The goal of the BforSMA study was to identify potential biomarkers, or a panel of biomarkers, that could be used as measures of SMA disease severity and might also be used to assess drug efficacy and shorten the duration of clinical trials. At 18 clinical sites across North America, a cross-sectional single, evaluation of blood and urine was performed in 108 pediatric patients with SMA between the ages of 2 and 12 years old, as well as 22 age-matched control subjects.

The “Candidate Proteins, Metabolites and Transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study” by Richard Finkel MD et al. described a prospective biomarker discovery effort that identified analytes associated with a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS), and a number of secondary clinical measures. A total of 200 candidate biomarkers correlated with MHFMS scores: 97 plasma proteins, 59 plasma metabolites and 44 urine metabolites markers.The “Evaluation of SMN Protein, Transcript, and Copy Number in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study” by Thomas Crawford MD et al. reported on the relationship between SMN protein, transcript level and SMN2 copy number. Additionally, the study evaluated whether these SMN measurements are associated with SMA clinical type, motor function and age.

The complete datasets from these studies are available through the publicly accessible SMA Biomarkers database at http://neuinfo.org/smabiomarkers/.

As a result of the BforSMA study discovery effort, a panel of 27 validated plasma protein biomarkers was created by Myriad RBM in collaboration with the SMA Foundation. The SMA-MAP panel is now available at Myriad RBM.

The biomarkers identified through the BforSMA studies may provide SMA researchers with a quantitative tool to measure disease progression and the efficacy of potential therapeutics for SMA.

If you are interested in a selection of recent articles published in the SMA field, please go to http://www.smafoundation.org/research/library/.  

NEW YORK, NY– April 3, 2012 – The Spinal Muscular Atrophy (SMA) Foundation announced today the launch of a biomarker assay panel for SMA using Myriad RBM’s Multi-Analyte Profiling (MAP) technology platform. The SMA-MAP panel is designed to evaluate the severity of SMA and disease progression and can be used to assess drug efficacy and shorten the duration of clinical trials for SMA therapeutics.

The SMA Foundation initially provided more than 120 plasma samples from SMA patients collected in the Biomarkers for SMA (BforSMA) clinical study for processing on Myriad RBM’s DiscoveryMAP^® 250+ biomarker discovery platform.  Analysis of this data revealed a set of candidate biomarkers which were then tested against over 150 longitudinal samples from an SMA natural history study by the Pediatric Neuromuscular Clinical Research Network.  A panel of 27 validated biomarkers was selected, and is now being made available to clinical researchers by Myriad RBM as a new product to be called SMA-MAP.   Measuring these biomarkers in SMA clinical trials may help researchers to efficiently predict and monitor SMA progression and therapeutic efficacy.

“Myriad RBM has given us a tool that holds great promise.” said Karen S. Chen, Ph.D., Chief Scientific Officer and Chief Operating Officer of the SMA Foundation. “We are now able to make biochemical measurements that will help us objectively assess functional changes in children and adults with SMA, and, hopefully, detect early signals of therapeutic success in new drug trials for this devastating disease.”

“Research on orphan diseases like SMA is typically underfunded.  As a result, the development of effective therapies and treatments proceeds slowly and is insufficient to address the critical need for children and families affected by medically devastating illnesses like SMA,” said Craig Benson, President of Myriad RBM. “SMA researchers now have access to a quantitative and reliable tool that links biomarker results with complex disease symptoms and characteristics.  We are confident that the use of the SMA-MAP will play an important role in accelerating development of SMA therapeutics.”

ABOUT SPINAL MUSCULAR ATROPHY

Spinal Muscular Atrophy (SMA) is a motor neuron disease and the leading genetic cause of death among infants and toddlers. Characterized by selective loss of nerve cells in the spinal cord, the disease leads to increasing muscular weakness and atrophy. Patients afflicted by SMA lose muscle control and strength, leading to progressive inability to walk, stand, sit up and breathe, depending on the severity of the disease. It is estimated that approximately 1 in 6,000 -10,000 infants are born with SMA.

ABOUT THE SPINAL MUSCULAR ATROPHY FOUNDATION

Founded in 2003, the Spinal Muscular Atrophy Foundation is a nonprofit organization dedicated to accelerating progress towards a treatment for Spinal Muscular Atrophy through targeted funding of clinical research and novel drug development efforts. Since its inception, the Foundation has awarded over $100 million for SMA research. In addition, the Foundation is committed to raising awareness and generating support for increased research efforts in SMA among the leaders of industry and government. For more information, visit the SMA Foundation website at www.smafoundation.org.

Contact:

SMA Foundation
Dione Kobayashi
dkobayashi@smafoundation.org
646-253-7100

Both pieces of legislation are supported by a wide constituency including the National Organization for Rare Disorders (NORD) and the Biotechnology Industry Organization (BIO). Text from NORD’s press release on the acts is attached below.

John Maraganore (a BIO board member and the CEO of Alnylam) provided testimony to the House Committee on Energy & Commerce, Subcommittee on Health in support of the FAST act on March 8, 2012. The full testimony is attached below– on page 6, SMA is discussed as a rare disease that could benefit from this legislation. http://republicans.energycommerce.house.gov/Media/file/Hearings/Health/20120308/HHRG-112-IF14-WState-MaraganoreJ-20120308.pdf
Jonathan Leff (a board member of BIO and the SMA Foundation) along with a number of SMA clinicians and researchers provided background information on SMA for the testimony.

