Passive Restraint Solution to Prevent Congestive Heart Failure (CHF) following Myocardial Infarction

Drs. Ryan Krone & Karen Havenstrite discussed COR Innovations’ solution to preventing congestive heart failure (CHF), following myocardial infarction (i.e. heart attack) with a minimally-invasive, device-based technology, at www.bio2devicegroup.org .

Heart failure affects 5.8 million people in the U.S. alone and is responsible for nearly 1 million hospitalizations each year. The cost to healthcare industry in 2010 was a staggering $25B and is projected to triple to $75B by 2030. There is only 50% survival rate, 5 years after the diagnosis. Heart failure is a progressive disease. Myocardial infarction, commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die. This is most commonly due to occlusion or blockage of a coronary artery following the rupture of plaque clogging the walls of an artery. A vicious circle of ischemia, decreased cardiac output and reinfarction makes it largely incurable and progressive disease. First line of treatment regimen begins with prescription medications to help heart function and may include Beta Blockers, Diuretics, and ACE Inhibitors. But when the heart is greatly damaged and needs additional support, there are device based interventions including pacemakers and implantable Defibrillators. And finally there are surgical options that include heart valve repair, coronary artery bypass, implantable heart pump and finally heart transplant. Paracor was a company that offered passive restraint device to offload the weakened heart muscle. Though the device was less invasive compared to sternotomy, it was an invasive surgery, with added complications of severe immune response requiring the need for immunosuppressive medications with severe side effects and was therefore offered only to end stage patients.

COR Innovations has a novel passive restraint solution that encapsulates the heart in hydrogel which is highly biocompatible, eliminating the severe immune response. Further, it is significantly less invasive since the liquid hydrogel can be administered through the catheter and it can polymerize in-situ. This is FDA approved material, adheres to the heart, and is adjustable. However, there are challenges that the team is currently working to resolve. While the material offers great advantages, is perfectly suitable for the application, is biocompatible, and it disintegrates and leeches out in about a year, the bigger challenges are with respect to delivery. Once mixed, the material polymerizes in 30 seconds and the challenge is to ensure that the time is sufficient to encapsulate the heart. Also the ideal level of thickness versus the strength of the polymer for optimal restraint has to be found. The unique method of delivery makes it possible to deliver non-invasively but poses these challenges. Discussing the regulatory pathway, Havenstrite shared that they would follow the PMA pathway, given that this is a new material with a new indication. The topic generated great interest and was followed by Q&A.

Play Review – “Endgame and Play”

Play Review – Endgame and Play

Samuel Beckett, famous playwright and novelist, and disciple of James Joyce, had a reputation for writing about basic, primal human issues albeit from a perspective of wry humor. In 1969, Beckett was awarded the Nobel Prize for Literature and later he became most famous for his play “Waiting for Godot”. Currently, at A.C.T. in San Francisco www.act-sf.org , two of Beckett’s one-act plays, Endgame and Play, are played to packed audiences.

Play is performed first and is a short twenty-five minute long act with three characters, a man and two women, his wife and mistress, who are all individually trapped up to their necks, in three tall, ceramic urns. Each woman believes herself to be “the one” and despises the other. The characters speak together as well as in rapid succession and all of their harshness and fight occurs through words and facial expressions, because the characters are immobile and encased in urns. The spotlight is projected on their faces, when they speak. His choice of the topic of three-way love triangle reflects the most common everyday experience of any audience and his brilliant technique of having the characters trapped inside an urn reflects how each one is trapped in this love, hate, anger, sadness hell, with no end possible. Not only do they remember and regurgitate every petty, disgraceful detail but the entire play is repeated, thus further trivializing the petty details that mean so much to each of them, but mean so little in the larger life context. Moreover, initially the man tries to hold together, feeding what each woman expects to hear, but as the infidelity saga unravels and he is no more required to hold the façade, he becomes more detached and withdraws into his own memories of his rather empty, sad, lonely life. The dialog of each woman is similarly full of hate for the other woman at first and of deep sadness, as the clarity regarding the hopeless situation emerges. The irony of this oft repeated, most human of all stories, as it emerges from Beckett’s play, is that none of them are every truly “together”, as the man often repeats, “to think we were never together”. While the story is of and about love, in the end, love is not dominant in the life and in reminisces of any of the three characters, who are endlessly trapped in the drama, with all its pettiness.

