at how many companies have been caught surprised and flat footed by the rise of immuno-oncology, for example.

On the other side are those companies who are smart and innovative; they position the product creatively, whether it be in the form of a combination with another agent that overcomes resistance or delays the resistance thus improving survival for patients add clear value. Another way to create more value is that the drug can work in a slightly different way from what went before e.g. it hits a more relevant oncogenic target creating a well defined patient segment and path to market (see #1) or has fewer off-target effects, thereby improving tolerability.

It’s not all bad news and red flags in oncology R&D

Green flags include innovative, successful companies with a demonstrable track record of launches and drugs that make a difference to patients lives. There’s no mystery why Roche/Genentech and Novartis consistently stand out from the pack in oncology/hematology – they have a relentless mentality to innovation and value creation as well designed, scientific based trials. BMS have done very well transforming their oncology franchise from chemotherapies that hit the patent cliff to being a leader in immune-oncology with their acquisition of Medarex and partnerships with biotech companies such as Innate Pharma for licensing deals.

It’s up to the rest of the pack to innovate better and faster if they want to catch them up.

Resources:

Luke Timmerman’s 21 Red flags for biotechs

David Sable’s Red Flags and Green Flags

Katrine Bosley’s Red and Green Flags

Andrew Goodwin’s Red and Green Flags

2 Comments

Time to rethink cancer clinical trials strategy?

By MaverickNY on November 27, 2012

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:

“The phase I trial is designed as a dose-escalation study to determine the maximum tolerable dosage (MTD), that is, the maximum dose associated with an acceptable level of dose-limiting toxicity (DLT – usually defined to be grade 3 or above toxicity, excepting grade 3 neutropenia unaccompanied by either fever or infection.”

What usually happens afterwards in cancer research is that the RP2D or Recommended Phase II Dose is suggested, often just a bit under the MTD.

The idea behind this is to maximise the efficacy, since after all, that’s what we’re aiming to achieve in the large scale phase III trials viz improved survival, whether it be progression-free survival (PFS) or overall survival (OS). PFS defines the time elapsed before symptoms worsen, while OS tells us whether people are living longer or not based on the therapeutic intervention.

But recently over the Thanksgiving Holiday I was reading Tim Ferriss’s “The 4 Hour Workbook” where he discussed the concept of ‘minimally effective dose’ or MED in the context of exercise and workouts. This lead me to wonder if this is something we should consider in oncology clinical trials – would the Pareto 80:20 principle work here too?

In other words, instead of seeking the MTD should we actually test for the MED and have less toxic side effects in the process? This potentially would also lead to better adherence and may even improve overall survival.

You probably think I’m nuts at this point, but hear me out.

Physicians and Pharma companies often forget that in the real world, patients fail to comply with oral cancer medications due to intolerable side effects that make their lives miserable. Not everyone is young, fit and healthy with an excellent performance status – multiple regimens and prior chemotherapy can really take it out of you, leaving you wiped out to face the next round. Even tyrosine kinase inhibitors (TKIs) are not always a piece of cake to take. The constant niggly, but low volume side effects, can wear anyone down.

In support of this argument, let’s look at the impact of adherence on survival. I remember listening to David Marin from the Hammersmith present their findings on CML and compliance at EHA last summer. They observed that if adherence was less that 90%, then survival was dramatically impacted. You can see the difference in the curves on Biotech Strategy Blog. It still vividly sticks in my mind 18 months on!

What’s also fascinating, is that in Rubinstein and Simon’s document, they also discuss the idea of “Finding the Minimum Active Dose” as shown in the table below, although I have never seen anyone discuss this in all the cancer conferences I have been to over the last 20 years!

Thus, if we were to reconsider the whole concept of higher dosing in favour of minimally effective dosing, then we might actually see better adherence and compliance on a broad scale and therefore, better outcomes for more people.

If we then add in the growing trend to combine two TKIs or a TKI and monoclonal, whether approved or as a novel-novel combination, a fresh approach to testing drug combinations rather than different MTDs starts to look more appealing.

Just a thought.

4 Comments

Highlights of AACR 2012 – Part 2

By MaverickNY on April 18, 2012

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.

Reuben Sierra, Ming Tsao's Lab (with permission)

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.

Why?

Well, at the ECCO meeting in Stockholm last September, Tom Lynch was discussing the role of one such EGFR therapy, cetuximab (Erbitux), in lung cancer and wearily declared prior to presenting a negative study,

“If ever there was a drug desperately needing a biomarker, it’s cetuximab”

because while some of the patients responded beautifully to the drug, many others didn’t and at that time, there was no way to determine upfront who might respond before treating.

