Thursday, October 27, 2011

Regenerative Medicine and Cell Therapy Briefing: The Road to Commercialization

The following blog was originally posted on Prize4Life's ALS Forum. For more articles on the latest research and drug development news, along with a wide variety of ALS research tools and resources, visit

Amidst the buzz of partnering activity throughout the three day BioPharm America 2011 meeting held in Boston, MA from September 7-9, 2011, there were ample opportunities to hear industry leaders' perspectives on industry trends through workshops and panel discussions. Of particular interest was a session focused on stem cells in regenerative medicine and featured here, given the powerful allure of stem cells to captivate ALS researchers, drug developers, and patients alike. With the generation of ALS patient-derived iPS cell lines and the ground-breaking safety trial of Neuralstem's stem cell therapy in ALS patients, there are high expectations for stem cells to revolutionize ALS drug discovery and therapeutics. Let's hear what industry leaders had to say ...

The session opened with a panel moderated by Brock Reeve, Executive Director of the Harvard Stem Cell Institute. In his introductory comments, Reeve reminded the audience that the first iPS publication came out just five years ago and since then the technology has become almost commonplace in labs across the world. Moreover, the technology has already been improved upon: a subsequent technique was developed to directly induce differentiated fibroblasts into a motor neuron identity, skipping the reprogramming step to the undifferentiated state. These so called induced motor neurons (or iMN) could potentially make it even easier and faster to generate patient specific models of motor neuron disease. [See also related news on recent advances to purify and differentiate stem cells as well as remaining potential pitfalls.]

The "big opportunity" that lay in stem cells was clearly appreciated by the pharma and biotech panel experts who acknowledged the growing trend to incorporate adult, embryonic or induced pluripotent stem cell technologies into a variety of efforts, ranging from drug discovery to development of cell-based therapies. The exciting ferment in the stem cell space has also added to industry's growing interest in and enthusiasm for fostering academic collaborations. While innovation in the stem cell space can come from anywhere, Gary Neil, Corporate VP at J&J, expects most to come from the academic sector.

Both panelists and audience members commented on the more frequent appearances of pharma representative of the likes of Pfizer, J&J, and GSK turning up at regenerative medicine conferences and partnering meetings such as this one as illustrative of pharma's growing interest in regenerative medicine. One explicit example of this interest, Shire's recent acquisition of AdvBioHealing, was taken as a signal that the specialty pharma's intends to build a regenerative medicine franchise around its newly acquired iPS technology.

Reeve asked panelist to offer their perspectives on potential breakthroughs within the proximate five-year horizon for regenerative medicine. Near term success was expected for macular degeneration and other eye diseases as well as for diabetes. Simple models with easy to measure clinical endpoints were perceived as more likely to succeed, whereas diseases with more complex biology (i.e.: stroke and ALS) were perceived as more difficult.

The second panel moderated by John McNeish, Founder of Boston Stem Cell and ex-Pfizer Executive Director of Regenerative Medicine, explored the use of stem cells for drug discovery and translation in greater depth. iPS cells in particular hold great excitement for use in disease modeling, target validation, and drug and biomarker discovery programs. iPS cells also offer a unique opportunity to identify which patients are more likely to respond to a drug by first testing the drug on the patient's own stem cells. In contrast to the relatively young iPS field, panelists noted that the more mature areas of adult and embryonic stem cell biology have yielded several cellular therapies that have moved steadily ahead into a clinical setting, including Advanced Cell Technology's hESC-based Retinal Pigment Epithelial (RPE) therapy for degenerative retinal diseases, Geron's hESC-derived oligodendrocyte progenitor cell therapy for spinal cord injury, Neuralstem's neural stem cell therapy for ALS and major depression, and over 37 ongoing clinical trials using adult stem cell therapeutics.

How close are we to remediating disease in a dish? Very close, according to Leonard Zon, stem cell researcher at HHMI/Children's Hospital Boston and co-founder of Fate Therapeutics, who projects that in three to five years researchers will be able to successfully treat a disease pathology exhibited by the affected cell type derived from patient iPS cells. This is an area of intense investigation, as many groups are actively working to establish disease models in a dish from patient-derived iPS cells and to develop functional assays to enable drug screening, including those studying ALS at The New York Stem Cell Foundation, the California Institute for Regenerative Medicine and elsewhere.

For ALS, progress has been slowed by an unanticipated finding. Unlike motor neurons derived from ALS mouse ESCs, which exhibit a characteristic disease pathology, motor neurons generated from both familial and sporadic ALS patient iPS cell lines lack an obvious disease phenotype even after extended periods in culture. The apparently healthy nature of these cells may bode well for transplantation back into the patient for use as a cellular therapy. However, the difficulty in detecting a disease phenotype necessitates the development of sensitive assays to identify a disease signature, a necessary step before these cells can be used to screen drugs.