One could imagine the difficulty of acting in this theatrical production. Play is brilliantly acted by Rene Augesen, Anthony Fusco, and Annie Purcell.

Endgame, was the longer one-act play, with a cast of four characters. The English title for the play originally written in French, was taken from the last part of the chess game, when there are very few pieces left and the end becomes obvious. Beckett apparently gave very detailed instructions and stage directions. Accordingly, it is staged in an empty room with two small windows placed rather high in the room, that Clov reaches by climbing a ladder, to look out from. Hamm, is an invalid and a tycoon who is seated in a ridiculous throne-like wheel chair, positioned in the center of the room, which is moved for brief periods when he insists on being moved by Clov, his clownish, suffering, slave of a caretaker.  Hamm seems to be dying in a world that appears to be nearing an end.  Hamm’s elderly mother and father live in two trashcans and once or twice they surface from inside the trashcans and in their gloomy conversations and helplessness, add their chorus to the main theme of the nearing end. At times, it is sadly funny, as one of the character says, “nothing is funny as unhappiness”. There isn’t much of a story that I got from the play and it certainly raises many profound questions, but provides few answers. What this play does poignantly portray is a scene of total helplessness of an invalid and other characters, environment of utter desolation, boredom, ruthlessness, sadness, no salvation from the mistakes made earlier, and in the end, life seems to boil down to lovelessness and nothingness. And yet, what it also portrayed is that regardless of the physical limits, both of one’s body and the environment, the human mind continues to remain free to choose to be harsh, to be slavish, to decide to break free (as Clov decides to leave Hamm).  The mind continues to roam free, imagine what might be happening outside the windows, to fantasize, to romanticize the youth, to tell stories, to seek listeners by cajoling and bribery, and on and on. Is it a story of total bleakness of life, life that is devoid of any meaning, and of inescapable death and helplessness or is it a saga of hope and imagination? You decide.

Giles Havergal and Barbara Oliver play the parts of Hamm’s elderly parents and Bill Irwin and Nick Gabriel brilliantly play the parts of Hamm and Clov, respectively.

If you are interested in light hearted entertainment, then skip this production of Beckett’s duel treat for the mind. But if you are interested in pondering over life, over love, over total lack of control and how people make meaning from it, over what life sometimes comes to mean, then this is the production that you may not want to skip.

Cancer Pathways, Evidence Based Medicine & What it Means for BioPharma Industry

 

Ellen Licking, writer and analyst for Real Endpoints, a start-up focused on providing objective information about product reimbursement, discussed “what cancer pathways mean for biopharma industry at www.bio2devicegroup.org.

Cost containment in healthcare has emerged as a significant issue and the payers are looking at big cost diseases like oncology to find more effective care options. The use of cancer care pathways is emerging as a strategy to focus on providing efficient care, while also containing costs. Results from existing “cancer pathway” pilots underway at national and regional insurers are becoming available in 2012 and are shedding light on the use of evidence-based medicine to improve outcomes and lower costs. In Europe, they discuss rationing of care. But in the US, it is a more complex issue, given the diversity of stake holders and the necessity for implementing politically appropriate language and behaviors.