NORD Supports FAST Act Introduced by Representatives Stearns and Towns

Bill to Expedite Development of Therapies for Patients with Unmet Medical Needs

WASHINGTON DC—–The National Organization for Rare Disorders (NORD) supports proposed legislation introduced this week by Representatives Cliff Stearns (R-FL) and Edolphus (Ed) Towns (D-NY) to accelerate the development of innovative therapies for people with serious or life-threatening diseases.

H.R. 4132, Faster Access to Specialized Treatments or the FAST Act, is designed to modernize and expand the Food and Drug Administration’s Accelerated Approval pathway to encompass a broader range of diseases and encourage innovative drug development tools and strategies.

“We applaud Representatives Stearns and Towns for their leadership in introducing this much-needed legislation,” said NORD President and CEO Peter L. Saltonstall.  “There are millions of Americans with rare diseases who have no FDA-approved treatment.  Accelerating the development of safe, effective therapies for these patients is a top priority for the rare disease community.”

Saltonstall said Stearns and Towns have listened to the concerns of patients and have responded with legislation that will speed the approval of new therapies for patients with serious and life-threatening diseases, while also maintaining FDA’s high standards for safety and efficacy.  He said the bill also provides further clarity of the FDA approval process by codifying and modernizing the well-established Accelerated Approval program.

NORD also supports legislation introduced by Senator Kay Hagan (D-NC) in the U.S. Senate recently known as the TREAT Act.  The Senate bill also is intended to enhance and expand the Accelerated Approval process, with additional provisions to promote development of treatments for unmet medical needs.

“Accelerated Approval” refers to a pathway at FDA that allows for earlier approval of drugs for serious, unmet medical need based on a surrogate endpoint or marker predicting clinical benefit.  Subsequent testing must be done to verify the anticipated benefit.

Of the approximately 7,000 rare diseases, only about 250 currently have treatments approved by FDA.  In the U.S., a disease is considered rare if it affects fewer than 200,000 Americans.

NORD represents the nearly 30 million Americans who have rare diseases.  More than half of these patients are children, and most rare diseases are serious, life-altering or even life-threatening diseases.

New York, NY, February 21, 2012 – The Spinal Muscular Atrophy (SMA) Foundation will join the National Organization for Rare Disorders (NORD) and others around the world in observing Rare Disease Day on February 29.  The purpose is to focus attention on the needs of patients and families affected by rare diseases.

“This is a global observance,” said Peter L. Saltonstall, president and CEO of NORD.  “Individuals and organizations around the world will all be sharing stories of how rare diseases affect their lives.”

The challenges of living with a rare disease, he said, include:

• Difficulty getting a timely, accurate diagnosis
• Too little research
• Too few treatments
• Reimbursement or other issues affecting access to treatments
• A sense of isolation
• Difficulty finding medical experts

In the U.S., any disease affecting fewer than 200,000 Americans is considered rare.  According to the National Institutes of Health (NIH), there are nearly 7,000 such diseases affecting nearly 30 million Americans.

Studies have shown that it often takes five years or longer to get an accurate diagnosis of a rare disease.  In addition, only about 200 of the diseases classified as rare have approved treatments.

Rare Disease Day started in Europe in 2008.  It was launched by EURORDIS (Rare Diseases Europe).  Last year, it was observed in more than 60 countries, with a national sponsor in each country.  NORD is the sponsor in the U.S.

More than 500 patient organizations, government entities, research institutions, and companies developing treatments have signed up as Rare Disease Day Partners on the national website hosted by NORD (www.rarediseaseday.us).  The SMA Foundation is one of those partners.

Each year, a global planning team selects a theme for Rare Disease Day.  The theme for 2012 is “Rare but strong together.”

Rare Disease Day activities in the U.S. will include a “Handprints Across America” campaign to create a gallery of photos on the Rare Disease Day website; educational materials for classroom teachers; and a nationwide blitz of patient photos, stories and videos to increase awareness of specific rare diseases and the challenges of living with a rare disease.

Several special events are planned, including a scientific symposium at the National Institutes of Health (NIH) and a Rare Disease Patient Advocacy Day at the Food and Drug Administration (FDA).

“Since many of these diseases are genetic, more than half of the people who have rare diseases are children” Saltonstall said.  “The problems encountered by families are enormous.  It’s important for these families to know they are not alone.”

About the Spinal Muscular Atrophy Foundation
Founded in 2003, the Spinal Muscular Atrophy Foundation is a nonprofit organization dedicated to accelerating progress towards a treatment for Spinal Muscular Atrophy through targeted funding of clinical research and novel drug development efforts. Since its inception, the Foundation has awarded over $100 million for SMA research. In addition, the Foundation is committed to raising awareness and generating support for increased research efforts in SMA among the leaders of industry and government. For more information, visit the SMA Foundation website at www.smafoundation.org.