While progress is being made on several fronts to advance stem cell-based drug discovery and therapies, the field continues to wrestle with the hype surrounding stem cells - a double edged sword for the field. While a certain amount of hype attracts investment money, it also preys on the vulnerabilities of patient communities, desperate for treatment. As ACT's Business Development Director Matthew Vincent noted, regenerative medicine's snake oil practitioners will hamper legitimate scientific efforts and slow the entire field. He cautioned against getting caught up in the hype and hubris over the revolutionary nature of stem cells when it comes to managing the associated risks, which range from regulatory to manufacturing to reimbursement. Goeff MacKay, President and CEO of Organogenesis, further emphasized the importance of assessing reimbursement very early in the process, calling it an early go/no-go decision point.

To watch the videos of the regenerative medicine panels presented here, click the links: panel 1 and panel 2. Additional meeting coverage discussing pharma trends can be found here: The future of drug development, Angus Russell: Pharma must change to compete in new world market and Creativity, productivity and the future of pharma.

- Sheila Menzies, PhD, Scientific Program Officer at Prize4Life

Tuesday, October 25, 2011

Dr. Ed Kaye on ALS and Incentive Prizes: The Extended Interview

As part of our continuing series featuring interviews with some of the leading players in the field of ALS research, drug development, and treatment, Prize4Life spoke with Dr. Ed Kaye, currently the Chief Medical Officer at AVI BioPharma and the former Group Vice President and Therapeutic Head for Lysosomal Storage Disorders and Neurodegenerative Diseases at Genzyme Corporation. Dr. Kaye serves on Prize4Life's Scientific Advisory Board. In this video, he shares his thoughts on the recent $1M ALS Biomarker Prize award, the importance of private funding to complement public funding of ALS research, and the potential of the incentive prize model in biomedical research.

You can watch all of the extended interviews by subscribing to our YouTube channel here. You can also view the original video these interviews were collected for, 'Driving Breakthroughs in ALS Research: Prize4Life and the $1M ALS Biomarker Prize,' below.

Friday, October 14, 2011

Dr. Robert Horvitz on ALS Research: The Extended Interview

Earlier this year, Prize4Life interviewed some of the top minds in the ALS research, clinical, and industry communities asking for their thoughts on ALS, the drug development landscape, and the potential of the incentive prize model in spurring biomedical innovation. These interviews were compiled into a short video that was screened at a gala in New York City celebrating the awarding of the $1M ALS Biomarker Prize to Dr. Seward Rutkove.

We are sharing the extended versions of these interviews on our website. The first video featured Dr. Vicki Sato, a professor at Harvard Business School and former president of Vertex Pharmaceuticals. You can view that video here.

The following is an interview with Dr. Robert Horvitz, a Professor of Biology at the Massachusetts Institute of Technology, an investigator with the Howard Hughes Medical Institute, and winner of the 2002 Nobel Prize in Physiology for discovering and characterizing the genes controlling cell death in the nematode worm Caenorhabditis elegans. Dr. Horvitz discusses his personal connection with ALS, the need for increased funding in the field, and how his work advances ALS research.

You can also view the original video, 'Driving Breakthroughs in ALS Research: Prize4Life and the $1M ALS Biomarker Prize,' below.

Tuesday, October 11, 2011

5K4Life Is Fast Approaching!

The Third Annual 5K4Life, benefiting Prize4Life, is almost upon us!

Our founder and CEO, Avi Kremer, will be in attendance for the race this year. Avi was diagnosed with ALS in 2006 and launched Prize4Life to rapidly accelerate the discovery of a cure for the disease.

When: November 6th
8:00 - 10:45 AM Race Registration and Race Packet Pick-Up
11:00 AM Race Start
Where: Kendall Square / 15 Cambridge Center

Members of Team Ashley helped make last year's 5K4Life a tremendous success...

ALS is a devastating neurodegenerative disease that afflicts more than 600,000 people around the world, robbing them of the ability to move, speak, and ultimately to breathe. Most patients will die within 2 to 5 years.

But you can be a part of the cure! Support Prize4Life's efforts to drive breakthroughs in research at the 5K4Life!

Here's how you can help:

1. Register today for the 5K at
2. Volunteer for the race by emailing
3. Donate to Prize4Life here
4. Fundraise for the 5K4Life to help bring us closer to a world free of ALS

Fundraising for Prize4Life is a way to honor someone you know living with ALS, to remember someone who has passed away from the disease, or to deliver hope to the thousands of ALS patients and their families battling it. Join Prize4Life's efforts, and the next ALS breakthrough could be yours...

Create your own fundraising page here.

Thank you for your support! Please share word of the 5K4Life with your friends and networks, and RSVP for the race on Facebook.

Thursday, September 8, 2011

"Trapped" Can Now Be Viewed Online!

In April of 2009, a group of filmmakers came together to create "Trapped," a short film meant to raise awareness of ALS and marshal support for efforts to discover a cure. Director/Producer James Takata, Writers/Producers Zach Lewis and Jim Mahoney, and Producer Jhennifer Webberley worked with Amy Yamner Jenkins, the Chair of Prize4Life's Board of Directors, on the project. The film tells the story of Stephen, a talented young composer and pianist who discovers he has ALS after an eerie progression of symptoms. And though he begins to lose his ability to physically write music and play the piano, his spirit and genius cannot be taken by the disease. As Director Takata describes, though is body is deteriorating, "his ability is still there."