Cancer pathways provide an evidence based-approach to care that is based on efficacy (how well the treatment works), toxicity (how toxic is the treatment), and cost. In the event that two drugs provide similar efficacy and toxicity, then the choice comes down to cost. Clear winners for reimbursement, in this approach, are efficacious drugs; for products that are as good, the choice is made based on price. First and foremost, this approach is designed to reduce the existing wide variation in care. Second, it aims to improve outcomes with focus on treatments that provide the greatest survival benefit and the lowest toxicity. Third, these care pathways would contain cost, based on scientific evidence of best care.

These pathways are not commandments in that payers are not mandating providers adopt a certain pathway. To get buy in from physicians, payers are considering waiving the right to prior authorization and programs that allow doctors to share in any financial savings. In one study, the data indicated 35% cost savings for on-pathways patients compared to those not on pathways, while showing no difference in survival outcomes. Real world cost savings, at least initially, are expected to be more modest in the 10-15% range. However, even these savings would greatly contain costs. Cancer pathways are small but growing quickly. Currently, there are an estimated 29 programs in place from a variety of payers. One concern has been that the pathway approach may change how oncologists are paid. Most oncologists are paid in relation to the amount and cost of drugs they prescribe. If payer savings translate into dramatic pay cut for oncologists then it would become challenging to get their buy in. Besides pathways, a few payers are experimenting with episode-of-care, which pays oncologists a single payment for treating patients during a specified treatment period.

What ARE the implications of these changes for THE biopharma industry? Given the dreaded oncology diseases, the treatment programs have traditionally been treated with kid gloves. But under this strategy, there will be clear winners and losers and treatments that are not efficacious will be dropped to make room for possible newer treatment options. While finding winning oncology drugs have always been challenging and will continue to be challenging, in the pathway driven world, it will also be more difficult to establish best in class drugs. Licking offered the recommended options for biopharma industry that include, maintaining focus on first in class drugs given the advantage to first to market, redefine meaning of best in class based on not just clinical efficiency but based on endpoints important to payers, in consideration of efficacy, to focus on price in addition to quality of life issues, and consider risk-sharing schemes that are tied to adherence medtrics or provide clear cost information such as Astrzeneca’s single payment scheme for Iressa. The talk generated a great deal of interest and discussion and was followed by Q&A. Ellen Licking can be contacted at ellen.licking@realendpoints.com; You can learn more about Real Endpoints at www.valueandinnovation.com .

 

Anant Agarwal on “Computers that Learn” – Keynote at TiEcon, 2012

Anant Agarwal, professor at MIT, Director of the Computer Science and AI Lab, and Founder of Tilera Corp. began his keynote address on Computers that Learn, at TiEcon, 2012 www.tiecon.org by stressing that computers suck up a lot of power and it is challenging to get power to them.  The current computing model is over 50 years old and is broken, said Agarwal.  The current model is procedural control model where computers keep running based on prescribed algorithms but do not learn along the way.  The problem will only get more magnified, as we get to possibly 1000 core processors by 2020.

How to fix this problem?  Agarwal shared his vision for Organic Computing that is based on lessons from biology.  The body regulates energy input and output based on the feedback loop.  For instance, when the body gets tired, it would work slower, run slower etc.  How does the body regulate the energy output to maximize efficiency?  Body gets feedback in various ways.  The new Organic Computing model can be built along the same lines to rethink computing, based on ODA or observe, decide, act loop.   First, such a system needs to be self-aware, where it can track the energy usage, in order to act on it.  Then it needs to be adaptive to respond to changing conditions, while maintaining performance towards prescribed goals.  This is not very far-fetched, considering that we already have machines that learn.  For instance, based on the pattern of the movies you request, Netflix will suggest other similar movies, because it learned about your taste and preference in movies, said Agarwal.  However, the challenge is that these computers will have to be intelligent learners in order for them to maintain performance, while learning and adapting to changing conditions, more like super athletes and less like common people.  New challenges of energy and complexity will require rethinking of 50 year old computing model and Organic Computing Model holds a lot of promise, said Agarwal.