This is clearly a waste of valuable resources and time because catch-all studies mean that the number of negative responses can balance out the positive responses in too heterogeneous a population. That said, if you know what the potential target(s) or biomarker of response are, then you can select patients more precisely for a study and improve the subsequent overall response rates and OS advantage dramatically.

As Sierra et al., pointed out in their poster at AACR, we do know that:

“Patients that present amplification or activating mutations (L878R or exon 19 deletions) of EGFR, have higher response rates. Selection improved response rates from less than 10% to over 60–80%.”

This is very good progress, but how did their research take this concept further?

In this study, the group reported the preliminary findings from a complex study of genome-wide screenings on EGFR resistant cells to try and identify new genes that might mediate resistance and, importantly, be potentially druggable, unlike say, MYC. This would then offer new logical targets for combination therapies to be tested in the clinic in patients to determine if outcomes could be improved.

At the time of the poster presentation, the group had indeed identified a short list of potential candidates (not named as this would be available in a later publication). Conceptually though, this was an elegant study and I really liked the concept.

This morning, I was delighted to see a news snippet from the 3rd European Lung Cancer Conference in Geneva, Switzerland where the ESMO press release noted that Dr Tsao’s group performed:

“An exploratory analysis on the TORCH patient tumor samples that were available for analysis, looking for molecular biomarkers known to be potential predictors of benefit from EGFR inhibitors.”

Despite the biomarker analysis being pre-planned, however, only a third (36%) of samples were available for analysis. It is always harder to do retrospective mutation analysis on small sample sizes unless rigorously collected as per the BATTLE trials.

I’m looking forward to hearing what targets were identified in Drs Sierra and Ming’s research once published or presented in more detail at a future conference, as this may help us move the field forward in terms of rational combinations to either overcome resistance to EGFR therapy (other than the well known T790M mutation) or prevent resistance from developing early.

Now, that would be very cool and I do hope they alert us to the publication in due course – watch this space!

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Highlights of AACR 2012 – Part 1

By MaverickNY on April 17, 2012

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.

It was clear from discussions with numerous new product people that while pipeline boards are starting to look a little healthier than of late, many of the new compounds are not yet public, but effort are being made to expedite these into the clinic too. Roche and Novartis have dominated the oncology landscape of the last few years but there were signs of resurgence from old stalwarts such as GSK, Lilly, Pfizer, Amgen and Merck. Such fierce competition is good to see.

Posters from Day 2 at AACR...

The small biotechs were also showcasing some interesting data and over the rest of this week, I’ll be highlighting some of the ones I liked and also explaining some of the new targets and biomarkers that caught my eye.

There was, however, a noticeable dearth of handouts and QR codes (for the PDFs) in the poster sessions this year, necessitating more requests for copies by email, hence the delay in covering the highlights post conference.

I’m pleased to say, however, that many presenters generously shared their poster offline and some of these will be discussed later this week.

Here are some of the topics I’m going to be covering in more detail:

Update on the PI3K-AKT-mTOR and RAS-RAF-MEK pathways
New targeted agents in late preclinical and phase I development
Review of the Science Policy session on regulatory and clinical challenges in new drug approvals
Update on new approaches in colorectal, prostate and lung cancers

Check back PSB daily this week for more detailed analyses and insights…

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Some thoughts on cancer research and the pipeline cliff…

By MaverickNY on June 28, 2011

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.”
Christiane also quoted Viehbacher, “Still not enough of bright science making its way to patient benefit.”

The last point particularly made me wonder, because quite a few oncology companies have broad and deep pipelines, often with more compounds than they can possibly advance at once. Even big Pharma or Biotech has to rationalise resources, budgets and people or nothing would get done.

How do those decisions get made?

Some are smart at life cycle management (GSK and Roche spring to mind), some think strategically about their portfolios, others get mired down in politics or – even worse – distracted by numerous committees focusing on what I call ‘fluffy puffy’ abstract things instead of moving the compounds rapidly through the pipeline to become safe and effective drugs that make a difference to patients lives.

The future of successful cancer drug development is likely going rest heavily on investment in basic science, molecular biomarkers and diagnostics, and novel-novel clinical trials that target multiple aberrations driving the disease.