About NORD
NORD was established in 1983.  It provides advocacy, education, research and patient services on behalf of rare disease patients, families, and patient organizations.

In the pantheon of companies competing in the health care market, Proteus Biomedical is unique. A start-up based in Redwood City, Calif., Proteus has developed technology to attach a biodegradable digital device to a pill. After a patient swallows the pill, it transmits data on the body’s interaction with the medication.

Although the system sounds like the stuff of science fiction, one of the company’s first major partners was the venerable Swiss drugmaker Novartis. In 2010, the two agreed to investigate applications for the California firm’s digital device and monitoring system, which transmits information from a patient’s iPhone or similar handheld device to physicians and others, such as family involved in a patient’s care, via the Internet. Proteus also has prospective deals with other big drug companies.

In recent months, drugmakers have been entering collaborations with information technology firms, electronics companies, health insurance providers, and others they have never before partnered with. Their motivation is partly to fill their pipelines and partly to develop businesses that are not tied to patented drugs. These partnerships illustrate a new reality confronting big pharma: In the age of personalized health care, companies must look outside their own walls for the patient data and technology necessary to grow.

“Since last fall, I’ve noticed a greater sense of urgency and inevitability on the part of pharmaceutical companies with respect to the fact that health care is really shifting,” says Carolyn Buck Luce, global pharmaceuticals sector leader for the consulting firm Ernst & Young.

According to Buck Luce, the shift is toward obtaining data that will provide drugmakers access to a “lifelong relationship” with patients—data far beyond what are amassed in a traditional clinical trial. In an indication of how far afield the sector is moving from its traditional strategic base, Buck Luce points to the business model Starbucks first brought to investors: the coffee house as a “third place,” on par with the home and the office, where people feel a particular level of social satisfaction.

“We are talking about the third places in health care,” she says. “We are seeing an inexorable shift in the epicenter of the health care system beyond the existing pillars of the hospitals and the doctors’ offices to wherever the health care consumer is—the home, the community clinic, the car.” With solid connections to the two traditional pillars, big pharma wants to connect to the third.

She points to Proteus’ partnership with Novartis as particularly forward-looking. “What can companies like Novartis and Proteus do together?” Buck Luce asks. “One thing or many things?” What matters, she says, is that a drug company is acting now to see how the Proteus chip can be used and how patient data heretofore excluded from research may guide drug development and marketing.

David O’Reilly, Proteus’ chief product officer, says the firm’s partnerships focus on its raison d’être: exploring the possibilities of digitalized personalized medicine. “How does one invent and innovate and advance novel digital technology to embed into existing medical products?” O’Reilly asks. “How do we do the same thing in the health care industry that we have seen in other industries, where physically tangible products in our lives are becoming smart?”

Although smart drugs and smartphones have obvious differences, Proteus sees a benefit in hooking the two together. The link will provide drugmakers with data on how their products are working. “There is a gap between the efficacy of drug design and the effectiveness of drugs in the real world,” O’Reilly says.

Proteus’ product has three components: a self-powered digital sensor called an ingestible event marker (IEM) that is glued to a pill; a nonmedicated skin patch sensor that is like a drug delivery patch; and a cell phone application that monitors and transmits data. After being swallowed, the IEM can transmit information on type of drug, time of dose, and heart and respiratory rate to the skin patch, which in turn sends it to the cell phone.

“We want to find fellow travelers and early adopters who share our strategic vision of what the world [of digital health care] might become and work with them on making it happen,” O’Reilly says. He notes that the company’s most recent partnerships are with Lloyds Pharmacy, in England, to market smart pills, and consumer products company Avery Dennison, to develop products associated with the skin patch sensor. Together with the Novartis deal, the partnerships cover a lot of territory in the health care market, O’Reilly says.

Under a licensing and research collaboration with Proteus, Norvartis is currently evaluating the technology on unspecified medicines. “The goal of combining a Novartis drug with the Proteus system is to understand patients’ medication-taking behavior, potentially improving adherence and compliance to therapies—a critical factor for achieving better patient outcomes and to enable patients to better communicate with physicians and caregivers,” says Beth Calitri, a media relations representative with Norvatis.

Monitoring patient behavior is also behind a partnership between Sanofi and AgaMatrix, a Salem, N.H.-based developer of blood glucose monitors. In 2010, the two firms signed a 10-year agreement under which the drug company, a major insulin supplier, began marketing AgaMatrix’ standard blood glucose meter, BGStar. The companies recently began marketing the first product developed under the agreement, iBGStar, which connects the meter to an iPhone. The iPhone can retrieve and archive information or e-mail it to health care providers involved in the patient’s treatment.

Sanofi, of course, is still looking for pharmaceutical breakthroughs in the laboratory, but in nontraditional ways. Last month, for example, with the venture capital firms Third Rock Ventures and Greylock Partners, it launched Warp Drive Bio, which will use genomics to guide natural product drug discovery. Warp Drive’s technology was developed by Harvard University scientist Gregory L. Verdine, a partner at Third Rock.

