FDA and Rare Disease Drug Development, from FDA Week

June 29, 2010 // [FDA Week, http://insidehealthpolicy.com/]

FDA is currently in the middle of a flurry of activity aimed at better focusing its regulation of rare disease treatments, but the agency disappointed some outside advocates by delaying the possibility of creating a special rare disease review division within FDA for at least a year. That news came to advocates from FDA staffers an hour before a Senate Appropriations subcommittee looking at federal regulation of these diseases last Wednesday (June 23), a source said. More surprising to the source were comments from National Organization for Rare Disorders leadership during the hearing that the establishment of the new agency division would be a mistake.

FDA has two working groups addressing the issue and a number of rare disease regulatory advocates are proposing improvements to the agency’s regulatory regime. Senate appropriators are also eying whether legislation is needed.

The concept of a rare disease review division has been championed by the Emil Kakkis and his foundation, which has long advocated for Congress to provide FDA $10 million to create the special division. Kakkis and other rare-disease treatment advocates argue that gathering FDA’s experts in the field into one group would help accelerate the regulatory process.

The move would have an “immediate impact on new treatments” and would signal to the biotechnology industry that the agency was “serious” about this effort, Kakkis told the Senate FDA appropriations subcommittee. A special division would encourage more investment and allow for products already in the pipeline to be more quickly acted on, Kakkis said.

FDA should “have a division that has particularly trained people in the diseases that are both chemical, muscular or some of the other genetic rare disorders that take specialized expertise,” Kakkis told the subcommittee. The best regulation would come from consolidating FDA’s experts who are “scattered throughout” the agency, adding staff and building a division where staffers can avoid “having their expertise diffused and not leveraged over time,” Kakkis said.

The problem without a dedicated division also comes with a lack of centralized responsibility for reviewers, Kakkis added. “There are definitely people [in FDA] with expertise who can review these, but often they are called on to do other tasks,” Kakkis said. “This is a way to get better decision-making.”

But a Kakkis foundation staffer told FDA Week that meetings between advocates and FDA staffers prior to the hearing indicated that, while conceptually supportive of the idea of specialization, the timing did not work for the division to be created this year. That impression became formal an hour before the hearing.

The source said his reading of the situation was that FDA was possibly waiting until after drug user fees are reauthorized in 2012 to create the office.

The “biggest shock” from the day, the source said, came from Diane Dorman, the National Organization for Rare Disorders’ vice president for public policy, who said NORD flat-out disagreed with the concept. Dorman said NORD was “somewhat concerned” because of the worry that a separate division would create “narrow silos” within FDA.

By way of example, Dorman described the National Institutes of Health’s office on rare diseases as a nimble group with which the office’s director can leverage opportunities across all NIH offices and institutes without barriers. There’s a possibility to create an ad hoc group, “but creating an additional silo [within FDA] in our opinion may cause problems to access,” Dorman told the subcommittee.

In his response, Kakkis said without the review division FDA “cannot alter the review process for drugs in a way that is fundamental.” Creation of the division would let staffers be “personally responsible to make decisions,” he added.

“I think you’d want your drugs to be reviewed by people who are trained in the area, that specialized in it, and really understand it,” Kakkis said.

FDA Deputy Commissioner for Science and Public Health Jesse Goodman said the agency is aggressively addressing orphan drug issues, pointing to two new expert working groups FDA established in March, the Rare Disease Review Group and the Neglected Disease Review Group.

Those workgroups “will look at all the ideas we’ve heard here” before issuing a report to Congress, Goodman said. The two groups were created to help implement language in the FY 2010 Appropriation Act, which directed FDA to establish the internal review groups to address rare and neglected diseases, and to report to Congress one year after establishing the groups before issuing guidance.

That language came at a request from Sen. Sam Brownback (R-KS), the ranking member on the subcommittee.

Other work recently undertaken by FDA include the agency’s Office of Orphan Products Development starting use of a new tool, the Rare Disease Repurposing Database, which identifies drugs deemed promising for rare illnesses and are already approved by FDA for another disease (see related story).

A “novel feature and major advantage of this database” is its focus on drugs that have already gone through the FDA approval process, Goodman noted in its written testimony. “Thus, repurposing of these drugs for a new rare disease indication might be attainable quickly, relatively inexpensively, and at great benefit to the patients involved.”

