SUMMARY: The Food and Drug Administration (FDA or the Agency) is announcing a public hearing to obtain input on the Agency’s regulation of drugs for the treatment and/or management of amyotrophic lateral sclerosis (ALS). FDA is holding this public hearing to allow patients, caregivers, advocates, health care providers, academia, industry, and other interested persons to give their perspectives on various aspects of the development of drugs for the treatment or management of ALS. The input from this public hearing will help inform the work of FDA offices that review applications for drugs for the treatment of ALS.
DATES: Public Hearing: The public hearing will be held on February 25, 2013, from 9 a.m. to 5 p.m. However, depending on the level of public participation, the meeting may be extended or end early.
Anyone who knows what the outcome is? Jesse Raebourn was there as well!
Sentiment: Strong Buy
There are 319 interventional Phase II, Phase III and Phase IV clincial trials on "dysphagia" (difficult swallowing) over at Clinical Trials (advanced search). All INSM had to do was identify Iplex as a drug that would preserve the swallowing reflex in these ALS patients and they would be selling Iplex (or pretty near that endpoint) today. Any physician who treats ALS patients will state these patients have difficulty in swallowing, breathing and separating these two functions as the disease progresses. These same physicians will say that because of the risks of aspirating liquids, aspirating food and having difficulty in swallowing, the patients eat less, drink less and lose weight (which is converting muscle mass to blood sugar to keep the brain alive). Humans need 60 mg/decileter circulating blood sugar to remain awake. INSM could have performed a Phase IIa, IIb with preservation of swallowing reflex as the primary outcome and they would be in the final stages of getting an NDA. They did not. The result was predictable unless all the data from Italy and the EAP in the US had be exceptional data. It was not, they are not.
But lets be clear. Just what drug that is currently manufactured are you talking about for the FDA to expedite the approval of?
INSM is a strong buy because of Arikace alone and the possibilities for the liposome to function in other important types of pulmonary medicine because of macrophage uptake. Hint. Presentation of foreign substances to the immune system in the lung is mediated by fixed bronchiolar and alveolar macrophages. Hint.
Sentiment: Strong Buy
At a standing-room-only public hearing Monday, Feb. 25, 2013, people with ALS and their families, researchers, clinicians and other medical professionals urged the U.S. Food and Drug Administration (FDA) to address the unique needs of patients and their families when considering the development of therapies for amyotrophic lateral sclerosis (ALS).
More than 200 people attended the hearing, titled, "Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the Treatment of Amyotrophic Lateral Sclerosis." MDA was among the ALS patient organizations that played a significant role in prompting the FDA to conduct the first-ever hearing on ALS.
Those offering testimony included MDA President and CEO Steven M. Derks and longtime MDA research grantee Stan Appel, who is chairman of the Department of Neurology at the Methodist Neurological Institute in Houston and who directs the MDA\ALS Center at that institution. (Appel also is a member of the MDA Board of Directors and serves on its Translational Research Advisory Committee.)
Derks noted that the ALS patient and family community provides a "unique population" for FDA drug development regulation consideration.
"Patient perspectives," he said, "should be taken into account at every step of the therapy development and regulatory processes ... We are asking you to include these voices in your discussions regarding expanded access to trials, accelerated approval decisions and clinical trial design and enrollment.”
'A tremendous unmet medical need'
Appel noted that despite investments in infrastructure, natural history, basic science and clinical trials, the health outcomes for people with ALS have not changed sufficiently.
He proposed three main points, echoed by numerous other speakers throughout the day, to address the "tremendous unmet medical need" in ALS.
Prior to the initiation of efficacy trials, it may be necessary to design short, less-expensive clinical trials that can determine whether a drug can hit a therapeutic target. Such trials could help scientists more quickly determine whether a potential therapy has any chance of success in treating ALS.
Because ALS can progress rapidly, accelerated review of devices such as noninvasive ventilation and cough-assist devices is necessary to improving quality and length of life.
The symptoms of ALS — paralysis, loss of speech, loss of the ability to swallow and breathe — are in many ways equivalent to the possible side effects of experimental drugs. In other scenarios, they may be considered "intolerable," but the ALS patient community has demonstrated a willingness to tolerate significant risk. Withholding experimental therapy to prevent severe complications may be considered best practice, but a more informed risk-benefit analysis is needed for ALS.
Moving forward; overcoming regulatory barriers
Stem cell and neurobiology expert Clive Svendsen at Cedars-Sinai Medical Center in Los Angeles, urged the FDA to help research scientists speed discovery by eliminating regulations that require researchers to repeat work that has been done before. For example, it shouldn't be necessary to spend time demonstrating the safety of a particular procedure if the procedure has been determined to be safe in another trial.
Moving ahead quickly and efficiently is the goal, as noted by Svendsen and others.
"Regulatory barriers inhibit treatment, based on a traditional model that I believe should be updated," said neurologist Jonathan Glass, director of the MDA/ALS Center at Emory University School of Medicine in Atlanta. “A major impediment to developing new treatments is adherence to standardized paths that are counterproductive and do not address the complexities of this disease.”
Data sharing and the 'disease burden' of life with ALS
Other clinic team members, people with ALS and family members added their voices to the mix.