A new kind of academic partnership is also playing a key role in Sanofi’s quest to access scientific expertise, says Shiv Krishnan, Sanofi’s senior director of partnering and innovation.
“In the past, one way of continuing to feed the pipeline was to in-license products—a pure business development play,” Krishnan says. “Now, as science becomes more complex and diseases need to be better defined as challenges, we are continually adapting our strategies to be smarter in the way we partner. We want to build strategic alliances with academia, for example, to better understand how certain drugs for a human indication can be developed and to bring in a more medical and academic perspective to augment the scientific value of the project.”

Sanofi has tried to maximize input by dealing with networks of institutions rather than committing to projects with individual universities or labs. Krishnan points to the firm’s collaboration with a group of California institutions—including Scripps Research Institute, California Institute of Technology, Stanford University, and the University of California, San Francisco—in research areas such as regenerative medicine and protein engineering.

“Essentially, we are tapping into the innovation at the institution,” Krishnan says. “We may not have a specific application for it, but we are moving into an area where a convergence of different disciplines will be the source of innovative drugs—a convergence between biomaterials and pharmaceuticals, a convergence between cell engineering and therapeutics, a convergence between devices and biologics. It’s a different way of developing drugs.”

Sanofi is “evolving from a pure pharmaceutical company developing small molecules to more of a health care company,” Krishnan explains. Rather than simply delivering a drug, he says, Sanofi’s goal is to help patients better understand their diseases. “We are looking to grow our business to be sustainable and global, and not to be tied to cycles imposed on us by patent expiry,” he says.

The premium on information residing outside big pharma R&D departments is also reflected in new alliances with patient advocacy groups. A three-way spinal muscular atrophy (SMA) drug partnership among PTC Therapeutics, Roche, and the SMA Foundation illustrates the clout—both financial and scientific—that patient groups now wield.

The foundation approached PTC in 2006 to see what the biotech firm could do to target SMA with a technology PTC calls gene expression modulation by small molecules, or GEMS. PTC had already deployed GEMS against Duchenne muscular dystrophy, cystic fibrosis, and other diseases. “They started out giving us a small grant and then went to a larger grant that got us to a near-development candidate and a partnership with Roche,” says PTC’s chief executive officer, Stuart W. Peltz.

Yet the deal with Roche didn’t end the alliance with the SMA Foundation. For both PTC and Roche, the advocacy group brings a long-standing relationship with patients and their physicians, Peltz says. “SMA Foundation has done a good job understanding the natural history of the disease. They are a good partner from the standpoint of understanding the disease itself.”

Luca Santarelli, head of central nervous system clinical R&D at Roche, agrees. “The three-party collaboration is quite unique but also very welcome because of SMA’s deep scientific foundation,” he says. “They bring the link to the patient and to the clinical investigator in this very specialized area.” Looking ahead to later-stage development, “they have the skills to conduct trials more efficiently and more in tune with what the patient needs.”

Just as SMA Foundation got PTC busy on the disease, Santarelli notes, the collaboration between those partners got Roche off the dime in an area that it might not normally have pursued. Patient information was the enticement. “The foundation lowered the hurdles with evidence that the disease can be approached with therapeutics,” he says.

Nontraditional partnerships will become more prominent in the years ahead as drug companies act on their growing awareness that the information they need to expand resides outside their corporate walls, Santa¬relli adds. “Roche only has a limited amount of capability,” he says. “More and more we are realizing that we have to go outside for innovation.”

Even the world’s biggest drug company, Pfizer, has forged nontraditional links in pursuit of patient information. Last October, it announced partnerships with the insurance provider Humana and the pharmacy benefits management firm Medco Health Solutions. With Humana, Pfizer is investigating ways to reduce inefficiencies in getting drugs to patients with chronic problems including pain, cardiovascular disease, and Alzheimer’s disease. Researchers at Medco’s United BioSource Corp. (UBC) subsidiary, meanwhile, are investigating genomics-based, personalized-medicine approaches to improving the design and administration of therapies.

James Harnett, senior director of U.S. health economics and outcomes research at Pfizer, says the partnerships “provide us an opportunity to identify where the unmet need is and find where we can bring a solution to the table.” Humana and Medco both generate information about patients and “real world” success and failure of drugs.

Use of such data, Harnett says, marks a change in big pharma’s approach to R&D, which has traditionally focused on a drug’s performance in the clinic. But with regulators and insurance providers demanding that companies demonstrate a drug candidate’s benefit compared with what is already on the market, pharmaceutical researchers are hungry for detailed information on how individual patients respond to therapy.

“Any forward-looking drug company is paying attention to personalized medicine,” says Robert S. Epstein, chief clinical R&D officer at Medco and president of UBC. He says benefits management firms also have an interest in increasing the effectiveness of therapies. This interest was behind Medco’s 2010 acquisition of UBC, a research company with expertise in drug safety and health care economics.

Since the UBC acquisition, Medco has signed contracts with Sanofi and AstraZeneca with the goal of bringing the insights of its clients—insurance companies, often called payers—into the R&D lab at big pharma, according to Epstein. But the Pfizer deal, he says, is unique in its focus on personalized medicine. Harnett adds that the collaboration is intended to enhance Pfizer’s precision medicine approach, which leverages genomic and phenotypic information to investigate the underlying biology of disease and identify patients most likely to benefit from a new drug.