In February, FDA created a position of associate director for rare diseases in the Center for Drug Evaluation and Research, which serves as the center’s focal point to the orphan drug development community “in navigating the complex regulatory requirements for bringing safe and effective treatments to patients,” Goodman wrote.

The agency is also collaborating with other entities to help ramp up its rare-disease treatment efforts.

In October 2010, FDA will co-sponsor its first rare disease investigator training course, in collaboration with NORD and NIH. FDA is also planning a series of scientific workshops to address difficult rare disease research issues. And FDA and NIH are co-sponsoring an Institute of Medicine study to review national policy for rare disease research and related medical product regulation, with recommendations due this September.

Experts suggest that there are roughly 200 FDA-approved treatments for the nearly 7,000 rare diseases that exist globally. So “while there have been many successes, the unmet needs are huge,” Goodman told the subcommittee. Rare diseases are defined as diseases affecting fewer than 200,000 people in the United States.

The FDA estimates that a billion people worldwide are affected by at least one neglected disease like tuberculosis, malaria and leprosy.

These issues are FDA’s concern because “infectious diseases know no boundaries,” Goodman said. “Threats to health anywhere are threats to everyone.”

The agency also is preparing for public hearings on June 29-30 focusing on how it approves and encourages medical products for rare diseases. — Seth Freedland (sfreedland@iwpnews.com)

Children’s Rare Disease Network Partners With Medpedia.com To Create Rarespace

Online Knowledge Share Platform to Provide Valuable Information to Rare Disease Community

Dana Point, Calif. (June 29, 2010) – Every parent needs a supportive, collaborative network full of information where medical professionals, researchers, patients, parents, advocates and the general public share knowledge about the rare childhood diseases that affect 22.5 million American families. RareSpace is an online knowledge sharing platform designed in partnership with R.A.R.E. Project, the Children’s Rare Disease Network and Medpedia.com to help grow resources for children with special needs. This resource is available online now at RareSpace.

“RareSpace is a unique and valuable tool for families caring for children with rare diseases,” says Jonathan Jacoby, CEO of the R.A.R.E Project. “With the help of Medpedia.com, RareSpace will become a safe place to share important information aggregated from the rare disease community at large, which is vital to finding hope for children.”

It’s the collaborative structure of RareSpace that makes it truly unique. The site will educate and connect users about critical resources, innovations in research, standards of care as well as best practices in treating rare diseases and disorders. Creating a community filled with medical professionals, policy advocates, researchers and parents catalyzes a free exchange of information, increasing the general knowledge quotient of every stakeholder. The goal is to supply real resources and connections for those who are in the care of children living with rare diseases and disorders, and help each family not feel isolated in their struggles to care, treat and advocate for these sick children.

“It’s so critical for families and caregivers to have a knowledge bank like RareSpace to draw from,” says Devon Watts, community manager at Medpedia.com. “We are excited that Medpedia.com is a part of connecting a community and granting an open space for dialogue and education. It’s the widespread sharing of information that will benefit patients most.”

Different from other community sites, one key advantage of RareSpace is that people can share documents and resources very easily. Discussions of genetics and genetic diseases in general happen on RareSpace, with the understanding that research on all these diseases could lead to cures for other genetic disorders as well. Articles on translational research and discussions of possible cures for diseases can be found on RareSpace. A major benefit is that medical professionals will answer questions posed by site users about treatment, best practices and how to best help these children and their families. Users will create profiles and have the opportunity to upload documents and links and connect with other users all within the RareSpace portal. In addition to connecting within RareSpace, users will have the ability to create disease specific groups that can all be linked with RareSpace. This robust platform provides numerous ways to share critical information and knowledge across the rare disease community, which can be done in a safe environment that includes representation from all of the key stakeholders involved in rare disease.

R.A.R.E. Project’s, Jonathan Jacoby to present at FDA Hearing on Rare Disease

On Tuesday, June 29, 2010, and Wednesday, June 30, 2010, FDA’s Office of Orphan Products Development will host a two-day public hearing and Webcast on the Development of Articles for Rare Diseases.