"Trapped" has been shown at numerous festivals, including the California Independent Film Festival, Methodfest, and the Neuro Film Festival sponsored by the American Academy of Neurology Foundation. The film won a bronze medal at the New York-based Telly Awards.

In 2009, Prize4Life had the opportunity to sit down with some of the creators of the film. You can read a transcript of that interview on our blog here.

For more information on the film's cast and crew, visit the IMDB profile page here.

Monday, August 22, 2011

Mice in Space: The Effects of Low Gravity on Muscle and Bone Degeneration

On July 21, 2011, the American space shuttle program came to an official end when shuttle Atlantis rolled to a stop at NASA’s Kennedy Space Center on Merritt Island in Florida. For 30 years, the shuttle program ferried astronauts into Earth’s orbit to launch, repair, and recover satellites, construct the International Space station, and conduct countless experiments and invaluable scientific research.

One such experiment, undertaken during the final shuttle mission, studied the loss of bone and muscle mass in a micro-gravity environment as well as a therapy that might be able to arrest that degeneration. Mary Bouxsein, PhD, a scientist in Beth Israel Deaconess Medical Center’s (BIDMC) department of Advanced Orthopedic Studies and Assistant Professor of Orthopedic Surgery at Harvard Medical School, served as the co-principal investigator of the study, leading a team of researchers from BIDMC, Amgen, BioServe Space Technologies, and the University of North Carolina. The study was funded by NASA’s Ames Research Center.

The research will not only yield insights into how astronauts can address a fundamental problem of long space flights, it could also lead to a greater understanding and potential prevention of bone loss for aging or diseased individuals here on Earth.

“Mechanical loading is required to maintain musculoskeletal health,” explains Dr. Bouxsein. “On earth, our bones experience mechanical forces from being pushed and pulled by muscles that work against gravity to keep us upright and moving around, as well as from the impact of our body weight against the ground. These forces are much lower in micro-gravity environments and, as a result, the rate of bone loss among astronauts is about 10 times greater than that seen in postmenopausal women. So, while this research is designed to better understand and prevent skeletal fragility among astronauts, it may also tell us a great deal about the future potential of this novel therapy to improve bone strength here on earth, in both older persons and in individuals with reduced physical activity due to various clinical conditions, such as stroke, spinal cord injury or cerebral palsy.”

You can watch Dr. Bouxsein explain her team’s work leading up to the shuttle launch in the video below.

Thirty mice (affectionately dubbed ‘mousetronauts’) were launched into space as a part of mission STS-135, the final shuttle flight. Dr. Bouxsein’s rather enthusiastic blog details the mission from soup to nuts (or launch to post-touchdown beach party after all of the equipment, supplies, and specimens had been collected at the Kennedy Space Center). You can read her blog here.

One of Dr. Bouxsein’s collaborators was Dr. Seward Rutkove, also of Beth Israel Deaconess Medical Center. Dr. Rutkove is the Chief of the Division of Neuromuscular Diseases at BIDMC as well as the recipient of Prize4Life’s $1M ALS Biomarker Prize.

Dr. Rutkove’s lab will be conducting studies over the next six months on the two specimens they received from the experiment in order to learn more about the progression of muscle atrophy that accompanies disuse. Rutkove is the developer of electrical impedance myography (the work for which he won our million-dollar prize), a process which compares the flow of an electrical current through healthy muscle and muscle that has degenerated as ALS progresses. You can read more about EIM technology in an earlier blog post here.

There is currently no reliable diagnostic test for ALS. However, by making a distinction between the muscle degeneration that occurs due to illness or lack of use (accentuated in this experiment by the micro-gravity of a low Earth orbit) and atrophy that stems from a neurogenic disorder, electrodiagnostic tests might be able to tell scientists more about the nature of ALS in a given patient sooner which could improve the impact of potential therapies.

Friday, August 19, 2011

Out With The Old And In with the … Old: The Drug Repositioning Conference

"One of the things you learn from years of dealing with drug people, is that you can turn your back on a person, but never turn your back on a drug."

- Raoul Duke, Fear and Loathing in Las Vegas

"In the field of observation, chance favors only the prepared mind."

- Louis Pasteur

The above quotes allude to the growing realization that new opportunities exist for many "old" drugs, but sophisticated knowledge management platforms will be needed to properly identify these drug repositioning opportunities.

Amid the "fear and loathing" accompanying the numerous reports of the drug development pipeline drying-up, the biopharmaceutical industry is warmly embracing the drug repositioning model as an efficient and expedited mechanism to fuel their clinical development programs with "old" drugs that have newly appreciated indications. At the recent Drug Repositioning Conference held in San Francisco, CA on July 13-14, 2011, industry experts convened to share their insights from their own drug repositioning experiences, to discuss the impact drug repositioning has had on the drug development landscape, and to assess new directions for the field.

The concept of drug repositioning (or repurposing) is not new. In the past, serendipitous observations played a principle role in identifying novel uses for approved drugs already on the market for other indications, noted Pankaj Agarwal, Director of Computational Biology, Molecular Discovery & Development at GlaxoSmithKline. Aspirin serves as a classic example.

What is new however is that biopharmas, including Merck Serono, AstraZeneca and GSK, all of whom were represented at this conference, are now placing a premium on leveraging their prior research and development (R&D) investments to rescue stalled clinical-stage compounds by re-investigating their efficacy for treating alternative new indications.

