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

February 28, 2010 by  
Filed under Featured Stories, Health Care Policy

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.

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

February 27, 2010 by  
Filed under Featured Stories

Our FDA Orphan Drug Filing For Cyclodextrin To Treat Niemann Pick Type C Disease


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.

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

February 16, 2010 by  
Filed under Featured Stories

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.

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

February 6, 2010 by  
Filed under Featured Stories

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.

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The Road to Building a New Orphan Drug – Am I Mad?

February 4, 2010 by  
Filed under Cyclodextrin

On February 25-26, 2010, I will be attending the inaugural FDA Build-an-Orphan-Drug-Workshop hosted by the Center for Rare Disease Therapies at Keck Graduate Institute (KGI) in Claremont, Calif.  FDA agency experts will be on hand to provide guidance on applying for orphan drug designation.

I will be attending the workshop with Dr. Ron Browne, hired to help us write the orphan drug application for hydroxy propel beta cyclodextrin (HPBCD).  Children’s Hospital Oakland Research Institute (CHORI) is sponsoring our orphan application as we do not have a pharmaceutical or biotechnology sponsor (a rare event in itself!). Our application is already drafted and we are attending the workshop to get final input and advice. Applications will be submitted at the close of the workshop. Perfect timing as this is the Friday before World Rare Disease Day 2010 (Feb. 28).

According to recent FDA statistics, over the past 25 years there have been 2,100 orphan designated drugs to treat rare diseases (of which 344 have become approved products). That works out to about 16.4%, which does not seem like a high percentage considering that rare conditions affect between 25-30 million Americans.  As of Feb. 8, 2010, a searchable database located on the FDA website has the number at 347/2131 which takes the percentage slightly lower.

For the most part, academics, pharmaceutical firms and biotechnology companies will be at KGI trying to find ways to move their drugs forward. Amidst all of these wonderful scientists, I (a “Mom” without a science degree) will presenting our case for a seven ring sugar molecule called cyclodextrin. Cyclodextrin has never been considered a “drug” yet this compound could save the lives of our six year old identical twins who suffer from perhaps the worst cholesterol disease on the planet.  I wonder what they are going to print on my badge?  Mom? SugarNut? More than likely “Lunatic” because I must be insane to embark on trying to get into the 16% club.

Orphan drugs are either drug or biologic products used to treat rare conditions affecting fewer than 200,000 people in the United States. Since there are only 250 children in the United States with Niemann Pick Type C disease, I think we will qualify! I am really not worried about qualifying because the science on cyclodextrin backs up our application. I am worried about how to move development forward on this compound.

I have a number of key goals:

  • Submit an exceptionally strong application for cyclodextrin
  • Determine how cyclodexrin can make it into the 16 percent club, despite the fact we only have 250 patients in US/500 Worldwide
  • Find out if the government/FDA can help us move the development of cyclodextrin forward — what kind of grants can we get for this sugar compound? Maybe some nice biotech executive with a cholesterol issue or a parent with Alzheimer’s might invest in us?
  • Determine what kind of safety and efficacy studies are reasonable for an ultra rare disease like Niemann Pick Type C.  We don’t have $800 million and 12 years to invest in moving a therapy forward when there are only a few hundred patients (many without insurance to pay for expensive drugs)
  • Understand more about animal studies that can help bolster our chances to make it into the club
  • Clarify how to move this compound forward while we are under “compassionate use” INDs with another FDA division.  How do we maximize getting data from Addi and Cassi’s treatment since they are already receiving IV cyclodextrin infusions 2x per week
  • What kind of new incentives can the government put in place for individuals like us?

By the time the two day workshop is finished, it will cost $4,000 dollars for Dr. Browne and I to attend (air, hotel, conference fee). We could really use $4,000 for an animal dosing safety study.  Every second and every penny counts when you’re trying to save your kids from a fatal childhood illness on a shoestring budget compared to the hundreds of millions of dollars of investment it takes to move a drug forward.

I hope the meeting is useful and we actually leave having filed an orphan drug application for cyclodextrin. I also hope that the FDA can learn something from a parent like me.  I may be crazy but what if I am right?

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