“We cover 65 million patients,” Epstein says. “We have a lot of payers who are very excited about having their membership participate in these kinds of research studies. So we are providing real-world access to patients, payers, and doctors.”

Similarly, Humana hopes to influence drugmakers’ R&D pipelines to better meet the needs of patients with chronic diseases, according to William Fleming, vice president of Humana’s pharmacy solutions division. Humana’s Competitive Health Analytics subsidiary is working with Pfizer researchers on “retrospective” research, using available data on patients to learn how well drugs performed. But the partners may advance to collaborating in the clinic.

Humana will announce a second partnership with a major drug company soon and anticipates a third one by the end of the year, Fleming says. In the end, he hopes to sign on with eight to 10 drug companies.

An evolution is under way in the strategy rooms at big pharma, Medco’s Epstein says. “In the last two years or so it has been dawning that the way drugs or medical interventions work in the real world is different than in clinical trials,” he says. “I don’t think the drug companies paid attention to it previously because they didn’t have to.”

Five years ago, Epstein says, the discovery of a new biological pathway could yield a drug that would be reimbursed under insurance programs whether or not it was better than existing therapies or likely to improve patient compliance. “It didn’t matter. Innovation just got reimbursed,” he says. “But now people are saying, ‘Great, I’m glad you found a new target or pathway, but if you don’t show me how current therapies are working in the real world—where the problems are and where yours is better—we are not so interested.’ ”

It’s a fair assessment, Pfizer’s Harnett says, and a reason Pfizer is pursuing patient-focused data. Drug companies and the payers are “realizing that there is a tremendous challenge out there with escalating health care costs,” he says, and they “will continue to foster new collaborative partnerships—expanding to the regulatory agencies as well.”

Research initiatives in areas such as opiates abuse, infectious diseases, and vaccinations will bring together drug companies, benefits management firms, and regulators to pool data, Harnett predicts. “We are on the edge of something that will very much be an opportunity for everyone involved,” he says. “The real impact is for patients. I can’t think of a better time for us to focus on that.”

By Rick Mullin

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2012 American Chemical Society
 

The lack of treatment for SMA is something that the New York-based SMA Foundation is working to change; here the aim is to speed up the development of a pioneering treatment for the disease.

Dione Kobayashi is a Director at the SMA Foundation. Her role there is to oversee the development of biomarker tools and protocols for SMA as well as managing the Foundation’s in vivo drug testing pipeline. She tells me it was the apparent tangibility of an SMA cure that drew her to the study of this disease…

“I have been involved in neurodegeneration research for a number of years. My doctoral studies at the University of Edinburgh, and much of my prior industry work, were on Alzheimer’s and Parkinson’s disease. These are well-known disorders that are generally not caused by single genetic mutations and there are still many unknowns as to how people get these diseases – unlike SMA.”

“I learned about SMA from a former colleague of mine after they joined the SMA Foundation.  As I discovered more about the unique genetics of SMA – which is caused by the loss of a single gene SMN1 – I was deeply intrigued because it seemed that it was conceptually ‘curable’. This concept is possible due to the presence of a nearly identical ‘backup’ gene called SMN2 that could be targeted for upregulation. Working on SMA thus creates an ideal situation, where a scientist is engaged on an elegant problem that appears to have a biologically built-in rescue system.” The potential to manipulate this natural, but currently flawed rescue system (a lot of SMN2 is expressed as the unstable SMNΔ7) she says, “Will help to find treatments and save and improve the lives of thousands of children.”

In August last year, Kobayashi and her colleagues published a paper describing the development of a sandwich ELISA kit for the detection of SMN protein in blood  – specifically, in samples of peripheral blood mononuclear cells (PBMCs).

This assay is a significant advancement in SMA research due to the critical lack of a biomarker-based method to assess potential SMA therapies. Despite several prospective treatments for SMA being under evaluation at present, their efficacy is difficult to assess with current diagnostic tools.

Though several other groups have developed useful laboratory assays for SMN, Kobayashi explains why the SMA Foundation-developed ELISA kit has an advantage in the clinical area:

“This particular ELISA has gone through quality control processes in an effort to ensure that each off-the-shelf kit can produce robust and reproducible results. Also, the assay has been shown to be useful for a number of different in vitro and in vivo applications with both human and mouse cells and tissues.”

Essentially, the kit has general translational applicability to both preclinical and clinical research. In other words it could speed-up the “bench to bedside” journey of any prospective treatments from lab to clinic. This, as mentioned previously, is the main goal of the SMA Foundation as Kobayashi explains:

“Our mission at the SMA Foundation is to accelerate the development of therapies for SMA. SMA causes devastating weakness in patients and in its more common and severe form, death occurs often by the age of two; while in milder forms SMA causes progressive and debilitating physical disabilities. While there is no current effective treatment available, there are several new drugs in clinical trials or entering the clinic in the next couple years. The Foundation staff is focused intently on these trials and much of our work revolves around development of tools and outcome measures that will help determine if an experimental drug is effective. My work specifically involves the development and validation of blood-based biomarkers for SMA, and it is our hope that the SMN ELISA will be part of the biomarker toolkit for several of these trials.”