Given the high attrition rate of experimental drugs, drug repositioning offers a "solution for speedy re-introduction of compounds back into the pipeline," commented Natalia Novac, Associate Manager, R&D Knowledge Management Operational Excellence at Merck Serono. While Novac commented that Serono's original repurposing business model had focused on Phase 3 clinical compounds, they now realize that they need to start earlier, after a drug passes Phase I safety and toxicity testing, to plan for secondary indications. Others in the audience advocated preparing even earlier, at the preclinical stage in the product lifecycle, a practice adopted at Pfizer, to identify potential alternative indications that could be used either as a back-up, if efficacy testing for the primary indication fails, or as a repositioning strategy.

Some in the audience challenged the notion that only drugs that have passed Phase I harbor future value for repurposed use, indicating that a drug that failed its initial Phase I study when delivered at a high dose could be safely delivered at a much lower dose that fell within the therapeutic window for the treatment of an alternative indication. Taken together, these divergent criteria argue the utility of broadening eligibility to include all clinical compounds (and perhaps even preclinical compounds) under consideration for repositioning.

Knowledge Management: Pillar of the Drug Repurposing Approach

Nowadays, biopharma is not leaving these hidden, yet potentially golden, repositioning opportunities up to chance alone. There is a concerted effort within biopharma to capture and organize the vast amounts of existing public and proprietary data into rich knowledge networks of biological pathways and disease targets.

Merck Serono, AstraZeneca, and GSK are all heavily investing in various Knowledge Management platforms. Speakers mentioned a host of existing automated technology platforms that review texts (i.e.: publications, abstracts, clinical case reports, etc.), extract entities (i.e.: proteins X and Y) and build relationships between entities (i.e.: protein X activates protein Y) to create biological knowledge networks. These networks could be overlaid onto disease specific network maps to facilitate identification of key, possibly novel, disease targets. This type of approach could also be used to identify the relevant indication(s) based on their drug's established mechanism of action.

In addition to fully automated platforms, organizations such as Thomas Reuters offer MetaMiner Partnerships to "bring the highly specialized expertise in manual curation and disease map development to create new pathways quickly" for its clients. In a collaborative move, Reuters launched a new consortium in July 2011 to map the bioprocesses for all FDA drugs approved in the last three years.

Spotlight on AstraZeneca's High-Investment Foray into Drug Repurposing

AstraZeneca's aptly named New Opportunities group has been tasked with finding new opportunities for existing compounds in areas that the company is currently not working in. Regenerative medicine is one such new area, remarked Nick Brown, Associate Director of Informatics for AstraZeneca's New Opportunities group. Orphan diseases were also considered attractive gateway indications, suggesting that ALS could be within AstraZeneca's sights if the right opportunity were to be identified.

AstraZeneca is going further than most when building their Knowledge Management Platforms. As Brown explained, his group is in the process of bringing together over 2000 proprietary internal databases from across AstraZeneca's global reach. He admittedly faces a huge standardization challenge, but makes the point that these disparate databases contain tons of valuable proprietary information about their own drugs that remain relatively inaccessible. Brown strongly believes that re-capturing this propriety information "hidden away" will reveal novel and lucrative repurposing opportunities for AstraZeneca. Brown has also developed a rich Asset Repositioning Matrix that has already led to the identification of new disease targets and indications, as well as, potential collaborators and key opinion leaders.

The 20-member group functions as a virtual R&D with a budget comparable to one of AstraZeneca's therapeutic areas, underscoring their confidence in and commitment to the repurposing strategy. Formation and funding of this group also emphasizes AstraZeneca's belief, also expressed frequently by other conference attendees, that factoring human data into the knowledge maps is "huge". Given the size of AstraZeneca's investment and commitment it was interesting that the primary focus to date for this group had been on late stage Phase II or III compounds in clinical development, suggesting that a considerable amount of Phase I and pre-clinical information still remained untapped.

The value proposition behind the drug repositioning approach is obvious: generate new revenue streams by leveraging prior capital- and resource-intensive investments and in so doing offer patients better treatments. While the opportunities are vast, there are several important limitations, including issues of commercialization, patentability, freedom of use, and the regulatory path to approval, to name just a few. Not to fear - speakers including commercialization expert David Cavalla, regulatory expert Ken Phelps, and patent attorney Kevin McLaren, discussed a slew of strategies to work through these vital issues. Further discussion of these issues can be found here and here.

So given the buzz generated at this conference, my question is: can ALS drug development benefit from a drug repositioning approach?

One way I thought about this was in terms of speed. The critical need for expedited drug development for ALS is underscored by the aggressive and merciless progression of disease resulting in death typically within three years after diagnosis. Clinical development of a repurposed drug could significantly shorten the traditional drug development timeline and bring an efficacious drug to patients faster and, in so doing, offer access to more ALS patients.

Ok, so yes, repositioning saves time, but is it relevant to ALS? As noted by speaker Chris Lipinski, Scientific Advisor at Melior Discovery, 30% of clinical compounds have new uses and (strikingly) 90% of these new uses are on-target. These findings indicate that rather than finding new molecular targets for old drugs, we are discovering the relevance of these druggable targets in new indications, implying that there are major gaps and flaws in our fundamental understanding of disease biology.

