Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Pharma innovation’

As we herald in a New Year, it is time to reflect a little on the past year. 2012 was, to paraphrase Professor Bertrand Tombal’s quote about prostate cancer drug development, “a Grand Cru year” for the United States Food & Drug Administration (FDA) with 39 new molecular entitites (NMEs) approved. This is the highest approval number in the last 10 years, beating the previous high of 36 obtained in 2004. Reuters report it is a 16 year high.FDA 2012 New Molecular Entity NME Approvals Biotech Strategy Blog

Unfortunately, I don’t think can we can draw many conclusions about the state of drug development innovation from this 2012 high.

The FDA in their 2011 report on novel new drugs note that “the number of NMEs approved over time has not been substantially increasing.”

To me, the overall picture looks pretty flat. There’s bound to be variation between years as a result of timing differences with some regulatory submissions obtaining priority review, while others do not.  Some companies can take longer than others to close a clinical trial database and prepare a dossier.  We also have to factor in that some clinical trials may end earlier than expected, if the data is positive.

Regulatory approval is the result of innovation that started several years ago. It only represents the point at which you have a safe and efficaceous product that can be sold to the public. The number of approvals in any given year is not a surrogate benchmark for the state of current innovation.

Given it typically takes several years to bring a new product to market, what we are looking at today is the result of research done 5-10 years ago. It is, however, interesting to note that of the 39 NME approvals in 2012, one-third (13) were cancer related.FDA 2012 Cancer Related Approvals Biotech Strategy Blog

A key driver of innovation in this area is the increased knowledge we have of cancer biology.

In my view, investors will continue to support companies that develop new products with:

  • a clear scientific rationale as to why their mechanism of action may impact the disease
  • a focused clinical development plan that through use of biomarkers and diagnostics targets those most likely to respond
  • a market opportunity worth going after in what is increasingly a competitive landscape

2012 was a “grand cru year” for the FDA. I look forward to what 2013 may bring and to learning more about the new products in development that may make a difference to the lives of patients.

Happy New Year!

 

According to a forthcoming article published in Forbes, excerpts of which appear on Matthew Herper’s blog “The Medicine Show,” big pharma should take bigger risks and outsource R&D to smaller, innovative companies.

At least that’s the philosophy of Bernard Munos, the former Lilly sales executive who has focused on the innovation problems faced by the pharmaceutical industry. According to Forbes, he believes that big pharma should “cut research and development” and “rather than do research in house, companies should close their labs and outsource the work to tiny, nimble startups that can explore bigger, crazier ideas.”

However, as Munos goes on to say in an excerpt published by Matthew Herper:

“You cannot script innovation,” Munos says. “You cannot boil it down to a code of best practices. Because it is unpredictable and the opportunities in science do not match the opportunities in markets.”

That is why Munos’ strategy of outsourcing drug discovery may not be the right one – there is no formula that you can give a vendor on how to be innovative.  Indeed, leveraging the innovation of small biotechnology companies is nothing new – isn’t that what big pharma already does with its licensing deals and alliances?

The question that comes to mind from the provocative Forbes article is whether innovation of drug development is a service like clinical trials that can be outsourced? Contract Research Organizations (CRO) are now the route by which the majority of companies conduct clinical research. They possess the efficiency and economies of scale to do what is a mundane, process driven task of setting-up, monitoring and processing data associated with a clinical trial on a global basis.  Those models works reasonably well and are now the norm.  Standard Operating Procedures (SOPs) exist for everything a CRO does in what is a heavily regulated process of gathering data for regulatory submissions.

Is this the same for drug discovery? I am not so sure.  Firstly, if you outsource you have to give direction. You have to have a commercial or scientific target, and resources have to be allocated accordingly. Who decides where R&D investment should be spent? Ultimately in any outsourced venture, the company spending the money makes that decision.  So all you are doing is shifting the execution of the task, not the development of the strategy, which is where the innovation needs to take place.

