FDA and EMA Forge Rare Disease Collaboration; Announcement Coincides with World Rare Disease Day 2010

In recognition of World Rare Disease Day 2010, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) announced that they will collaborate together and now accept a single annual report from sponsors with an orphan drug designation for rare medical conditions.

The joint announcement was made by Dr. Timothy Cote, director of FDA’s Office of Orphan Products Development and Dr. Jordi Llinares, head of Orphan Medicines at the EMA and marks an important step forward towards increasing data sharing between the two agencies.

An ‘annual report’ for an orphan drug is information that is typically provided about the development of orphan medical products, including a review and status of ongoing clinical studies, a description of the investigation plan and anticipated or current problems in the process that may impact an orphan product designation.

The submission is voluntary and applies only to sponsors who have obtained an orphan designation status for their product from both the FDA and EMA. Each regulatory body will conduct their own review and assessment of the annual report to assure the information meets all the legal and scientific requirements of each agency.

By allowing a single annual report submission to both regulatory agencies, the paperwork process is streamlined and precious time is saved as organizations can focus their energies on moving drug development forward instead of duplicating paperwork efforts. The FDA and EMA plan to exchange the annual reports electronically through a secure portal starting Feb. 28, 2010.

Hopefully, we will see more of this type of collaboration in the future by both agencies.  I am looking into filing my Orphan Drug Application for Cyclodextrin with the EMA and I am happy to see the two agencies working more closely together.

FDA Orphan Drug Workshop Makes Filing Applications Easy – Even For Rare Disease Patient Advocates!

At a historic orphan drug workshop held by the U.S. Food and Drug Administration Feb. 25-26 and before World Rare Disease Day 2010, we filed a momentous orphan drug application with the FDA for the treatment of Niemann Pick Type C disease with cyclodextrin. Our filing occurred in Claremont, CA, at the Keck Graduate Institute’s Center for Rare Disease Therapies, at 4pm on Friday in the Founder’s Room.

Typically rare disease drug applications are filed by pharmaceutical or biotech companies but our application was filed as patient advocates on behalf of the entire Niemann Pick Type C disease community worldwide. Children’s Hospital of Oakland Research Institute (CHORI) and Dr. Caroline Hastings, Addi and Cassi’s physician, are the official sponsors of the application.

Over the two day FDA workshop, Dr. Ron Browne (a medical consultant hired to helped compile the application over the past few months) and I met with FDA officials. We had four 30 minute meetings over two days to get advice on our filing and make sure we were following all proper procedures to give us the best chance at obtaining an orphan status designation for cyclodextrin. For those considering attending the FDA Orphan Drug Workshop, I would highly recommend it! The next one will be held at the University of Minnesota August 3-4, 2010.

We filled two binders (one original and one copy) with information on Hydroxy Propel Beta Cyclodextrin (HPBCD) for the treatment of Niemann Pick Type C Disease. Niemann Pick Type C disease is a very rare, relentlessly progressive and eventually fatal neurodegenerative genetic cholesterol disorder that afflicts my six year old twins. We made our official submission in hot pink binders (probably a first for the FDA!) as pink is Addi and Cassi’s favorite color.

Approximately 15 other organizations attending the FDA orphan drug workshop filed applications for new rare disease drugs or biologics. We all now wait 60 days to see if the FDAs review division grants us official orphan drug designations.

I learned at the FDA workshop that approximately 60-70% of the orphan drug applications submitted to the FDA result in the granting of orphan status.  The two main criteria that must be met to receive a designation as an orphan drug are:

1.    Prevalence (less than 200,000 in the US are affected with the rare disease/condition)
2.    Promise (there is a medical rationale for believing that a proposed drug has “promise” for treating the rare disease/condition)

With NPC disease and Cyclodextrin, I believe we easily meet both criteria and we are optimistic that will get a designation.

Only one other orphan drug application in history has been filed with the FDA to treat Niemann Pick Type C disease.  This application was made by a Swiss pharmaceutical company called Actelion Corporation for a drug called Zavesca (Miglustat). Zavesca is currently under review and the FDA will make a decision in early March as to whether it approves Zavesca for the treatment of Niemann Pick Type C disease.

Based upon recent animal studies, Cyclodextrin appears to have far greater promise for the treatment of NPC disease than Zavesca.  The goal of this filing to to move forward with the research in order to verify efficacy and to give kids with Niemann Pick Type C disease a real chance at life.

A True Healthcare Reform Idea – Priority Review Vouchers For Ultra Rare Diseases

This week I have been reading all about priority review vouchers. Henry Grabowski and other faculty at Duke University came up with the idea for providing an incentive for drugmakers to target certain tropical and infectious diseases (such as TB, malaria, cholera, dengue, leprosy) affecting poor nations.  Senators Sam Brownback (R-KS) and Sherrod Brown (D-OH) sponsored this and the idea went from a proposal to being enacted as U.S. law in 18 months!