Final thought: As our understanding of ALS biology deepens and disease targets are further validated, a drug repurposing approach could be a valuable complement to traditional ALS drug discovery efforts.

So who's with me?

- Sheila Menzies, Scientific Program Officer at Prize4Life

This blog post was originally published on the ALS Forum at

Wednesday, August 10, 2011

Dr. Vicki Sato on Prize4Life: The Extended Interview

In June of 2011, Prize4Life formally celebrated the awarding of the $1M ALS Biomarker Prize to Dr. Seward Rutkove for his development of eletrical impedance myography (EIM), a tool that has the potential to radically accelerate the development of drugs for ALS. To mark that occasion, Prize4Life interviewed some of the top minds in the ALS research, clinical, and industry communities asking for their thoughts on ALS, the drug development landscape, and the potential of the incentive prize model in spurring biomedical innovation. These interviews were compiled into a short video screened at our award gala.

Over the course of this summer, Prize4Life will be releasing extended versions of those interviews on our website and social media channels. The first is an interview with Dr. Vicki Sato, a Professor of Management Practice at Harvard Business School, a Professor of the Practice in the Department of Molecular and Cell Biology at Harvard University, a business advisor to Atlas Ventures, the former President of Vertex Pharmaceuticals, and a current member of Prize4Life's Board of Directors.

You can also view the original video, 'Driving Breakthroughs in ALS Research: Prize4Life and the $1M ALS Biomarker Prize,' below.

Stay tuned for additional interviews to be released at, or follow along on our Facebook page or our YouTube channel.

Friday, June 10, 2011

Biogen Idec/Knopp Biosciences Dexpramipexole Trial

In early April, Knopp Biosciences and Biogen Idec announced the enrollment of the first patient into a Phase III clinical trial of the experimental drug dexpramipexole, a novel treatment to extend the lives of individuals with ALS. It is an exciting development for the field, and we wanted to highlight some of the details and history of the drug for the blog.

The trial will enroll 804 patients who will be followed for 12-18 months. Half of this group will receive two doses per day of a 150mg oral tablet of the drug; the other half will receive a similarly dosed placebo.

In order to participate in the trial, patients must:

  • Be 18 to 80 years old.
  • Have a diagnosis of familial or sporadic ALS.
  • Have experienced symptom onset within 24 months prior to beginning the trial.
  • Meet World Federation of Neurology El Escorial criteria for a “possible,” “laboratory-supported probable,” “probable” or “definite” ALS diagnosis.
  • Have lung function of 65 percent or more at screening, measured by a test called the upright slow vital capacity (SVC).
  • Be able to swallow tablets at the time of study entry.

Participants must not:

  • Have any other medically significant illness.
  • Have any clinically significant abnormal laboratory values.
  • Be pregnant or breastfeeding.
  • Have prior exposure to dexpramipexole.
  • Be currently taking pramipexole or other dopamine agonists.

The trial will be enrolling patients at 83 locations in 28 states and 10 countries (Australia, Canada, and several European countries). For more detailed enrollment information as well a list of study locations, visit the listing for the Phase III dexpramipexole trial at It should be noted that most sites have yet to start recruiting as of the publication of this post. Contact information for individual sites can be found at, and the Medical Director of the study at Biogen can be reached at

A brief history of dexpramipexole:

Early 2000’s – Dexpramipexole is first identified as a potential ALS therapy by Dr. James Bennett of the University of Virginia and first preliminary academic clinical studies are conducted using Dex to treat ALS patients.

2007 – Knopp Biosciences completes a formal Phase I trial of dexpramipexole that demonstrates the drug is safe and well-tolerated among healthy volunteers.

2009 – Results from a Phase II study of the drug again demonstrate safety and show a ‘dose-dependent trend in slowing the rate of disease progression’ in the first part of the study and a ‘trend toward a survival benefit’ among the highest-dosed patients in the second part of the study. Drug receives ‘fast-track’ designation from the US FDA.

2010 – Knopp Biosciences and Biogen Idec enter into an exclusive, worldwide license agreement to develop and commercialize dexpramipexole.

2011 – Knopp Biosciences and Biogen Idec enroll first patient in Phase III clinical trial of dexpramipexole.

So what is the expected benefit of dexpramipexole (colloquially known as dex)?

According to Michael Bozik, a neurologist and the President and CEO of Knopp Biosciences, “If we confirm in larger studies what we saw in earlier studies, we believe it has the promise to extend life [up to six months or more].”

Riluzole, the only currently available drug for ALS, extends life by about 2-3 months. Patients who are currently taking Riluzole are not disqualified from participating in the Phase III trial, though they must either have been taking a stable dose of the drug for at least 60 days or have discontinued the drug for at least 30 days.