Indeed, if one looks at the clinical trial service model, what has happened is that consolidation of small and medium size CRO’s continues to take place.  Small companies simply lack the resources to get the job done. I am not convinced that small is necessarily best when it comes to drug discovery.

What’s more, Munos, in the recent Science Translational Medicine (STM) commentary on innovation that he wrote with William Chin, appears to argue for a different model than the one he proposes in Forbes.  He states that:

“pharmaceutical companies cannot mitigate risk adequately by pursuing “safe” incremental innovation, instead the industry should reengage in high risk discovery research on a broad scale and only take genuine breakthroughs to the clinic.”

This is easy to say in practice, and may not be a realistic strategy when there is money and sales to be made from me-too and follow-on compounds. How many companies are going to say we are not going to continue with this business model?

According to Munos in Science Translational Medicine (STM) the options open to big pharma are to:

  • Participate more decisively in collaborative networks
  • Form precompetitive consortia and other partnerships to share costs
  • Adopt new research models such as public-private partnerships

To me, there seems to be a disconnect between what Munos says in the Forbes article and what he says in his STM commentary.  If he has a clear vision for the future of pharma innovation, he should at least be consistent.

Where I do agree with Munos is the conclusion of his STM commentary that success starts with breakthrough science. This message was also clearly stated at BIO 2011 by the panel on innovation that included GSK’s Moncef Slaoui.

Pharma R&D $ needs to be spent more wisely. In my opinion there is a role for incremental, as well as breakthrough, innovation. The two are not mutually exclusive.

Is cutting R&D and outsourcing discovery the route to success as Munos suggests in Forbes?  Only time will tell as pharma R&D retools and refocuses for the future.

ResearchBlogging.orgMunos, B., & Chin, W. (2011). How to Revive Breakthrough Innovation in the Pharmaceutical Industry Science Translational Medicine, 3 (89), 89-89 DOI: 10.1126/scitranslmed.3002273

Innovation involves insight that allows you to see around the corners. That’s the perspective according to Andrew Marks, Professor of Physiology & Cellular Biophysics at Columbia University Medical Center, who recently wrote a Commentary on Innovation in Science Translational Medicine.

Entitled “Repaving the Road to Biomedical Innovation Through Academia”, Professor Marks’ commentary captures the reader’s attention in the first sentence:

“The path to biomedical innovation requires a synthesis of seemingly unrelated observations.”

He goes on to say, “innovation requires joining the pieces to solve the puzzle.”

Innovation according to Marks is difficult to define, something I also noticed at BIO 2011 in the industry panel that I attended.

However, like pornography, “we know it when we see it” to paraphrase Justice Potter. Mark gives examples of innovation in the biological sciences: germ theory of disease by Lister, discovery of antibiotics exemplified by Fleming, Watson & Crick’s work on the structure of DNA.

I don’t disagree that these are examples of paradigm shifting scientific discovery fueled in some cases by serendipity. But are they the best examples of innovation in the biological sciences? Has nothing innovative happened in the past 50 years that is worth mentioning?

In his commentary, Marks goes on to outline the reasons he thinks biomedical research is threatened in the current environment. This includes the standard litany of woes expressed by many academics today:

  • increased costs
  • insufficient support
  • limited industry support
  • prolonged postdoctoral training
  • limited opportunities for research careers in academic medicine

Interestingly, however, he suggests that part of the fault for this lies with academia.

Academia and the National Institutes of Health (NIH) have failed to evolve with the times, he writes. They “have been guilty of a lack of innovation” in how they support science.

Today’s challenge according to Marks is the need to balance revolutionary research that is innovative with incremental research necessary to further knowledge.

Marks goes on to say that the NIH is not well equipped to judge innovative groundbreaking research.  Moreover, “the unwritten rule, often said tongue in cheek, is that when applying for NIH funding one should only propose experiments that one has already done and for which one can show convincing preliminary data.”