This public hearing is intended to gain from health care providers, academia, industry, patients, and other interested persons their perspectives on various aspects of the development of medical products for the diagnosis, treatment, or management of rare diseases. The input from this public hearing will help inform the work of FDA’s committee for rare diseases

Jonathan Jacoby, CEO R.A.R.E Project will present case studies on therapeutic candidate generation, focusing on;

• Challenges of patient-driven R&D
• Challenges and successes with biomarker identification
• Experience with Orphan Drug Designations
• Individual investigator INDs and IND exemptions
• NIH clinical trials
• Barriers to recruitment and participation in CTs

Following the presentation, Jacoby will provide recommendations that include the importance of very small CTs as a pathway to regulatory approval. Jacoby will present this testimony from 11:40 – 12:00, June 29, 2010.

The meeting will be webcasted and any interested persons are encouraged to join:

• Dates: June 29-30, 2010
• Time: 9:00 AM to 5:00 PM ET
• Webcast addresses (will be active at the time of webcast):
  June 29 – collaboration.fda.gov
  June 30 – collaboration.fda.gov

Tips to help your doctor put the “Missing Clues” together by Dr. Geeta Nayyar

This is my first post on the R.A.R.E. Blog and I would like to say how honored I am to have been invited to be a contributor. I really admire the mission of this network and hope that I can be valuable in some small way.

As a Rheumatologist, who sees patients with rare diseases I understand firsthand the trials and tribulations that many patients and families go through when dealing with a rare disease. It is hard enough to be sick and even harder still when confusion may surround a diagnosis or treatment plan. Often it can feel like “no one understands, not even your doctor.”

Rare diseases are often hard to diagnose, and even harder to treat and manage. Families will often have to see not just one doctor, but many doctors and specialists throughout a lifetime. This can be burdensome and cumbersome not only for patients and families but also for your doctor to manage.

I would like to provide the readers today with some tips and insights for a smoother doctor’s visit especially when seeing a physician for the first time or for a second opinion.

Being a physician is a little bit like being a detective. A doctor relies on good information and medical data as the “clues” to solving a “mystery” (the diagnosis). Part of the key to solving any “mystery” is good fact finding and data collected in a timely manner.

The health care system today can make this process very difficult. Data can be hard to keep track of when going from doctor to doctor or institution to institution. Medical records can be lost or incomplete, or can even be delayed when transferring between hospitals.

One of the best things any patient advocate can do to take care of their loved one, is to help their doctors organize the “clues” in the “case.”

A physician uses a variety of tools and “clues” when trying to put together a diagnosis and treatment plan for a patient. These “clues” come from a variety of sources. They can take the form of: lab work, radiology images, biopsy reports, medical history, physical exam findings and inputs from other clinicians or specialists.

I can’t tell you how many times patients come to me and stare at me blankly when I ask for their old medical records. They somehow think I can “just look in my computer” and it will all be there… I wish it was that simple.

If their prior “detective work” was done by a different doctor not affiliated with my hospital I have absolutely no record of that information and essentially must start my “detective work” from scratch. This can often mean repeating unnecessary blood work or radiology images or even still…a loss of time for that patient or family in reaching their diagnosis and treatment.

While the country is making strides towards improving the sharing of health data and information by encouraging the adoption of electronic medical records, we still have a lot to do and all of this will take time. The HITECH Act of 2009 is a step in the right direction. This policy will authorize billions of dollars of reimbursement incentives to health care providers who can demonstrate “meaningful use” of electronic health records.

However, in the mean time, I encourage all patients and families to take charge and control of their personal medical information and to share this with their provider. Your doctor will be happy you did and it will make their job, of solving the “mystery” (diagnosis) much easier.

For those of you who are comfortable with technology, I encourage you to look into a variety of personal health records on the market today that can help make managing what seems like mounds of medical paperwork into a few simple electronic files that can be managed with a few clicks. If you are not comfortable with technology, I encourage you to keep diligent paper files that are organized by categories. (For example by: lab work, radiology, pathology etc…) I also urge you to make copies and have back up files available either via paper or scanned electronically. Additionally, should you travel, make sure you pack your records or have access to your records remotely in the event of an emergency.

All of the above can make an already daunting process much simpler for both you and your doctor. Remember that practicing medicine is a little bit like solving a mystery, and doing so with “missing clues” or medical information makes it that much harder. The more you can take control and help your doctor with “clues” and fact finding the more you will accomplish together.