Though the launch of this trial is an encouraging development, there are still several hurdles that must be cleared. The Phase III trial will enroll eight times the number of patients as previous Dex trials and will need to exceed the relatively ‘modest’ effect demonstrated in the Phase II trial. Additionally, the mechanism behind the drug is not well understood. According to Dr. Bozik, Knopp is still researching the underlying function of the drug in collaboration with Yale University. Finally, even if the trial demonstrates efficacy, the earliest an application for FDA approval could be submitted is 2013—assuming the study is completed on time (estimated end date of February 2013) and the FDA does not require a second round of Phase III trials.

Nevertheless, dexpramipexole provides cause for hope for the thousands of patients and families battling this disease. We will continue to closely follow and report on any developments related to this drug.

Thursday, March 24, 2011

Prizes 101: An Introduction to Prizes for Global Health Innovation on World TB Day

A guest blog post from our colleagues at Results for Development:

World TB Day, which falls on March 24 every year, marks Dr. Robert Koch's discovery of Mycobacteriumtuberculosis, the bacteria that cause tuberculosis (TB). Dr. Koch's discovery was a remarkable step forward in diagnosing, treating and fighting the TB epidemic, which takes over two million lives every year around the world. Despite the global interest in curbing the TB epidemic, the technology to diagnose the disease in most developing countries has not been updated for the last 125 years. Prizes could pave the way to develop a new and improved TB diagnostic.

Paul Wilson and Amrita Palriwala of Results for Development Institute (R4D) have studied the potential of prizes to spur the development of new health technologies, such as drugs, vaccines, diagnostics and medical devices, in the developing world. They spoke to their colleague Gina Lagomarsino about their forthcoming report “Prizes for Global Health Technologies,” which will be released next Tuesday, March 29th on R4D’s Center for Global Health R&D Policy Assessment website.

Gina: Why did you focus on prizes for diagnostics, as opposed to vaccines or drugs? Why TB diagnostics in particular?

Amrita: Our Center’s mission is to provide an evidence base for supporting ideas to advance technologies for neglected diseases. As we landscaped proposals, we found that proposals for prizes for new TB tests were among the most developed. Yet although prize competitions are well known in mathematics and other sciences, there is little experience using prizes to drive innovation in biomedicine. This lack of knowledge around how prizes work for health product development and global health in particular was the impetus for this work.

In general, diagnostics are a good testing ground for prizes because they present lower R&D costs and shorter development time frames than drugs and vaccines. There is great need for innovation in TB diagnostics, because the same sputum smear microscopy has been used to diagnose it for nearly a century in resource-poor areas.

Gina: Your report focuses on prizes for global health technologies. What is a prize, in the simplest terms and how have prizes been used in other contexts?

Paul: Prizes have waxed and waned in popularity, and they have a long history dating back to the 1800s. Several European countries in the second half of the 19th century considered removing the patent system entirely and replacing it with prizes. They can be a tool for promoting innovation, and in essence are a binding commitment to reward the completion of a goal, which is similar to policy innovations like priority review vouchers (PRVs) and advance market commitments (AMCs), which also reward success.

They mean different things to different people, which makes this an interesting area. People of different backgrounds and political persuasions want to use prizes to solve a range of problems. Retrospective prizes or recognition prizes like the Nobel Prize are important and certainly motivate scientists, but they don’t motivate people to solve a particular problem or to develop a particular product. Our report looks at prizes which are aimed at achieving specific objectives and of course our interest is health products.

Gina: What are some other mechanisms that have been used to incentivize innovation in global health? How do they compare to prizes?

Amrita: Push mechanisms like grants, product development partnerships (PDPs) and tax credits have been put forward—push funding is an input, but pull funding, like prize mechanisms, focuses on the outcomes. Push mechanisms shift the risk from the product developer to the sponsor.

Paul: Push mechanisms reduce the risk of product development by providing cash up front. Even regulatory changes that reduce the costs of clinical trials could also in this category. Pull mechanisms work on the other side of the equation and increase the reward.

Gina: Can a prize substitute for a market? How?

Paul: Currently, the motivation to invest in R&D is the market share that you access in the end. The size of that market, granted by the patent system, is the reward or the degree of the incentive to conduct R&D. For some prize proponents replacing this market or creating one from scratch is a primary goal and for others it’s not a goal at all.

The current patent system enables firms to charge substantially above what it costs to make the product, but this negatively impacts patients and governments. A prize could allow you to change the R&D investment decision by aligning incentives with public health needs instead of sales revenue. By substituting prizes for markets, where they don’t exist, or by asking firms to give them up, you ameliorate the problem of access.

Amrita: When we spoke to firms, it was hard for them to accept this equation. There needs to be a way to engage firms so that they can understand these alternate ideas. For TB diagnostics, a prize is not a substitute but a complement to the market – as it can help bring new minds and solutions to address the technological challenges with developing these tools.

There are different objectives for why people want to conduct prize competitions. The X PRIZE Foundation is trying to unlock latent markets, and the AMC is trying to substitute or create a market for a product that doesn’t naturally have one. Prize4Life, which recently awarded a biomarker prize to track the progression of ALS disease, is interested in reducing the technological barriers to carrying out R&D.

Gina: Prizes seemed simple until I read your report, which highlights the importance of design. What are important design considerations and how do they affect the prize?

Paul: The prize rises and falls on the technical specifications and the amount of the prize purse. One aspect of structure that we haven’t explored as much is the number of winners. Typically, you assume that there will be one winner—a so called “winner takes all competition,” but you could structure the prize to have multiple winners.