The solution he proposes is to change the way federal funding of biomedical research takes place. The NIH should divert to industry the costs of clinical trials and establish distinct funding mechanisms for high-risk research. I am not sure I agree with this, as many clinical trials would not be funded by industry and translational research is not just about basic science, but is from bench to bedside.

The solution proposed by Marks also predisposes that you can properly assess and judge innovative research when you see it.  This is not as easy as it seems. As Marks points out:

“NIH likely would not have funded proposals to test the germ-theory, antibiotic-action, or DNA double–helix hypotheses because these projects either would have been deemed too risky (that is, they have a low likelihood of success) or too speculative (lacking in sufficient “preliminary data”) or because the approach would have been criticized as being misguided.”

Instead of looking for new ways to fund basic science, Marks proposes a rework of the way NIH funds research.  Cutting the same cake in a different way is unlikely to solve the fundamental problem: there is simply not enough government funding to go around. In the face of the US budget deficit, it is hard to imagine a significant increase in NIH funding to create new funding opportunities.

Would a more innovative approach be to ask academics to rethink how research is funded in their institutions?  Focusing on the NIH and Federal Government funding is not the optimal solution in my opinion.

Marks is right in that Academia needs to innovate how science is supported. Incremental change of the way NIH funding takes place may fill in some potholes, but will not repave the road to biomedical innovation.

ResearchBlogging.orgMarks, A. (2011). Repaving the Road to Biomedical Innovation Through Academia Science Translational Medicine, 3 (89), 89-89 DOI: 10.1126/scitranslmed.3002223

Science Translational Medicine June 29, 2011 Cover based on Rodin's The ThinkerWith an image of Rodin’s bronze “The Thinker” on its cover suggesting deep thought and insight, Science Translational Medicine (STM) analyzes the state of innovation in its June 29 issue.

STM states (without any authority) that “A powerful perception that innovation has stagnated persists in the biomedical research community.” STM asks, “Why have remarkable advances in basic biological science been so slow to be translated to improvements in clinical medicine?”

Unfortunately there is no identification of any “remarkable advances” that have been slow in being translated into clinical practice.

That’s not to say they don’t exist, merely the fact that from a hard-hitting science driven journal, it’s hard to hang your hat on mere assertions.

The three Commentaries on innovation by thought leaders in the June 29 issue offer varying perspectives, but like all opinion pieces it’s hard to judge competing views. STM in their editorial notes the only common thread they could detect among the Commentaries on innovation is that  “a new mindset must drive risk-benefit analysis.”

It is good to see a debate on innovation, but I think in the data driven world of science, I expected more from Science Translational Medicine and the American Association for the Advancement of Science (AAAS).

The first Commentary on Innovation published in the June 29 issue of STM is by Elazer Edelman, the Thomas D. and Virginia W. Cabot Professor of Health Sciences and Technology at MIT, and Martin Leon, Professor of Medicine at Columbia entitled “The Fiber of Modern Society.”

Why innovate? This is a good starting point for Edelman’s and Leon’s commentary. After all if innovation does not add value, then it’s a worthless exercise.  The authors, surprisingly for distinguished academics loose the reader in the first few paragraphs through their verbosity and lack of clarity:

Now grafted onto this engrained philosophy is a drop-off in the metrics of novelty and the perception that creation has stagnated—at least in biomedical science. As we are well into the 21st century, it behooves scientists and policy-makers not only to assess the accuracy of this impression but also to validate the long-accepted mantra.

The above causes me pain to read and attempt to process.  Does anyone really “behoove” anything in the 21st century?

The authors touch on competing views about what innovation is, but having raised the question of how to define it, fail to offer their opinion. Instead they move straight on by saying “irrespective of the definition.

Defining innovation is important – science is about preciseness. If you can’t define a theory how can you test it or measure it. While we may have different views of what innovation is, thought leaders on the topic should frame their perspective around some definition.

Is innovation really dead the authors go on to ask? They cite to the large number of publications in recent years that claim the death of innovation or express concern about it. However, while raising third-party concerns they also point out the progress that has been made in the reduction in mortality and morbidity over the past 40 years through advances in technology.