Life Science focus at TiEcon, 2012

There were several panels that focused on Life Sciences and the mood was different at each of these sessions.  On day 1, a panel moderated by Mudit Jain focused on trends, challenges, and opportunities in this industry.  Almost all of the speakers, Dana Mead, Investment Partner, Kleiner Perkins Caufield & Byers, Renee Compton Ryan, Vice President, Venture Investments, Johnson & Johnson Development Corporation, Tom Fogarty, Founder, FogartyinstituteofInnovationand Katie Szyman, President, Medtronic Diabetes, painted a very bleak picture for this industry, in the years ahead.  The overarching tone was that the regulatory model is broken, regulatory hurdles are undefined and there is much higher unpredictability and risks in funding companies in the life sciences arena.  Until this model is fixed, the panel members stressed there would be fewer VCs willing to make sizeable investment in this space.  Various emerging markets seem to be more attractive and seem to be bigger growth sectors.

 

The panel on day 2, moderated by Halle Tecco, Co-Founder & CEO of RockHealth was more upbeat and discussed mobile health opportunities.  Panelist Alex De Winter, Partner at Life Sciences, Mohr Davidow shared that there was a lot of excitement regarding their portfolio companies mobile apps, driven by increased interest in wellness and staggering statistics around diabetes and obesity.  For instance, Aza Raskin’s company Massive Health is generating tremendous interest around its downloadable app that helps people eat healthier.  Technology is also often geography agnostic.  Mobile apps can originate anywhere and easily can be adapted for other geographies, said Winter.  In the opinion of Michael Nichols, Chief Privacy Officer at HealthTap, the landscape is also changing around the core theme of greater access to information and efficiency in healthcare.  Clive Smith founder of digital stethoscope, shared about the challenges posed by physicians in adopting new technologies on account of deeply entrenched old habits.  Jack Young, Lead Investment Manager at Qualcomm Life Fund, Qualcomm Ventures talked about the opportunities that exist in gamification with incentives to get people to adopt healthier lifestyle, which the insurance companies would find very attractive from reimbursement perspective.

Lessons about Entrepreneurship from Box.net CEO, Aaron Levie

 

Aaron Levie dropped out of college and started Box.net in 2005.  In fireside chat with Paul Singh, an early stage venture investor and advisor, Levie shared lessons from his entrepreneurship journey.  Levie’s first piece of advise? If you drop out of college and do not have lot of technical expertise then surround yourself with people who do.  When box.net was started in 2005, it was based on the firm belief that everything that was to be shared or stored would be on cloud and so they built the infrastructure, storage capability etc. and were signing up consumers as well as enterprise business.  But things were changing quickly on account of companies like Amazon and Google.  While consumer space was getting challenging, “looking at enterprise, we saw a huge opportunity”, said Levie.  The company quickly pivoted and shifted all R&D to focus on the enterprise market, in 2007.  Box enables companies to store all content online, so it can be easily accessed, managed, and shared from anywhere.  The new level of content management security that Box has pioneered is easy to use, with role-based access controls, and data encryption, and is focused on customized work flows.  Levie stressed that success is strongly about speed and agility.  In hindsight, if he were to change anything, he would make some faster decisions, perhaps even a faster hire or a faster fire.  Levie is incredibly bright, full of energy, full of great ideas and very witty.  It was a great keynote.

Opening Keynote at TiEcon 2012 by Vishal Sikka, Head of Technology and Innovation, SAP

Vishal Sikka shared some of the lessons he learned in professional journey.  One early realization for him was that bits are replacing atoms and value is being created by dissolving layers and structures and fueled by a cycle of connectedness, disintermediation, and ease of use.  User empowerment, communication, and education is enhanced with greater connectedness, said Sikka.  Earlier in his career, his boss told Sikka to focus on constantly intellectually renewing the company.  Sikka said he did not have the clarity in how one can intellectually renew a company of 50,000.  He has since realized that it has to be done on the basis of innovative products as well as the methodology used to bring innovation to life.  SAP focuses on renewing customer landscape without disruption, even when the innovation is clearly disruptive.  For instance SAP’s HANA platform enables query of multiple types of data sources with breakthrough transactional performance, at unthinkable speed, enabling many companies to not only run 10 times faster than traditional speed, but it enables some companies to run at 100X speed.  Sikka emphasized that it is important to not only focus on products but also on the process.  He stressed the importance of finding purpose in work and shared the ways in which SAP is enabling employees to find fun and greater meaningfulness in work.

