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Print this pageThank you very much for inviting me to join you today. I will use my allotted time to share the perspectives of patients with a rare disease called Hereditary Angioedema, or HAE for short. A plasma derived protein called C1 inhibitor concentrate has been safely and effectively used to treat this disease in Western Europe and other parts of the world for well over a dozen years. Our patient community has nothing short of a desperate need for C1 inhibitor concentrate, and we are delighted there are companies interested in licensing this product in the United States. We are also very excited that the FDA and industry are here to discuss ways to perhaps expedite the process for making vital plasma proteins available to treat rare diseases.
HAE is a rare condition in which a genetic defect causes a deficiency in the plasma protein C1 inhibitor. Dysfunctional C1 inhibitor protein permits production of vasoactive peptides that alter vascular permeability and cause edema. Accordingly, the disease is characterized by episodic swelling of the extremities, face, bowel wall, and upper airway. While HAE attacks are often painful and debilitating because edema can affect the gastrointestinal system, attacks can also be life threatening when the airway is implicated. Indeed, studies of affected kindreds have reported mortality rates of over 30 percent, with death caused by asphyxiation due to airway closure. Tragically, Americans are still dying from HAE and the disease recently claimed the life of a 12 year old girl from Alabama who expired in her father’s arms from edema that totally obstructed her airway.
HAE is a catastrophic unmet medical need in the United States because there is no therapy available to treat an HAE attack once it begins. 17 alpha alkylated anabolic steroids are useful for HAE prophylaxis in certain adults, but data from a survey by the US HAE Association reveals that many patients continue to experience periodic acute attacks notwithstanding ongoing therapy. The utility of these agents is further limited because they are not well tolerated by women, and their use is generally contraindicated for children, some of whom, tragically, are severely affected and suffer frequent attacks. Isn’t it ironic that 300 lb NFL lineman are suspended and counseled on the extreme danger posed by relatively short courses of these drugs while our patient community is relegated to chronic use of these toxic and highly undesirable agents?
In attempt to provide the most desperate patients with relief, the HAE Association provides technical assistance for patients wishing to purchase C1 inhibitor concentrate under the aegis of the FDA’s personal importation guidelines. However, C1 inhibitor is an expensive medicine, and no insurance company will provide reimbursement for an unlicensed therapy. Therefore, most of the patients who truly need C1 inhibitor therapy do not have the financial wherewithal to participate. Many of those who were able to purchase the concentrate soon realized there were limits on the number of times they could re-mortgage their homes or rely on the generosity of relatives and friends. After depleting all available resources, these brave souls are now back to living with the pain, disability, and fear of death that accompanies severe HAE.
From the patient’s point of view, the agenda for this meeting can be condensed into a two part question: How much evidence is “sufficient enough” to support licensing a plasma protein for rare diseases, and how can regulatory practice accommodate the multifaceted challenges posed by rare diseases that do not fit any standard mold? Our studies indicate that the regulatory framework for expedited licensure of medicines that benefit severely ill patients with unmet medical needs has been in place for over two decades. Indeed, the FDA’s accelerated approval regulations were first promulgated in the 1980’s by Commissioner Frank Young, and subsequently codified under the Food and Drug Modernization Act of 1997.
The HAE patient community believes that our unique situation provides an excellent vehicle for exploring the issue of expedited approval. After all, HAE is a dreadful unmet medical need, and there is compelling and longstanding evidence supporting the effectiveness and safety of C1 inhibitor concentrate. For example:
* In Western Europe, there is a sophisticated network of physician/researchers who actively treat and study HAE patients. This group of world-class experts has written hundreds of papers on HAE, and every study we have seen that discusses HAE therapy cites C1 inhibitor concentrate as the safe and effective treatment of choice for acute HAE attacks.
* The viral inactivated preparations made in Europe (and these products are the candidates for US licensure) have accumulated a remarkable safety record over the past dozen or so years. Nano-filtration is yet another viral inactivation step that will supplement patients’ and physician’s confidence in this life saving product. While safety surveillance data collection in Western Europe might not be as methodologically pure as some would like, there can be absolutely no doubt that any safety problems would have been detected and reported by the formidable group of Western European HAE experts who frequently treat their patients with C1 Inhibitor concentrate.
It is our opinion that the magnitude of cumulative safety and effectiveness evidence is sufficiently convincing, and the risks are clearly low enough, to consider
* expedited licensure of C1 inhibitor concentrate contingent upon a successful GMP inspection, with
* supplementary, but binding agreements for intensive post-marketing surveillance and other selected studies.
The impact of regulatory decisions on human life is enormous, and weighs heavy on the daily lives of many in our patient community. This is certainly the case in my family because my 20-year-old daughter suffers from extremely severe HAE, and is refractory to androgen prophylaxis. She has upwards of 20 attacks per month, and a third or more involve her airway. By dint of the insane Washington, DC metropolitan area real estate market, I am one of the fortunate who has been able to liquidate financial resources and purchase C1 inhibitor concentrate. With access to, and intelligent use of therapy, this young woman has been transformed from total disability to an honor student in finance and accounting at a local university.
Unfortunately the severity of her disease is not unusual in the HAE patient community.
Since Father’s Day is coming up again, it reminded my of the card my daughter gave me on that day last year. Her words were few, but absolutely profound, and reflect the power all of you hold in your day-to-day work: “Dad, thanks for keeping me alive.”
I will close my remarks this morning with what our patient community has dubbed, the HAE Clinical Trial Paradox. A design parameter built into a C1 inhibitor trial stipulates that patients who arrive at the clinical trial site with life threatening airway edema will not be randomized, but instead given open label C1 inhibitor therapy. Ladies and Gentleman I think that speaks for itself, and is the perfect coda for what I have shared with you today. Thank you for giving me the opportunity to speak to you this morning.
