Biotech Strategy Blog

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

Posts tagged ‘Science Translational Medicine’

Contrary to popular opinion, innovation is not dead in the biomedical industry, as evidenced by news of a novel drug-delivery system published as a Rapid Publication in Science Translational Medicine (STM) on February 16, 2012.

The paper from Robert Farra of MicroCHIPS, Inc. and research collaborators, describes a first-in-human testing of a wirelessly controlled drug delivery microchip.

Farra et al., report the results of a clinical trial with 8 women in whom microchips were implanted for 103 days. The data showed that the pharmacokinetic profile of microgram-quantities of the anti-osteoporosis drug, teriparatide (FORSTEO), delivered by the microchip was similar to subcutaneous injections.  However, the device did fail in one of the 8 women, so data is only reported for 7 patients, a very small patient sample.

Picture Credit: MicroCHIPS, Inc.

The drug delivery device is an array of 600-nL micro reservoirs in which the drug is stored, that is associated with a 13.0 mm x 5.4mm x 0.5mm silicon chip.

The microchip was implanted beneath the skin (subcutaneously) in the abdomen by creating a 2.5cm incision, performed during an outpatient visit.

This paper is also interesting for its use of telemedicine. A remote operator was able to establish a wireless link and send instructions directly to the implant on dosing schedule as well as receive information back on operation of the chip.

John T. Watson, Professor of Bioengineering at the University of California San Diego  commented in the accompanying editorial that:

“The microchip represents more than 10 years of engineering design and development efforts to arrive at a programmable, implantable device for subcutaneous release of a therapeutic agent in discrete doses.”

Multiple engineering design advances were made along the way.

He also noted the results from the quality-of-life surveys administered during the trial; the majority of women stating they often forgot they had the device implanted and would readily consent to a fresh implant if needed.

Innovations in drug delivery offer hope of an improved quality of life to patients with chronic disease who require daily injections.  In 2010, there were approximately 50,000 teriparatide users, not an insignificant market opportunity.  People with diabetes who require daily injection of insulin is another potential market that springs to mind.

The first-in-human results reported in Science Translational Medicine show promise and the potential of a novel implanted wireless drug delivery system.

However, many questions remain unanswered by this research including the reliability & durability of the microchip device, given that it failed in 1 out of 8 women implanted.

Further work on validating the technology, and confirming its safety, reliability and efficacy in a larger sample size will be needed before it can obtain regulatory approval.

References

ResearchBlogging.orgFarra, R., Sheppard, N., McCabe, L., Neer, R., Anderson, J., Santini, J., Cima, M., & Langer, R. (2012). First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip Science Translational Medicine DOI: 10.1126/scitranslmed.3003276

Watson, J. (2012). Re-Engineering Device Translation Timelines Science Translational Medicine DOI: 10.1126/scitranslmed.3003687

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

Nanotechnology is set to have a major impact on drug development and new products for the diagnosis and treatment of cancer.  Research from UCSF and Northwestern University published earlier this year in “Science Translational Medicine” shows this potential.

Edward Chow and colleagues describe how binding the cancer chemotherapy doxorubicin (DOX) to carbon nanoparticles 2-8nm in diameter in the form of a diamond, “nanodiamond” (ND), improved drug efficacy and overcame drug resistance.  Although this pre-clinical animal research has not yet been confirmed in humans, it raises the possibility of more efficient chemotherapies and the hope of increased survival rates as a result.

The conclusion from this research is that nanodiamonds may be a viable drug delivery platform for small molecules, proteins and nucleic acids. This technology could have an application in wide range of diseases.

Why is nanoparticle-mediated drug delivery more effective? The paper suggests one reason is that the nanodiamond-doxorubicin complex (NDX) allows for a more gradual release of DOX, allowing for increased tumor retention and increased circulation time.

It’s important to note that the NDX complex does not specifically target the drug efflux pumps, such as MDR1 and ABCG2 transporter proteins, responsible for chemoresistance. Instead the NDX complex appears to overcome drug resistance passively by the way DOX is released from the nanodiamond.

This research shows that taking old drugs and combining them with new drug delivery technology may offer therapeutic benefits.  The authors conclude that this research, “serves as a promising foundation for continued NDX development and potential clinical application.”

If successful in humans, it will translate into new product development and market opportunities for emerging biotechnology and biopharmaceutical companies.

 

ResearchBlogging.orgChow, E., Zhang, X., Chen, M., Lam, R., Robinson, E., Huang, H., Schaffer, D., Osawa, E., Goga, A., & Ho, D. (2011). Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment Science Translational Medicine, 3 (73), 73-73 DOI: 10.1126/scitranslmed.3001713

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