Involved in the SMA Foundation kit’s development was Proteintech antibody 11708-1-AP, an anti-SMN rabbit polyclonal IgG. The antibody was of several screened by Kobayashi and her team intended to increase the sensitivity of the assay:

“When we screened 11708-1-AP, we found that it bound recombinant SMN antigen at a concentration that was nearly four times lower than the other antibodies tested. This allowed us to improve the sensitivity of the assay significantly and gave us an ELISA that we felt comfortable would give robust and reliable measurements.”

So would Dr. Kobayashi recommend the 11708-1-AP antibody? “The antibody has performed well, and also seems to bind to an epitope that differentiates it from several other commercially available SMN antibodies. I would recommend it, especially for researchers exploring new SMN assays themselves.”

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Biogen Idec and Isis Pharmaceuticals Announce Global Collaboration for Antisense Program Targeting Spinal Muscular Atrophy

– Biogen Idec has Option to Develop and Commercialize Promising Compound for Most Common Genetic Cause of Infant Mortality –

– Biogen Idec’s Expertise in Neurology to Aid in Rapid Development of ISIS-SMN_Rx – 

SMA is a genetic neuromuscular disease characterized by muscle atrophy and weakness, and it is the most common genetic cause of infant mortality. One child out of every 10,000 births worldwide is born with SMA. Children with SMA generally appear normal at birth, with symptoms developing as early as a few months after birth, and in the most severe form of the disease, children have a significantly shortened lifespan. Isis’ ISIS-SMNRx is designed to compensate for the underlying genetic defect that causes SMA.WESTON, Mass. and CARLSBAD, California – January 4, 2012 – Biogen Idec (NASDAQ: BIIB) and Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today announced that they have entered into an exclusive, worldwide option and collaboration agreement under which the companies will develop and commercialize Isis’ antisense investigational drug, ISIS-SMNRx, for the treatment of spinal muscular atrophy (SMA).

Under the terms of the agreement, Isis will receive an upfront payment of $29 million and is eligible to receive up to $45 million in milestone payments associated with the clinical development of ISIS-SMNRx prior to licensing. Biogen Idec has the option to license ISIS-SMNRx until completion of the first successful Phase 2/3 trial. Isis could receive up to another $225 million in a license fee and regulatory milestone payments. In addition, Isis will receive double-digit royalties on sales of ISIS-SMNRx. Isis will be responsible for global development of ISIS-SMNRx through the completion of Phase 2/3 registrational clinical trials, with Biogen Idec providing advice on the clinical trial design and regulatory strategy. If Biogen Idec exercises its option, it will assume global development, regulatory and commercialization responsibilities.

“SMA is a heartbreaking disease – it can kill children before their 2nd birthday and there are currently no therapies to treat the disease,” said George A. Scangos, Ph.D., CEO of Biogen Idec. “It is exactly the kind of disease and program that we are focused on at Biogen Idec. The unmet need could not be any greater, the program fits with our mission to bring innovative therapies to patients with serious neurologic diseases, and Isis’ antisense compound has the potential to be a highly effective, first-to-market therapy for this deadly disease. We have the utmost respect for Isis’ scientific leadership and expertise in antisense technology, and we have crafted a collaboration that brings together our two companies’ strengths toward a common goal.”

“Biogen Idec’s expertise in the global development and commercialization of innovative new therapies for neurologic diseases is a great strategic fit to advance ISIS-SMNRx,” said Stanley T. Crooke, M.D., Ph.D., Chairman of the Board and Chief Executive Officer. “This alliance is consistent with our business strategy to develop antisense drugs to proof-of-concept with a knowledgeable partner that is committed to supporting the rapid development of the drug. Given the severity of the unmet need in SMA, our proof-of-concept studies should also serve as the registrational trials for ISIS-SMNRx. We believe that, together with Biogen Idec, we will be able to expeditiously develop this investigational drug in hopes of bringing to market an effective and desperately needed treatment to improve the lives of children with SMA.”

About SMA
SMA is a severe genetic disease that affects approximately 30,000-35,000 patients in the United States, Europe and Japan. One in 50 people, the equivalent of about 6 million people in the United States, are carriers of the SMA gene. Carriers experience no symptoms and do not develop the disease. However, when both parents are carriers, there is a one in four chance that their child will have SMA. SMA is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene leading to a decrease in the survival motor neuron (SMN) protein. SMN is critical to the health and survival of nerve cells in the spinal cord responsible for neuromuscular growth and function. The severity of SMA correlates with the amount of SMN protein. Infants with Type 1 SMA, the most severe form of the disease, produce very little SMN protein and have a life expectancy of less than two years. Children with Type II have greater amounts of SMN protein but still have a shortened lifespan and are never able to stand independently. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow. 

About ISIS-SMNRx
ISIS-SMNRx is designed to treat all types of childhood SMA by altering the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. The United States Food and Drug Administration granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA. In December 2011, Isis initiated the first Phase 1 clinical study evaluating ISIS-SMNRx in children with SMA. The Phase 1 study is a single-dose, dose-escalation study designed to assess the safety, tolerability and the pharmacokinetic profile of the drug in children between the ages of 2 and 14 who are medically stable. In this study, ISIS-SMNRx will be administered intrathecally as a single injection directly into the spinal fluid. Isis plans to follow this study with a Phase 1 multiple-ascending dose study.