At first I was confused as to why firms view prizes so differently from markets, but they perceive prizes to be winner take all, which markets are not. Having multiple winners, akin to controlling a certain share of the market, would reduce the perceived risk for firms. This hasn’t been implemented before.

Another important dimension of structure is whether the prize provides a final end product payment or milestones payments. Of course, you can combine the two. Both pose risks to the sponsors. If you host a milestone prize, you may never actually get the final product in hand, but a final product prize may not be appropriate in all cases.

Gina: Did you find that prizes are an effective tool? If so, under what circumstances?

Paul: Prizes are helpful when you don’t know the way forward to answer an innovation question, and you have the sense that there are a lot of solvers out there who could help find the solution. This is what economists call information asymmetry. You don’t know who’s out there and what they’re thinking; if you did you could simply contract them directly.

Amrita: The other consideration is the market potential for the product. If it’s a large market, then a milestone prize might be sufficient, but if there’s little or no market, then you need a large final product prize or a milestone prize plus some subsidy. Our report lays out a decision tree which can help funders, policymakers, practitioners and others decide whether a prize is a useful tool for a particular innovation objective.

Paul: Very broadly, you need to think about who you’re trying to incentivize that’s not currently participating in the innovation space. Once you decide that, then you can systematically think through these questions. If there are only 3 organizations in the world that can solve a problem, then it may be better to engage them directly.

Tuesday, March 22, 2011

The Often Awesome Army

A guest blog post from our friends at the Often Awesome Army:

Our friend, Timothy LaFollette, is incredible. He is 30 years old and newly married. He is a phenomenal songwriter, a charismatic musician, a talented video editor, a fantastic cook and most of all, a really good person. He is also sick: stupid, unfair, scary and painful sick, which can't be fixed. In April 2009, at age 29, Tim was diagnosed with Amyotrophic Lateral Sclerosis - ALS (Lou Gehrig's Disease). At least five generations of Tim’s family have died from ALS, including his mother and grandmother, who both died within a year of their diagnosis.

Tim has a rare genetic strain, SOD1, which is a particularly ruthless subtype with a median survival rate of 12 months. Thankfully, Tim has survived his first diagnosis "birthday", and is approaching his second, but there have been no advances in treatment in the 28 years since his mother fell to the same illness. Tim is practically house-bound and has lost his ability to care for his basic needs.

There is a silver lining to this seemingly sad story. Because our Tim is one of the most open-hearted, pure and hilarious people we know, he's able to talk about his decline with phenomenal humor and truthfulness. Also, because our Timmy is also one of the kindest, most generous and charismatic people we know, he has an enormous community of friends fighting to make the rest of his life as wonderful as we possibly can.

We felt inexpressibly powerless and lost as we watched our amazing friend experience muscle spasms and then become increasingly clumsy. We witnessed him slowly lose his ability to move his limbs and then his respiratory function began to decline significantly, as he took shallower breaths and his voice became hoarse.

Born from an interest in caring for our friend, and supporting his wife, Kaylan, our group, the Often Awesome Army was created. Our "Army" started off as a small, close-knit group of friends. We made t-shirts, stickers and patches, and found ways to laugh through the sadness. We produced benefit rock shows and art auctions and raised money to help Kaylan buy a wheelchair accessible van, affectionately referred to as the ALSUV. We created a community of caretakers who stopped by Tim's house throughout the day, bringing him food, helping him bathe and toilet, and sometimes just to watch horror movies with him. As Tim’s illness progressed we formed the Core Care Team, of friends who volunteer their caregiving time and are trained on Tim’s equipment, to supplement the home nurse care that became constantly necessary.

Our Often Awesome Army has grown into a community of over 1,600 members. Scores of us have tattoos which signify solidarity with Tim. While each design is unique, all are based on a tattoo that Tim has on his arm: a flock of swallows that he got 10 years ago, to commemorate his mother’s passing from ALS. Like the formation of the army itself, the tattoos started off confined to a small tight-knit group of friends and eventually, people around the world have gotten tattoos in support of Tim. Many people with these tattoos had never had a tattoo before, like Tim’s ALS doctor from Duke, who proudly announced he was joining the army and going under the needle.

Tim realized early on that he had a responsibility to spread ALS awareness. This responsibility is to his family, the community of patients with ALS, their loved ones and to the larger population of people who don't even know about ALS. Though this disease affects a relatively small percentage of the population, and there is very little awareness, Tim refuses to die a silent death. ALS is not just a disease that attacked a baseball player 70 years ago; it is an ongoing struggle faced by thousands daily. Every 90 minutes, someone is diagnosed with ALS, and every 90 minutes, someone dies of ALS.

Tim's quest for spreading ALS awareness has resulted in Often Awesome: The Series, an award-winning web series about his journey with ALS. It features incredibly forthcoming interviews with Tim, his wife Kaylan, and members of the Often Awesome Army.

We invite you to watch the series, learn more about the Often Awesome Army, and support our efforts at

Monday, February 28, 2011

What is electrical impedance myography?