According to the FDA, “while diseases addressed by this legislation represent an important disease burden for humanity, there has been remarkably little progress over the past 50 years in development of drugs for these diseases. Because these diseases are found primarily in poor and developing countries, existing incentives have been insufficient to encourage development of new and innovative drug therapies.”

This is similar to what is happening in the ultra rare disease category – very little progress for millions of people with chronic and life threatening diseases. And this is happening in our own country! I wonder if a similar bill with novel incentives could be implemented for ultra rare genetic diseases like Niemann Pick Type C disease where there is no significant market or financial incentive for pharmaceutical or biotech companies to invest.  Or could this bill be expanded to include Ultra Rare Diseases?

Common Rare Diseases versus Ultra Rare Diseases

When I say ultra rare diseases, I am not talking about rare diseases like Cystic Fibrosis. No offense to folks in the Cystic Fibrosis community but CF is a more common rare disease with about 30,000 patients in the US.  Over the years, there has been significant drug development for this rare disease. I am talking about unknown and obscure genetic diseases such as Niemann Pick Type C, a fatal cholesterol disorder that is often called the “childhood Alzheimer’s.”  Last I checked, there were approximately 150 living patients in US with NPC (including my six year old identical twins, Addi and Cassi).

Over the past month, I have been researching global rare disease statistics and contacting experts. I want to know one simple fact.  How many people in the United States fall into the ultra rare disease category (defined by me as 1,000 patients or less per disease type).  I pick 1,000 patients because I am fairly certain that a drug company would not pursue drug development for these small patient populations. Currently, no one can answer my question except to say, “hundreds of thousands of people” but the number could be a million or more out of the 30 million people in the US affected with over 7000 different types of rare diseases.

Rare Disease Class System Exists

Just as there are social classes, I am finding that “classes” of rare diseases exist. Despite the success of the Orphan Drug Act of 1983, Niemann Pick Type C falls into the powerless class. We are true orphans lost in a dysfunctional drug development system facing a virtually impossible and hopeless situation.

The personal hurdles I have been crossing as we move towards filing an Orphan Drug Application for Niemann Pick Type C (NPC) are tall. I must admit that the hurdles – bureaucratic red tape, research and foundation politics, lack of funding from a small patient population and zero drug development experience – at times seem insurmountable.  Between hand feeding my girls and seizure attacks, there are days when I completely break down into tears.

Stimulating Drug Development for Ultra Rare Diseases

I am looking forward to meeting Dr. Timothy Cote, Director of the FDAs Orphan Products Office, at the Orphan Drug Workshop next week at the Keck Graduate Institute. While the government’s TRND program is well intending it is time that we attempt to stimulate new drug development for ultra rare diseases in the private sector as well. I believe for any real change to happen we need novel incentives to entice companies to invest in ultra rare diseases similar to the novel incentives laid out by Grabowski and team at Duke for tropical diseases.

Ultra Rare Diseases Will Solve The Most Common Diseases

Ultra rare genetic diseases like Niemann Pick Type C disease can help scientists solve the most common diseases affecting millions of people.  Just as investment into tropical diseases can have a profound impact on global healthcare, so will the investment in ultra rare genetic diseases.

Children like Addi and Cassi can be part of the many faces behind true healthcare reform.

Numbers Don’t Add Up – Only 347 New Drugs Approved By FDA For 30 Million Americans With Rare Disease in Past 25 Years?

When it comes to finding Rare Disease statistics, the same old statistics and facts keep popping up again and again. I realize data is difficult to gather on 7000 different rare diseases that afflict 30 million Americans but it’s frustrating that sports teams and Wall Street have more comprehensive statistics when millions of people across America are chronically sick or dying.

Here are some of the alarming and scary statistics on Rare Disease I have gathered (I could not help but annotate in quotes):

• An estimated 30 million people in the United States have a rare disease and countless others worldwide.  (If you run the numbers, this works out to approximately 1 in 10 people or 10% of the US population!  Given that most of these people suffer from chronic and life threatening illnesses can you say major healthcare crisis?)
• Approximately 15 million Americans have rare diseases for which there still is no approved treatment and no research in progress.   (What????????)
• In the United States, a rare disease (also called an orphan disease) is a disease or condition affecting fewer than 200,000 persons (or about 1 per 1,000)
• According to the National Institutes of Health (NIH) there are nearly 7,000 different rare diseases (yet collectively “rare” disease is not so “rare”)
• Approximately 80% of rare diseases are attributed to genetic defects.  However, rare diseases may also occur as a result of bacterial or viral infections
• In the 25 years since the Orphan Drug Act of 1983 was signed into federal law, the FDA has (only) approved 344 treatments for rare disease.  Over 2100 orphan drug applications were filed over the same 25 year period, working out to a (paltry) 16.4% approval
• Children represent the vast majority of those afflicted with rare disease. (I have found references that 50% and possibly up to 75% of those affected by rare diseases are children like mine)

When It Comes To Rare Disease A Lot Does Not Add Up

The “official” Niemann-Pick Type C statistic states that the fatal cholesterol disease strikes an estimated 1 in 150,000 people or approximately 6 people per 1 million. Yet there are only approximately 500 known cases of Niemann Pick Type C worldwide and 250 cases in the US. With 250 cases in US diagnosed, the number works out to be more in line with 1 person per million (of the people we can find who have it). How do you have a such a high degree of discrepancy in the incidence number for this rare disease?  Maybe there are some patients undiagnosed but the numbers don’t seem to add up.  It seems like when it comes to Rare Disease a lot does not add up.