 

Topical Capsaicin for Pain Management – Talk by Keith Bley

Dr. Keith Bley, CEO of Solimar Therapeutics and former SVP of Nonclinical R&D and a co-Founder of NeurogesX (www.neurogesx.com), talked about use of capsaicin, a pungent ingredient found in chili peppers, as treatment to relieve pain at www.bio2devicegroup.org.

 

There are many reasons why capsaicin has the potential to be effective pain reliever, said Bley.  Capsaicin, the principal ingredient in chili peppers, has antioxidant, antibacterial qualities and its pungency deters ambulatory herbivore animals from eating the fruits.  Birds however, do not respond to capsaicin and distribute seeds widely.  Although topical capsaicin therapy may cause an intense burning sensation for the first couple of minutes, it does not cause permanent tissue damage.  Capsaicin has unique receptors which selectively binds to heat activated sodium and calcium channels.  Bley shared the long history of interest and use of capsaicin for medicinal purposes.

 

More recently, capsaicin has been used in topical ointments, frequently to relieve the pain of peripheral neuropathy or pain associated with shingles.  Skin is the largest organ in the body and it is the primary sensing organ.  Nociceptors or specialized sensory nerve endings often become pathophysiologically hyperactive due to many insults that may cause reduction of skin intervention due to trauma, viruses, metabolic diseases, as well as drugs.  The idea is that if skin may contribute to pain then perhaps pain can be relieved by intervening at the level of the skin.  Existing capsaicin therapy required multiple applications and compliance was seen to be poor, on account of burning pain associated with the application.  NeurogesX combines the therapy into single application and increases the efficiency with higher concentration in its Qutenza 8% patch.  Interestingly, flooding the nerves with increased capsaicin also leads to defunctionalization where the nerves stop functioning temporarily and the pain soon subsides.

 

Bley shared some data from the clinical trial that indicated that compared to low-concentration patches, the Qutenza patch showed greater decline in reported pain and for the relief lasted a longer period, before another application was required.  While this data clearly favored Qutenza, of interest was also an absolutely strong and much more significant dip in reported pain, following both Qutenza and other low-concentration therapies, indicating a very strong placebo effect.  If in fact, immediate pain after the application was greater with Qutenza, due to higher concentration, compared to other patches, then it is very likely that the placebo effect will be stronger and last longer.  However, notwithstanding these concerns, given the subjective aspect of pain, Neurogesx was able to raise close to $150M and went IPO in 2007, got approval in Europe in 2008 and approval in US in 2009.  Bley’s presentation was followed by Q&A along with animated discussion about pain, pain relief and healthcare costs associated with pain relief therapies.  Keith Bley can be reached at kbeley@solimarthera.com .

Movie Review – “A Separation” (Iranian Film)

 

 

A Separation and possible divorce of Iranian couple Nader and Simin (married for 14 years) are at the heart of this movie. After months of trying and waiting, they got the visa to leave the country and migrate to the West and Simin wants to leave to give her daughter Termeh, a better future.  Nader however, is deeply occupied in carrying for his father who has Alzheimer’s disease and does not want to leave.  While this is a central theme around which the movie revolves, there are other dramas on the side that are equally engaging and give a deep insight into the cultural, class, and moral ethos of the Iranian society and yet other poignant situations show how similar human challenges are all over the world.  For instance, Razieh a deeply religious woman, retained by Nader to care for his father, calls the religious hotline to ask if it would not be a sin for her to clean Nader’s father who becomes incontinent.  On the other hand, the pull and sadness and turmoil that Termeh goes through being caught in the middle of her warring parents is identical to any teenager experiencing very similar feelings, upon encountering similar situation, almost anywhere in the world.