Isis acknowledges support from the following organizations for ISIS-SMNRx: Muscular Dystrophy Association, SMA Foundation, Families of SMA and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School.

About Biogen Idec
Through cutting-edge science and medicine, Biogen Idec discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, hemophilia and autoimmune disorders. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates nearly $5 billion in annual revenues. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

About Isis Pharmaceuticals
Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners. Isis’ broad pipeline consists of 28 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic and severe and rare/neurodegenerative diseases, and cancer. Isis’ partner, Genzyme, plans to commercialize Isis’ lead product, mipomersen, following regulatory approval, which is expected in 2012. Isis’ patents provide strong and extensive protection for its drugs and technology. Additional information about Isis is available at www.isispharm.com.

Biogen Idec Safe Harbor Statement
This press release contains forward-looking statements, including statements about product development and commercialization. These forward-looking statements may be accompanied by such words as “anticipate,” “believe,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “will” and other words and terms of similar meaning. You should not place undue reliance on these statements. Drug development and commercialization involve a high degree of risk. Factors which could cause actual results to differ materially from current expectations include the risk that adverse safety events may occur, regulatory authorities may require additional information or may fail to approve any potential new therapy, product reimbursement may be limited or unavailable, there may be problems with manufacturing processes, intellectual property rights may not be adequately protected, and the other risks and uncertainties that are described in the Risk Factors section of Biogen Idec Inc.’s most recent annual or quarterly report and in other reports Biogen Idec Inc. has filed with the SEC. These statements are based on current beliefs and expectations and speak only as of the date of this press release. Biogen Idec Inc. does not undertake any obligation to publicly update any forward-looking statements.

Isis Safe Harbor Statement
This press release includes forward-looking statements regarding Isis’ strategic alliance with Biogen Idec, and the discovery, development, activity, therapeutic potential and safety of ISIS-SMNRx. Any statement describing Isis’ goals, expectations, financial or other projections, intentions or beliefs, including the planned commercialization of mipomersen, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Isis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis’ programs are described in additional detail in Isis’ annual report on Form 10-K for the year ended December 31, 2010 and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.

Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.

Bloomberg News
by Robert Langreth
January 4, 2012

Biogen Idec Inc. (BIIB) will gain Isis Pharmaceuticals Inc. (ISIS)’s drug for an inherited muscle-weakening disease that afflicts children, in a development deal that may cost as much as $299 million.

Biogen, the world’s biggest maker of multiple sclerosis drugs, will pay Isis $29 million now, plus $45 million in possible milestone payments, and gain an option to license the experimental medicine for spinal muscular atrophy after completion of a successful efficacy trial, the companies said today in a statement. If Biogen exercises the option, Carlsbad, California-based Isis may get $225 million more, plus royalties on sales if the drug is approved.

The deal vaults Weston, Massachusetts-based Biogen to the forefront of a race to develop the first drug for the inherited disease that afflicts 9,000 people in the U.S., according to the Spinal Muscular Atrophy Foundation. Severe versions of the disease kill children a few years after they are born. Novartis AG (NOVN) and Roche Holding AG (ROG), both based in Basel, Switzerland, are also testing drugs for the disease.

“I am very, very excited about this compound,” said Alfred Sandrock, a senior vice president at Biogen, in a telephone interview. If successful, “it would be a breakthrough, the first of its kind; it is exactly the kind of thing we are looking for.”

Missing Gene
“Children with spinal muscular atrophy lack a gene for a protein called SMN that is necessary for proper nerve cell development. The Isis drug, which began human trials in December, is injected into the spinal fluid and seeks to boost levels of the SMN protein,” Sandrock said.

“This has the potential of being truly transformative, if the preclinical data are in any way reflected in the outcome of clinical studies,” said Darryl De Vivo, a pediatric neurologist at Columbia University Medical Center, in a telephone interview. Injections may only have to be given once every few months, he said. De Vivo said he is a consultant to Isis.

Roche in November said it would pay as much as $490 million for experimental drugs from PTC Therapeutics Inc. to treat spinal muscular atrophy. Novartis also has been testing drugs for the disease. Neither of these efforts have yet advanced to human tests.

Roche and Novartis are working with the Spinal Muscular Atrophy Foundation. The foundation, along with other SMA groups, has also funded a researcher at Cold Spring Harbor Laboratory, Adrian Krainer, whose work helped lead to the Isis drug.

The charity was created in 2003 by Dinakar Singh, who runs the hedge fund TPG-Axon Capital Management LP, to find a treatment for his sixth-grade daughter Arya and others with the disease. He has spent almost $100 million on the effort since then.

http://www.businessweek.com/news/2012-01-04/biogen-may-pay-as-much-as-299-million-for-isis-drug.html

El País
by Sandro Pozzi
December 26, 2011

Las cifras ayudan a entender la batalla que libran Dinakar Singh y Loren Eng, millonario y exsocio del banco Goldman Sachs, y su esposa, Loren Eng, por su hija Arya. Entre los más de 312 millones de habitantes de EE UU, solo 9.000 tiene la enfermedad infantil conocida como atrofia muscular espinal (AME). Eso significa que uno entre cada 10.000 niños que nacen están afectados por esta dolencia neuromuscular hereditaria que les debilita de forma progresiva. En los casos más graves, mueren a los pocos días de nacer.