Investors aren’t interested in any of these things, though; most just want a rapid or high return on their investment. Spending less on R&D is much more in tune with their short term thinking:

Viebacher: If you sit down with investors, they clamor to stop spending on R&D, just do a buyback. #BIO2011

Tweet from Christiane True (PharmaLive) at BIO

The thing is, if pharma companies are going to rely on buying or licensing late stage compounds from Biotech, there is only so much small to medium Biotechs will be able to do going forward, because the future will mean more diagnostics and biomarkers, which are very expensive in cancer research, and in some cases, prohibitively so. This will require closer, earlier collaboration with Academia and even different types of trials thanwe have been used to in the old chemotherapy world.

There are sometimes more challenges with clinical trial designs in small biotechs going from phase II to III, as Sanofi discovered with BiPar and iniparib and Novartis with Antisoma and ASA-404. If we want to reduce the number of phase III failures, we have to get smarter about more iterative studies in phase II, better patient selection, incorporation of biomarkers, more logical combinations and yes, all of these will cost more dollars that will likely give investors insomnia.

Finding out more about the compound earlier will be the new name of the game – it is obviously better to abandon a weak agent on phase I or II than expensive phase III trials.

In the end, the companies who will win out in the long run are often those who think strategically, drive innovation, focus on science-based research, license earlier rather than later, invest in biomarker/diagnostic research, work in close knit cross-functional collaborative groups, avoid the twin pitfalls of bad karma and politics and ultimately ‘see’ things more clearly than the pack allows them to translate that into meaningful action.

It occurred to me that if you have to ask who the KOLs and experts are, then you have a long way to go and that doesn’t inspire confidence in the agent you’re developing. If you have too much greed in the boardroom C-level that’s clearly going to hamper things as well, especially if they want to implement cuts down the line. All of these myriad of factors surprisingly do matter when it comes to riding out patent cliffs and maintaining R&D momentum.

I should probably add ‘corporately ignore the short term investors for long term solid gains,’ but that would be a bit cheeky, perhaps 😉

Ultimately, what I would really like to see is less talk and more effective action:

A lot of talk about benefits and challenges with personalised healthcare but no mention of solutions #BIO2011

Tweet from Pieter Droppert in the Personalised Medicine session at BIO

I guess that’s why the American Association for Cancer Research (AACR) remains my favourite meeting in the annual conference calendar – at least Academic attendees are presenting data and discussing solutions in informal chats in corridors or poster sessions on how to address the practical issues of improving cancer research. Inevitably, the smart companies are tapping into this resource and working alongside each other to unravel the complex mysteries.

On the future of cancer treatment and research

By MaverickNY on June 27, 2011

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:

For those of you interested in my perspectives on some of the early clinical trial approaches, there’s a guest blog post on PharmaLive’s R&D Directions entitled “ASCO followup: Patients, pathways, progress in practice” today – check it out!

Accelerated approval and cancer drugs

By MaverickNY on March 24, 2011

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.”

The author argues that:

“Phase 3 trials are expensive and time-consuming, usually taking at least 2 to 3 years to reach survival end points. The news of a highly successful new compound in phase 1 or 2 rapidly reaches physicians and patients, creating demand for early access.”

While we have seen some successes with the Accelerated Review process with imatinib (Gleevec), erlotinib (Tarceva), cetuximab (Erbitux), bevacizumab (Avastin) and others, there has also been a flood of promising phase II agents that duly flopped in randomised phase III trials, with Pfizer’s figitumumab, Novartis/Antisoma’s ASA404 and sanofi-aventis’ iniparib to name a few off the top of my head.

One of the challenges here is that companies often take a targeted therapy but strangely test it in an unselected patient population, which will increase the chances of failure in a more rigorous randomised phase III trial. In an ideal world, several carefully designed adaptive phase II trials would help develop logical combinations and markers of response, thus increasing the chances of success in phase III studies.

The big problem as I see it then, is that while we have exciting new agents likely to be approved in 2011 such as:

crizotinib in lung cancer
ipilimumab (Yervoy) and PLX4032 (vemurafenib) in metastatic melanoma
brentuximab vedotin in Hodgkin Lymphoma
abiraterone acetate (Zytiga) in prostate cancer

we don’t always know how to carefully select patients to enable treatment based on the underlying molecular basis of the disease.

Of those mentioned above, with crizotinib (ALK), vemurafenib (V600E BRAF) and brentuximab (CD30) we clearly do, but with abiraterone and ipilimumab the issue of patient selection seems less clear at the moment. Sadly there are not any biomarkers available to tell us which patients are most likely to benefit from treatment in targeted therapies already approved such as bevacizumab.