The authors again don’t answer the question they have asked on whether innovation is dead? Instead they move on to their next topic and suggest that “fear of risk stifles innovation” – spending cuts will lead to less creativity. The authors then launch into a diatribe on the pitfalls of a lower NIH budget.   Evidence of the demise of innovation is the decline in the number of registered patents or FDA applications for new molecular entities (NME).

What are the authors conclusions and recommendations?  They state:

“we must find ways to teach and support innovation without falling prey to conflicts of interest, without confusing innovation with greed-directed entrepreneurship.”

However, they don’t offer any specifics on how to do this, and what exactly is “greed-directed entrepreneurship” when it’s at home? Is it wrong to profit from innovation?

This Commentary by Edelman and Leon is not the deep insightful piece that Rodin’s Thinker suggests, instead it is a rambling piece that is disappointing in my opinion.

In future blog posts, I’ll be reviewing the other Commentaries on Innovation published by STM.

ResearchBlogging.orgEdelman, E., & Leon, M. (2011). The Fiber of Modern Society Science Translational Medicine, 3 (89), 89-89 DOI: 10.1126/scitranslmed.3002190

What is innovation? Like “strategy” and “leadership” it’s a term we frequently use, something we all seek in the biotech/pharma industry, yet it’s hard to define, even harder to develop or predict.

What is the future for innovative medicines in our industry’s pipeline? was the title of a session that I attended yesterday afternoon at BIO 2011, the annual meeting of the Biotechnology Industry Association (BIO) in Washington DC.

BIO 2011 Innovation Pipeline SessionModerated by John Mendlein, the panel contained some R&D heavy weights:

  • Tom Daniel, President of Research & Early Development, Celgene
  • Charles Homcy, Venture Partner, Third Rock Ventures
  • Moncef Slaoui, Chairman R&D, GlaxoSmithKline
  • Doug Williams, Executive VP, R&D, Biogen Idec

Several people in the audience live tweeted the key messages of the speakers, and I encourage you to review them, if interested.  The take homes that I took from this session were:

Innovation can be incremental or major breakthroughs

Many people think of innovation as a major breakthrough. Well worn clichés such as “ground breaking”, “game changing” come to mind.  In pharma, I’d cite imatinib (Glivec®/Gleevec®) in CML as an example.  In the consumer world, the Dyson vacuum cleaner jumps out to me.  Something completely redesigned and made better = innovation.

However, incremental change can also be innovation if it has an impact.  Take a new drug formulation that instead of daily dosing moves it to monthly doses and in the process improves patient compliance and adherence.  That’s incremental innovation.

“Incremental versus major breakthrough” reminds me of scientific research.  Most published papers are incremental, only rarely is there a major paradigm shift and landmark study.  Only a few PhD students undertake truly novel research, instead the majority pursue incremental avenues associated with their supervisor’s interests. An oversimplification perhaps but there’s some truth to it.

Understanding science enables Innovation

Companies should focus their energies on disease mechanisms where the basic science has reached an inflection point of knowledge i.e. there is enough information for us to apply. This is why the work of research organizations such as the National Institutes of Health (NIH) is so important. In an area where there is the disease knowledge emerging, you can then put together a team of people who understand the science and biology of the disease.  This does not guarantee innovation, but allows the identification of opportunities and in my view “enables innovation.”

Innovation will come from focus on molecular pathology of disease

Drug development is no longer focused on treating symptoms but on the underlying mechanism of a disease.  Medicine itself is moving in this direction with personalized medicine and drugs that target specific mutations of genes e.g crizotinib in lung cancer.  In a complex world of overlapping pathways (cancer and inflammation was the example cited), drug development innovation is going to come from understanding the molecular pathology of a disease. The terms “translational medicine” was not used in the session, but this is what comes to mind.  Understanding science is key to success.

What is the future for innovative medicines in our industry’s pipeline? The panelists didn’t actually answer this question directly, but my view is that it is promising.

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