Major Healthcare Reform For Rare Disease Needed

If I sound upset, it’s because I am.  Over the past 25 years, only 347 drug treatments exist for 30 million people suffering from 7000 different rare diseases.  You can search the database here.  People keep telling me how successful the Orphan Drug Act of 1983 has been. Does this seem like success to you? It’s not at all surprising that we are in a major healthcare crisis with no end in sight.

One major piece of Healthcare reform that needs to be addressed is Rare Disease and the drug development process. Pharmaceutical and biotech companies are NOT making drugs for millions of people suffering from rare diseases because the numbers do not add up. They can’t make any money off of most of the rare diseases that have small patient populations.

The government is trying to help  (workshops, TRND program) but we are in a flatline situation when it comes to getting drugs developed and approved for rare disease.  I am happy about the$24 million pumped into the TRND program but it’s not going to make a dent when it costs $800 Million for a pharmaceutical company to make one single drug for the FDA to approve.  Again, the numbers don’t add up.

With World Rare Disease Day 2010 at the end of February, it’s time to stop talking about statistics and numbers and start talking about solutions.  A lot of little things can add up to big change.

American Heart Association Features Addi and Cassi’s Fatal Genetic Cholesterol Disorder

Thank you to the American Heart Association for featuring Addi and Cassi Hempel’s story and increasing awareness of Niemann Pick Type C, an ultra rare and fatal cellular cholesterol disease that is trying to steal our twins away from us.

We hope that by reading our story, more people will understand the significance of the Niemann Pick Type C gene in the human body and how children with this genetic disease might someday help millions of people with cholesterol-related diseases.

A Story of Hope told by Chris Hempel: American Heart Association website

In October 2007, my husband and I received life-threatening news about our cholesterol – but our lives weren’t in danger. We learned that we were born with a defect in a critical cholesterol gene and that our precious six-year-old identical twin daughters, Addi and Cassi, inherited a double mutation – both genetic cholesterol defects.

For 18 months, I’d known something was seriously wrong and had been searching for answers. Out of nowhere, Addi and Cassi started stumbling and falling down (I later learned this is called ataxia). Then they started slurring their words (dysarthria). When they started forgetting their ABCs and nursery rhymes (dementia), the doctors started connecting the dots.

Our hearts were shattered when Addi and Cassi were diagnosed with Niemann Pick Type C disease, which was caused by the double genetic mutation. We were told that they would likely die in childhood from a progressive neurological condition caused by cholesterol accumulating in their cells, specifically their brains. There was no approved medication to treat the condition and not much we could do. We were devastated.

After a few weeks of crying jags, I decided to fight the enemy – cholesterol. I wasn’t going to spend years watching my beautiful girls wither away before my eyes. I contacted researchers, searched medical Web sites and started learning everything I could about cholesterol, genetics and the Niemann-Pick Type C gene on Chromosome 18.

In my search, I found a scientific paper that mentioned a non-toxic compound called Cyclodextrin that can extract cholesterol from cells. Research in NPC-afflicted animals was showing promise. This small glimmer of hope was all I needed.

For the past two years, I’ve been working full-time to move Cyclodextrin research forward. In April 2009, the FDA allowed our doctors to give Addi and Cassi intravenous infusions of Cyclodextrin. The twins are the first people in the United States to receive this experimental treatment. It’s too early to tell whether it will save their lives or if it might help others with cholesterol-related illnesses.

Some doctors believe Niemann-Pick Type C and Alzheimer’s could have a connection due to lipid malfunctions, while HIV-AIDS researchers have discovered that the Niemann-Pick Type C gene and cholesterol help the deadly virus replicate in infected people. Many top researchers are actively studying the Niemann Pick Type C gene, including Nobel Laureates Drs. Brown and Goldstein, who co-discovered the LDL receptor. Their work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism.

Today, about 500 people (mostly children) are living with Niemann- Pick Type C disease. What scientists learn about these children might someday help millions of people with cholesterol-related diseases.

You can support the Global Genes Project by wearing jeans on World Rare Disease Day on Feb. 28!

Also, the American Heart Association helped fund grants for research on Niemann Pick Type C disease. Donate today to help fund more research grants, or get involved with one of our many causes, like Go Red For Women, Start! Heart Walk or Power To End Stroke.

It is important to note that in 2009, the FDA approved the use of hydroxypropyl beta cyclodextrin (HPBCD) in a one time clinical trial to treat Addi and Cassi.  Their treatment is currently being monitored by the FDA. If you have cholesterol-related issues, please talk to your healthcare provider about what treatment is best for you or your loved ones.

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