FDA Database Aims to Spark Orphan-Disease Drug Development

By Amy Dockser Marcus

For months now, the Food and Drug Administration has been trying novel ways of encouraging drug makers to develop drugs for rare diseases.
Today the agency’s Office of Orphan Products Development is launching a new gambit—a database of FDA-approved compounds and products that show promise in rare diseases too.

The concept is called “repurposing” — finding new ways to use products that have already been okayed by the FDA for some other use.

The already-approved products in the Rare Disease Repurposing Database are unique in that they’ve also previously received orphan-drug designation, meaning they’ve shown potential to treat one or more of the diseases affecting 200,000 or fewer Americans. (While orphan-drug status doesn’t guarantee FDA approval as a treatment for the rare disease, it’s a prerequisite for getting incentives such as tax breaks and marketing exclusivity if the agency does okay the drug for that purpose.)

Timothy Coté, director of the orphan products development office, says that testing an already-approved drug as a treatment for a rare disease has significant advantages — for one, it’s already been found safe by the FDA. And running trials on an existing drug is much cheaper than trying to develop a totally new compound.

Despite the incentives in the Orphan Drug Act, there are only about 350 such drugs that have been approved — and there are some 7,000 rare diseases.

Information in the database is already publicly available through the FDA but until now has been scattered. Coté says officials went through more than 2,000 orphan drug designations to compile the new 235-drug database, which he says is likely to be used not only by drug companies but also by venture capitalists looking for promising investments and patient advocacy groups eager to drive drug development for their rare condition.

Coté says he hopes the new database will spark drug development efforts. But he plans to do some repurposing of his own. He says the next step after the database is released is for his office to carefully study the list, identify some particularly promising products, and urge the companies to move forward.

Link to article

Why Rare Disease Research Matters, by Leslie Gordon

The Progeria Research Foundation (PRF) was formed 11 years ago to find the cause, treatment, and cure for Progeria.  Progeria is a rare, fatal genetic condition characterized by an appearance of accelerated aging in children.  All children with Progeria die of heart attack or stroke by an average age of 13 years.  In 2003, the genetic mutation that causes Progeria was discovered on the Lamin A gene.

Progeria is one of the rarest known diseases. With a reported incidence of about one in 4-8 million newborns, there are only 65 known children currently living with Progeria worldwide.  When my son Sam was diagnosed 12 years ago, we turned to research and literature for more information.  There was nothing, and so, with my husband, sister, friends, colleagues, and other family members, we formed PRF to help drive research. 

Over the last 10 years, PRF has made significant strides impacting policy (PRF was instrumental in securing language in the Children’s Health Act of 2000 that mandates the National Institutes of Health to report on its plan for supporting children with Progeria); establishing research partnerships (The PRF Genetics Consortium identified the gene that causes Progeria less than 10 months after its formation in 2002); and driving the search for potential treatments and a cure (clinical trials for potential treatments are underway). 

The research over the last several years has helped us uncover a tremendous amount about Progeria and progerin, the protein caused by the genetic mutation.  At the same time, this research may help us better understand heart disease, the number one cause of death in the United States, as well as the process of aging.  As it turns out, we all produce a little bit of progerin, and the amount of progerin in our bodies increases with age.  But how much progerin does each person have and how does it differ among patient sub-populations?  Understanding more about Lamin A and progerin could lead to insights and treatments for patient sub-populations suffering from cardiovascular disease. 

That, to me, is exactly why scientific research in rare diseases is so important.  When we started our research in Progeria, we had no idea that the investigation of a disease that impacts a few children could potentially impact many. 

Now PRF is funding clinical trials and studying multiple treatment possibilities for Progeria, while continuing to examine the similarities between children with Progeria and people experiencing “normal” aging and heart disease.  I look forward to sharing the results of those studies with you in the coming months, and to continuing research that will benefit children with Progeria, as well as other sub-sets of patients. 

Stay tuned to The Age of Personalized Medicine Blog next week for an update from Audrey Gordon, the executive director of PRF, on exciting developments discussed at our recent scientific workshop, and the collaborations that have helped to advance research in Progeria from bench to bedside.

Leslie Gordon is Medical Director of the Progeria Research Foundation

// Cross Posted from Personalized Medicine Coalition’s Age of Personalized Medicine Blog (APM website here).