A Arya Singh, de 11 años, le fue diagnosticada la enfermedad cuando tenía 18 meses. Ahora va al colegio en silla de ruedas. Pero es de las afortunadas, a pesar del sufrimiento y de la discapacidad, porque la mayoría de los niños con AME mueren en los primeros años de vida. Pero como dice su madre, “correr una gran carrera no sirve si te paras antes de cruzar la meta”.

Esa actitud puede marcar la diferencia entre la vida y la muerte. Lo saben otros padres ricos con niños que padecen enfermedades raras, que financian la investigación previa necesaria para el desarrollo de tratamientos. Es el caso de James Simons, de Renaissance Technologies, el segundo mayor donante a la investigación del autismo.

Son los Rockefeller del siglo XXI, en referencia al primer gran filántropo de EE UU. Una lista cada vez más grande de personas con fortuna que, como el inversor Alexander Silver, de P2 Capital, se movilizan por sus hijos. O Paul Joseph, de Morgan Stanley. Se trata de abordar problemas y buscar soluciones que sirvan también para otros niños.

A pesar de la crisis, los 50 mayores donantes de fondos en EE UU comprometieron, en 2010, un total de 2.500 millones de euros a diversas causas. Entre ellos, nueve dieron más de 75 millones cada uno. En 2011 se espera un repunte en la actividad filantrópica. Son los donantes más jóvenes —menos de 50 años de edad— los que dan su dinero a proyectos relacionados con la medicina, hospitales y centros médicos.

Dado el pequeño número de potenciales clientes, la industria farmacéutica no corre el riesgo de dirigir grandes cantidades de recursos a investigar y dar con un tratamiento para estas enfermedades raras. Ahí es justamente donde actúa la fundación SMA, creada hace ocho años por de este antiguo socio de Goldman Sachs y su esposa. Otras fundaciones se orientan a facilitar el día a día de la enfermedad.

Como en la esclerosis lateral amiotrófica (ELA), en la atrofia muscular espinal los músculos se debilitan dejando las mentes de sus víctimas atrapadas en sus cuerpos. Se trata de un grupo de enfermedades hereditarias que provocan degeneración y debilidad muscular progresiva, que finalmente llevan a la muerte, según los Institutos Nacionales de Salud (EE UU). En España nacen 100 casos nuevos por año y se considera que hay más de 1.500 familias con afectados, según la Fundación Atrofia Muscular Espinal.

Lo que hace la AME diferente de otras enfermedades es que con una “estrategia inteligente” se pueden lograr grandes avances, y eso significa que existe la esperanza de desarrollar un fármaco para el que está considerado como el mayor asesino genético de bebés y niños en EE UU.

Hace cinco años, la AME llevó su lucha al Senado, buscando apoyo, porque las farmacéuticas solo se interesan en una fase ya muy avanzada en la investigación, cuando perciben que el riesgo es menor. En las enfermedades infantiles raras el avance supone, señalan desde la fundación, todo un reto a la hora de traducirlo en soluciones reales. Singh y Enn quieren acelerar el proceso, movilizando los fondos que necesitan los científicos y atraer a las farmacéuticas.

Singh sabe de números. Su firma, TPG-Axon Capital, maneja activos por valor de 7.500 millones de euros. Es uno de los grandes jugadores del negocio especulativo. En 2004 rompió lazos con Goldman Sachs. Se calcula lleva invertidos 76 millones de su bolsillo a combatir la AME.

La causa de la enfermedad está en un defecto en el gen SMN1. Hay unos seis millones de estadounidenses portadores, es decir, una de cada 50 personas, y si ambos progenitores son portadores, la probabilidad de que el hijo padezca la enfermedad es de una entre cuatro, y no hay cura.

Karen Chen, miembro del comité científico de la Fundación SMA, deja claro que “Arya simboliza todo lo que queremos hacer por otros niños que sufren la enfermedad”. Como no disponen de laboratorios propios, buscan combinar el trabajo académico y de la industria. Como vicepresidenta de la SMA Foundation aparece Cynthia Joyce, que trabajó para Ciba Pharmaceuticals, ahora controlada por Novartis.

Joyce es una firme defensora de la participación de las organizaciones sin ánimo de lucro en el desarrollo de terapias. Novartis podría pasar, en dos años, de las pruebas con ratones a humanos. También colabora PTC Therapeutics, que cuenta con un tratamiento que prolonga la vida de los ratones enfermos. Y ISIS Pharmaceuticals tiene un medicamento para probar en humanos.

Los lazos de esta fundación también tocan el frente académico, colaborando con las universidades de Columbia —donde siguen la evolución de Arya—, Pensilvania y Harvard. “Nuestra estrategia, como están empezando a hacer otras fundaciones, es implicarnos de lleno en la investigación. No esperar a los resultados”, precisa Eng. Arya sabe de su enfermedad y de los sacrificios que conlleva para ella y su familia. La intención es que participe en los ensayos clínicos.