"Can we come together?" asked Mary Paolone, from the MDA/ALS Center of Hope in Philadelphia. "Can the FDA modify its policies and procedures to reflect the understanding that ALS is taking lives – human lives – at a rate that is simply unacceptable for this day and age?
Debra Quinn, who has ALS, suggested that technologies such as Skype and other forms of Web communication be considered in the introductory phases of clinical trials to help people with ALS avoid the cost and inconvenience of travel. Quinn also suggested that trial participants be allowed to continue receiving experimental therapies between trials.
Quinn's daughter Kristin shared her mother's sentiments, noting, "Today, more parents are sharing the family history of ALS with their children, and [they] understand and welcome scientific advances such as genetic testing and stem cell research.
"ALS patients have very little to lose, so I urge the FDA to give them more opportunity to leave a meaningful contribution behind."
Robert Anderson, who has ALS, was one of several speakers who addressed the FDA via prepared computer-generated speech. "We are gamblers on a big scale and any roll of the dice is better than ALS,” he said. "I ask that you join our fight as well. Give us the highest priority you can.”
For more information
Written comments about the hearing may be submitted online, through March 25, 2013, at Docket No. FDA-2013-N-0035 (click on the "Comment Now!" button), or via the United States Postal Service:
Division of Dockets Management
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
The FDA will post an archived version of the event within 45 days.
Sentiment: Strong Buy
FDA Hearing Wrap Up Part 1: Unacceptable
The February 25, 2013 FDA panel for the “Considerations Regarding Food and Drug Administration Review and Regulation of Drugs for the Treatment of Amyotrophic Lateral Sclerosis Public Hearing” heard from a vast array of speakers with information that we at ALS Connections ask the FDA to take into serious consideration as they move forward.
Suggested changes from speakers on the FDA policies and procedures included:
Creating a new model of clinical trials;
Formulating new definitions of risk, especially when targeting a disease that is 100% fatal;
Providing a fast track process for clinical trials and phases;
Determining new regulations for who can participate in clinical trials;
Learning to collaborate and share research together with (and as) organizations, clinics, and associations.
The PALS spoke as directly to the FDA, as they subtly did to the organizations who work on their behalf. More than once, it was emphasized that patients are tired of the “silos” of research.
The patient community has not only put out a call to action for the FDA to listen and develop new processes and procedures, but also are pleading with their grass roots ALS and MND non-profits to work together, share data, and “dismiss the culture of competition.”
Their lives are at stake and they want to be heard. More than that, they want to be included and involved in the many aspects of research, development, protocol, and testing.
The call is now out there for the FDA and ALS orgs to be compassionately and financially responsible to the hours of work and support ALS/MND families put toward funding efforts for research and cures; and as organizations, to truly embrace the compassionate care model the speakers urge the FDA to take; for everyone involved to think more about the death sentence PALS receive and the hope they each invest in the research they fund; and to keep in mind the devastating legacy their families endure, rather than any glory that will come in being “the one” that will find the cure.
The call from speakers went out, loud and clear, to the FDA panel that the obsolete 20th century models for accepting and approving clinical trials and drug testing no longer apply with the current 21st century advances. The also stressed that the definition of risk is different for ALS patients, who know the outcome will always be death from this disease.
Several speakers emphasized that the FDA has a responsibility to lead the changes to advance ALS treatment and that there is a need to work together with ALS organizations, which have both information and a connection to the patients they serve.
The two most common thoughts of the day came through clearly. We share the first common theme heard by speakers that much is “unacceptable” in the ALS world.
From a clinical nurse and a physical therapist who works with ALS patients, to family members, to researchers, and advocates, the resounding word heard by the panel was unacceptable. Speakers shared these thoughts with the FDA panel:
It is unacceptable that in 140 years of this disease we have no better answer to the cause of ALS/MND, no treatment options, no therapies and no effective medications.
It is unacceptable to ALS patients and researchers that the FDA remains part of the problem, rather than seeking new solutions to old models that are irrelevant and inappropriate, especially in cases of ALS.
It is unacceptable that there is only one, mostly ineffective and overpriced, drug. It is unacceptable that the $600 per month cost of this drug forces patients to choose between it and other necessary symptom-treating drugs.
It is unacceptable that the drugs which treat the symptoms PALS deal with cause other symptoms for which they need to take more drugs to combat.
It is unacceptable that we have nothing better to tell patients than they can choose either “life on a ventilator or life in hospice” until you die.
It is unacceptable that drug trials exclude ALS patients who have had the disease more than two years, or who have taken life-saving measures.
It is unacceptable that a mother must look at her child and have no answers, no cure, and no treatment options to give them. It is unacceptable to bury your child after watching 2-5 years of a debilitating disease progression.
This question was posed: Can we finally come together; can the FDA modify its policies and procedures, to understand that ALS is taking human lives at a rate that is unacceptable? As 28 year-old Peter Frates said during his speech to the FDA panel – “a 2-5 year life span is completely unacceptable.”
The only acceptable course of action by the FDA will be to make real, meaningful, and swift changes, based on the input of 60 educated and informed speakers, that will prove this hearing, as Ted Harada so frankly put it, was not a dog and pony show
Sentiment: Strong Buy