How ‘Brain Training’ Can Make You Smarter

As many people hit mid-life they often start to notice that their memory and mental clarity are not what they used to be. As the brain fades, we euphemistically refer to these occurrences as “senior moments”.

While seemingly innocent, this loss of mental focus can potentially have a detrimental impact on our professional, social, and personal wellbeing.

It happens to most of us, but is it inevitable?

From HowLifeWorks.com:

Neuroscientists are increasingly showing that there’s actually a lot that can be done. It turns that the brain needs exercise in much the same way our muscles do, and the right mental workouts can significantly improve our basic cognitive functions. Thinking is essentially a process of making neural connections in the brain.

Now, a new San Francisco web-based company has taken it a step further and developed the first “brain training program” designed to actually help people improve and regain their mental sharpness. Called Lumosity, it was designed by some of the leading experts in neuroscience and cognitive psychology from Stanford University.

Lumosity, is far more than an online place to exercise your mental skills. That’s because they have integrated these exercises into a web-based program that allows you to systematically improve your memory and attention skills. The program keeps track of your progress and provides detailed feedback on your performance and improvement.

In randomized, controlled clinical trials Lumosity was shown to significantly improve basic cognitive functions. One study showed students improved their scores on math tests by 34% after using Lumosity for 6 weeks, significantly greater gains than those made by other students in the same class, who were not training with the Lumosity program.

The company says its users have reported clearer and quicker thinking, improved memory for names, numbers, directions, etc., increased alertness and awareness, elevated mood and better concentration at work or while driving.

>> FULL STORY – ALSO LUMINOSITY.COM

Welcome to Scientific Curiosity.

I never expected for my very first question to get picked for an answer (see first question here), and then last Friday I was so excited to see my twitter question featured on the Office of Science and Technology Blog, “Who Do You Credit For Your Scientific Interests?” I feel almost famous and delightfully nerdy (the White House OSTP Blog, White House). This week, I tweeted a question for Billy (this really is the sort of thing he likes to wonder about).

To ask a burning question of Dr. Holdren, send an e-mail to AskDrH@ostp.gov or tweet your short question to @whitehouseostpwith hashtag #AskDrH. Dr. Holdren will select one query each week and answer it via a short blog post to appear every Friday.

Orphan Drugs Rare Disease Opportunity, Investors Eye

Investors are warming up to the economics of rare disease orphan drugs as potentially big moneymakers.  As much as we love to bash Wall Street, the financial sector has found gold in orphan drugs for treating rare disease, and that might just fill in a deficit of research capital, which would otherwise be unavailable where and when its needed for orphan disease and disorder treatment drugs.

From The Motley Fool | 5/25/10 :

Orphan drugs don’t have the potential patient numbers that cholesterol or diabetes drugs have, but that doesn’t mean you should ignore them either.  What they lack in volume they make up for in price.

Technically speaking, a drug can get orphan drug status if it treats a disease that affects less than 200,000 people in the U.S. A lot of cancers fall into that range — for instance, GlaxoSmithKline’s (NYSE: GSK) Tykerb has orphan drug status for gastric cancer. But the true orphan drugs treat diseases you’ve probably never have heard of.

A little protection goes a long way

There really are some financial incentives to gaining rare disease orphan drug treatment status. The government kicks back up to 50% of the cost of clinical trials in the form of tax credits. And the Food and Drug Administration comps the fee established by the Prescription Drug User Fee Act (PDUFA) that drugmakers pay when submitting their orphan disease marketing application.

But the biggest advantage comes from the exclusive sales of the rare disease orphan drug treatment for seven years in the U.S. and six to 10 years in the EU that governments give orphan drugs. It doesn’t matter whether patents expire during that time, the regulatory agencies will hold off approving generic competition until the rare disease orphan drug treatment exclusivity has expired.

The Motley Fool:

Being the first to treat a disease also offers an indirect lockup of patients from other branded drugs. If the drug works well enough, patients are less likely to enter a clinical trial for a competitor’s experimental drug, making it harder for the competitor to get on the market. Being first doesn’t provide an absolute monopoly — in addition to Genzyme’s (Nasdaq: GENZ) Cerezyme, Shire’s Vpriv is approved for Gaucher disease and Protalix and Pfizer (NYSE: PFE) are also working on a Gaucher disease treatment — but a little protection can go a long way.