 

Razieh is pregnant, commutes long distance to take care of Nader’s father, and is soon overwhelmed caring for the old man with Alzheimer’s disease.  One day she ties his hand to the bed post and leaves for a visit to her doctor.  Nader returns home with his daughter and finds his father lying on the floor unconscious.  He is enraged and when Razieh returns, he accuses of her having stolen the money that also finds missing, and refuses to pay her, and asks her to leave.  She insists on clearing her name and insists on her payment and Nader shoves her out of the apartment. She falls and then hurries out.  Later, she looses her child and there is court drama where Nadar is accused of killing the unborn child and Nader accuses Razieh of neglecting his father and Razieh’s hot headed husband makes threats against Nadar and his family.  Upon insistence of his wife, Nader offers to pay blood money and drop the feud, at which point Razieh refuses to take the money saying that just the previous day before Nader shoved her out of the building, his father had wandered off from home and as she went looking for him and as she ran to keep him from being run over by cars, a car had bumped into her.  She feared that her miscarriage might be the result of her being hit by the car and if she accepted the money than Almighty’ wrath would fall upon her and her family.  This enraged her husband who owes money to creditors and will likely be jailed.  Nader and Simin leave them and then go to proceed with their divorce.  The movie ends with the judge drawing the separation papers and then asking Termeh to choose the parent she would like to live with.

 

This was an intense movie with much food for thought.  Almost anyone can relate to how much the teenager is torn between her parents.  It seems while she might prefer to live with her mother, she feels they would never get together again, unless she continues to live with her father.  We can also relate to how Nader is sandwiched between caring for his father and caring for his daughter and taking care of the home, after his wife leaves.  Razieh and her husband, on the other hand, are struggling with poverty and perhaps even wrongly accused of theft and of looking to make free money out of their tragedy.  I loved the movie.  It is beautifully made, avoids exaggerations, and in the end, one feels nothing but compassion for each and every character caught in the middle of life’s many challenges and constraints.  The movie won 84^th Academy Award for Best Foreign Language Film in 2012, becoming the first Iranian film to win the award and received Best Film, Best Actress, and Best Actor award at the 61^st Berlin International Film Festival and also won Golden Bear and 69^th Golden Globe Awards for the Best Foreign Language Film.

Poem – Mother’s million things for children

Once you were young and beautiful
Perhaps you turned eyes, you were so cool
Perhaps you had dreams and desires
To learn, travel, explore new shores

Instead, bound by social norms
You bore daughters and sons
Sometimes we did not care, did not understand
Sometimes we rebelled and sassed

But you never failed to rise
To tend to each of our cries
To a life not of your choosing, but your calling
You gave all, abundantly, loving and smiling

Keeping warm our food each day
When we came from school, August to May
How did you do it? Find love in your heart
Sometimes when life was far from perfect

You found a way to look past life’s sorrow
Your eyes on our dreams, as you sat by the window
At times you sat with us, yawning and sleepy eyed
Well past midnight, as we sat and studied

You never strayed from our bedside, when we got ill
Afraid to move, lest it awaken us, you sat still
Holding our little fingers, as we put entire trust in your palm
You took us for little treats, your presence soothing like a balm

Cooked, scrubbed, swept, even as you did your million chores,
As we slept late into the morn, dreams dancing on our eyelashes.
Now you are old and feeble and perhaps have forgotten your sacrifices
A life devoted solely to your children, no other desires or vices

A million things you did for each of us, amidst your busy day
Have we too forgotten? A debt of deep gratitude, we can’t ever repay?