By now, we imagine you have heard the news (especially if you read our last blog entry or the New York Times) that the $1M ALS Biomarker Prize has been won. It was awarded to Dr. Seward Rutkove for his development of electrical impedance myography (EIM.)

But what exactly is electrical impedance myography?

Here's a blurb from The ALS Forum that provides some insight:

"Currently, researchers rely on death or use of a ventilator as the primary endpoints in ALS trials, measures too crude and slow to quantify drug effects early. The new test tracks disease progression with a noninvasive device that measures how electrical current travels through muscle, which degenerates as ALS progresses. Scientists can also measure muscle conductivity between needle electrodes implanted into muscle, but those methods are harder to perform and less reliable than the new device, besides being painful for patients. Rutkove's handheld device measures the electrical field generated when current runs through the muscles underneath electrodes placed on the skin.

The $16,000-$20,000 unit attaches to a laptop or personal digital assistant-like device. The test takes about 20 minutes and detects abnormalities even before a person notices muscle weakness. Rutkove has also suggested that electrical impedance myography might help doctors diagnose ALS, although it may not be able to distinguish ALS from other neurological conditions that affect muscle (Rutkove, 2009). The method does differentiate between neurogenic ALS and some myopathic conditions such as inflammatory myopathy (Garmirian et al., 2009)."

(If you haven't already, check out The ALS Forum, a great collection of the latest news and most up-to-date resources in the ALS field at

And here is a description of the technology in Dr. Rutkove's own words. After a 2009 review of potential ALS biomarkers published in The Lancet did not include a mention of electrical impedance myography, Dr. Rutkove wrote a letter to the editor that details his work and the potential impact of EIM.

Now, firmly in the limelight, Dr. Rutkove's technology is attracting interest from drug developers eager to make ALS clinical trials cheaper, faster, and more efficient. Dr. Rutkove has co-founded Convergence Medical Devices to create and market a version of the technology that can easily be used in clinical settings.

And while this biomarker has no direct therapeutic value, it holds the promise of accelerating the discovery of treatments or a cure for this disease--the mission of Prize4Life and the hope of thousands of patients and families around the world.

Wednesday, February 16, 2011

$1M ALS Biomarker Prize Has Been Won!

In 2006, the founding members of Prize4Life organized a conference with some of the leading minds of the ALS research community and the biotechnology industry to answer a simple question: why, after more than 140 years since it was first described in scientific literature, is there still no effective treatment for ALS?

Participants at the conference identified several key challenges in the field, but perhaps the most fundamental obstacle that had yet to be overcome was the need for a biomarker, a tool that could reliably track the progression of the disease in patients during clinical trials. Because the progression of ALS is highly variable among individuals, the only ways that researchers could gauge whether a potential treatment was having any effect was to measure survival time or use a subjective survey of a patient's ability to walk, talk, speak, and swallow. The ambiguity of these measurements meant that clinical trials needed to enroll a large number of patients and last for a long period of time. Expensive and often inconclusive clinical trials meant that industry had little incentive to invest in drug development and any progress in research would be painstakingly slow.

Prize4Life now had a clear objective. In 2006, we partnered with the open innovation platform InnoCentive to launch the $1M ALS Biomarker Prize with the goal of identifying a biomarker that could more sensitively track the progression of ALS and dramatically reduce the cost of clinical trials. It was our intention to catalyze a breakthrough, a leap forward in ALS research that would accelerate the development of a treatment for the thousands upon thousands of people battling this disease across the globe.

Now, five years later, we are proud to announce that a breakthrough has been achieved. Our Scientific Advisory Board, made up of the top minds in the ALS research and biotechnology communities, unanimously voted to award the million-dollar prize to Dr. Seward Rutkove, a neurologist at Beth Israel Deaconess Medical Center in Boston. The New York Times profiled Dr. Rutkove and the Prize4Life award.

Dr. Seward Rutkove’s biomarker, using a method called electrical impedance myography (EIM), sensitively measures the flow of a small electrical current through muscle tissue. The current travels differently through healthy and diseased tissue, and by comparing the size and speed of the electrical current, EIM can accurately and efficiently measure the progression of the disease. Read more about the EIM technology here.

EIM technology in use. Photo credit: Convergence Medical Devices

This biomarker will make ALS clinical trials cheaper, faster, and more efficient; effectively cutting the overall cost of these trials in half, creating an incentive for industry to invest in ALS, and accelerating the progress of potential therapies through the drug development pipeline.

The development of Dr. Rutkove's biomarker is not only a game-changer for ALS research, it is a validation of the prize model's role in driving biomedical innovation. The $1M ALS Biomarker Prize is the largest prize ever awarded in response to a specific medical challenge. The million-dollar purse leveraged more than $4M in investment from teams competing for the prize. And more than 1000 solvers from over 20 countries signed up for the challenge, bringing new minds and new ideas into the fight against ALS. You can learn more about the impact of the prize on biomarker research here.

Now, we at Prize4Life are turning our attention to overcoming the next obstacle: the identification of promising drugs that can slow the progression of ALS. It is the focus of our second million-dollar challenge, the $1M ALS Treatment Prize.

We invite you to learn more about Prize4Life and join our efforts as we continue the march toward a cure.