On the road to bigger things

Sometimes the orphan disease drug status is just a starting point. Because the proteins that drugs interact with are often involved with other diseases, treating an orphan disease can be a good starting point before launching into another disease that may not be so rare.

READ THE COMPLETE ARTICLE AT MOTLEY FOOL

Emergencies: Are You Prepared?

Depending on the specific rare disease your family faces, having the right kind of emergency care can mean the difference in life or death.  In my family we’re dealing with a connective tissue disorder called Vascular Ehlers-Danlos Syndrome (VEDS) and because patients can look and act perfectly normal — and might even have “normal” vital signs,  EMT’s  can easily mistake serious symptoms for benign problems. 

Even in children, abdominal pain or jaw pain can be the only signal to a serious arterial complication such as an aneurysm or dissection.  Cramping and constipation might mean that their intestine has ruptured.   Often times, if it’s a “slow bleed”, their vital signs will be normal enough – and because situations like these are “unheard of in children”, the REAL diagnosis is missed, treatment is delayed, and lives are lost.  The night before I lost my husband his BP and heart rate were “normal” when the paramedics arrived; they even had him walk down a flight of stairs to get on the gurney himself (despite the pleas of his frantically screaming wife).   Within an hour of getting to the hospital, the CT had shown that his abdominal aorta had ruptured and was bleeding into surrounding tissue.  Unfortunately, there was nothing anyone could have done to save my husband; his tissue was too fragile and the outcome was unavoidable.    However, for many patients with VEDS and similar disorders, time is critical – and proper management CAN save their lives. 

One of my greatest fears in raising my son, is that if or when an emergency arises for HIM, we’ll be faced with paramedics who are trying to safe his life, but again have no idea what they’re dealing with. 

Even with a medical alert bracelet, I’m well aware that most emergency personnel have probably never heard of his disease – much less know what to do for my son in a crisis. 

To be honest, that fear has haunted me for all of the 13 years since losing my husband.  There are too many stories of families who’ve gone through very similar situations, and in their cases their loved ones could have been saved.  I’ve struggled with the reality that (through no fault of their own) I know more about my son’s disease than the emergency personnel do.

Then, a couple of months ago, I stumbled onto some information that somewhat eased  those fears for me.  I was talking with a fireman who’d come to the school where I work to do safety presentations with the students.  During our conversation, I found out that I can call our local 911 director and list all of my son’s medical information including the “Do’s” and “Don’ts” for emergency care. 

With this information on record, if a call ever comes into 911 from any of the phone numbers I give them – or if a call comes in with my son’s name in it – no matter which agency responds, they’ll have the same info.  I can list what hospitals to take him to and which doctors to contact for instructions.  All of which is a HUGE relief because I know (from experience) that the whole “frantic-screaming-panicky mom” thing doesn’t work all that well. 

VEDS isn’t the only disorder, syndrome, or disease that requires specific emergency care.   Many other connective tissue disorders such as Marfan Syndrome, Loeys-Dietz Syndrome, and Turner Syndrome also produce deadly but invisible vascular complications.  I’m also very sure there are countless other rare diseases that first responders won’t know much about but for which those first few moments of care can be so critical – which is why I decided to write about it. 

The contact information may be a little different in each area or county, but if you start by calling your local fire department, police or sheriff’s department, they can probably put you on the right track.  There may even be an actual listing in the yellow pages (do people still use yellow pages?). 

If you’re anything like me, trying to anticipate the endless scenarios your child could encounter takes up a lot of your time whether you mean for it to or not.  And yes, I know there’s no real way to be prepared for every possible emergency or crisis, but it doesn’t mean I’ll stop trying.   Hopefully, knowing that services like these are available will help ease some of that worry just a little bit.  

BTW — I would really like to hear from any readers who have other great ideas or suggestions for emergency plans/preparations – regardless of the specific disease!

For more information about Ehlers-Danlos Syndrome, please visit:

Ehlers-Danlos Network C.A.R.E.S.  at   www.ehlersdanlosnetwork.org

For information on genetic diseases that cause aortic aneurysm/dissection in adults & children:

TAD Coalition (Thoracic Aortic Disease)  -  www.tadcoalition.org

The John Ritter Foundation for Aortic Health - www.johnritterfoundation.org

 

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