The fate of bevacizumab in breast cancer has yet to be determined. It was approved under the FDA Accelerated Review process based on the initial phase II data, with the assumption that the phase III trials would show an improvement in overall survival. The AVADO and RIBBON1 trials showed a benefit in progression free survival or PFS (ie a surrogate marker of event free survival), but unfortunately were not positive for overall survival, which is the ultimate measure of disease progression and the condition required to be met under the fast track process.

The FDA are therefore recommending withdrawal based on the lack of overall survival as per the accelerated agreement and Roche offering the counter argument that there was evidence of patient benefit. That issue will no doubt continue to be debated for much of 2011 until the public hearing later this year. There is an excellent analysis of the impact of the FDA recommendation on bevacizumab uptake in the US in Oncology Business Review for anyone interested in trends.

Ultimately, we need have a better understanding of the molecular basis of the cancer types and drugs developed to target that aberration in a more carefully selected patient population. The arguments for and against accelerated review will run and run – probably for longer than the debate about how to pronounce some of the new names!

My position on the accelerated review process?

When it works, it works well. However, problems can arise when you get phase III trials that do not support the full approval due to a lack of a proven overall survival advantage in the population evaluated. The FDA can find themselves in an impossible position especially given the high emotions that run in breast cancer, for example. The onus should be on the company to do further research or trials better defining the patients who are most likely to respond rather than risk exposing thousands of patients to the systemic effects of a drug that may not offer meaningful benefit to the majority.

References:

Chabner, B. (2011). Early Accelerated Approval for Highly Targeted Cancer Drugs New England Journal of Medicine, 364 (12), 1087-1089 DOI: 10.1056/NEJMp1100548

3 Comments

On cricket and cancer research…

By MaverickNY on March 9, 2011

“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.

England v Ireland in the 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!

Ugh, such is life – all good Englishmen will no doubt down another pint and shake their head in sorrow.

Still, that metaphor got me thinking. In sports, there’s always another game, another tournament, another year – life goes on regardless. While I was growing up, the mighty West Indies were at the height of their scintillating dynasty. Now? Not so much. Yesterday’s champs are tomorrow’s chumps and vice versa. In clinical R&D though, if a major trial flops or is negative, it is rare that a company will go back and reconsider another series of trials with the agent in the same tumour type, even if the trial design was flawed, unless they have others already ongoing or in very late stages of planning.

You get one shot to get right. Maybe two, if you are lucky.

Moving forwards, the incredibly high rate and cost of failures is unsustainable. In the oncology arena, I think we will see the smart companies get smarter about drug development. What does this mean in practice?

More exploratory, smaller, phase II trials
Focus on pathways and related activities as targets
Increased use of translational research in 1) to determine mechanisms of resistance, adaptive pathways, biomarkers, logical combinations
Greater use of the adaptive trial design to find the best winning combinations
Increased use of diagnostics and biomarkers to select more clearly defined patient populations (ie smaller subgroups)

These trends are slowly happening now, you can see it more clearly in some pathways such as PI3K-mTOR, for example. The days of taking a targeted therapy and adding it to standard of care chemotherapy in an unselected population, as happened with iniparib in triple negative breast cancer, are unlikely to be the future of cancer research.

What the more intense integration and iteration of basic research and phase II trials will give us is perhaps, a slightly slower development process, but with a much higher chance of success. In my book, that’s a much better approach – cancer patients deserve the best shot we can give them.

Photo Credit: ICC World Cup

Aside: For those wondering, my pre tournament tip was that India would be very strong contenders for this year’s World Cup, if only their bowling manages to get organised. Their batting strength is second to none, but Pakistan have a good chance if the Indian bowling shows any chinks and cracks. Cricket is a team game, after all. England regrouped and recovered to beat the strong Springboks from South Africa, so all is not lost yet! Anybody but the Aussies, that’s all that matters 😉

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Sisyphus, oncology R&D and Pharma

By MaverickNY on September 15, 2010

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.

After all, that's what we all live for – the few that make it to market and make a real difference to the lives of people with cancer.

Celebrate Sisyphus today – it's not the fancy silver lures or cool new toys that makes the difference in the end, but the steadfast daily grind through R&D that eventually pays off big time for everyone.

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Life is an adventure

By MaverickNY on August 24, 2010

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?

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