ISSUES WITH THE PRESENT FDA ON THE MATTER OF 510(k) CLEARANCE

Transcription

1 PRESENTATION TO IOM COMMITTEE ON 510(k) ISSUES WITH THE PRESENT FDA ON THE MATTER OF 510(k) CLEARANCE Robert E. Fischell, Sc. D. Founder and Chief Technology Officer Neuralieve, Inc. Washington, DC July 28,

2 PRESENTATION TO IOM COMMITTEE ON 510(K) THERE IS A GREAT CONCERN IN THE MEDICAL DEVICE INDUSTRY THAT THE FDA IS SEEKING WAYS TO DELAY AND DISRUPT THE CLEARANCE OF NEW MEDICAL DEVICES UNDER THE 510(k) REGULATIONS 2

3 PRESENTATION TO IOM COMMITTEE ON 510(K) THIS PRESENTATION IS AN EXAMPLE OF HOW THE FDA IS SLOWING THE APPROVAL OF A NEW MEDICAL DEVICE THAT CAN BRING RELIEF, WITHOUT SIDE EFFECTS, TO MILLIONS OF AMERICANS WHO SUFFER FROM MIGRAINE HEADACHES 3

4 NEURALIEVE, INC. NEURALIEVE, INC. WAS FORMED IN THE YEAR 2000 TO DEVELOP AN EXTERNAL DEVICE TO RELIEVE MIGRAINE HEADACHES WITHOUT THE USE OF DRUGS THE EXTERNAL DEVICE PRODUCES AN INTENSE MAGNETIC PULSE ONTO THE BRAIN WHICH CAUSES AN ELECTRICAL PULSE THAT CAUSES DEPOLARIZATION OF NEURONS WHICH HAS BEEN SHOWN TO DISRUPT MIGRAINE SYMPTONS THIS TREATMENT IS CALLED TRANSCRANIAL MAGNETIC STIMULATION OR TMS

5 About Transcranial Magnetic Stimulation (TMS) TMS machines have been used to study brain function for more than 30 years in tens of thousands of patients Neuralieve uses a single pulse TMS that has been cited by the NIH to be Harmless In 2008, the prior FDA cleared a Neuronetics, Inc. de novo 510(k) application to treat depression using a 50% stronger magnetic pulse compared to Neuralieve, and the Neuronetics NeuroStar device provides 30,000 to 75,000 times as many pulses per treatment as compared to the Neuralieve device In 2008 Neuralieve completed a randomized clinical study of TMS in migraine patients with aura that showed that the Neuralieve device for the treatment of migraine headache is both safe and effective

6 Effective in Treating Any Pain Pain Free Rate at 2 hours for Any Baseline Pain P = P = P = P = Full Analysis Set = ITT Full Analysis N =

7 Sustained Pain Free Rates Full Analysis Set (ITT) 2-24h 2-48h Sustained Pain Free 7

8 Symptom-Free Rates at 2 hours Significant improvement for photophobia, phonophobia and nausea P = P = P =

9 TMS Comparable Efficacy to Triptans when used after pain begins When treated during moderate / severe pain TMS 2h Pain Free Triptans 2h Pain Free P=0.019 Percent of patients 35.0% 7.4% N = Adelman, JA., Meta-analysis of oral triptan therapy JMPC 1, Jan-Feb

10 TMS is a Safer Treatment TMS scores highest in patient satisfaction measure SNAE = Sustained pain free with No Adverse Events Efficacy: % patients sustained pain 24 hrs (SPF) Tolerability: (1-AE) % Adverse Events (AE) SNAE score: % SPF(1-AE) Triptan Average 20.0% 64.3% 12.8% TMS 29.3% b 95.1% bb 27.8% bbb Higher SNAE scores = better treatment outcome Source: Triptan SNAE Scores - Use of the Sustained Pain-Free Plus No Adverse Events Endpoint in Clinical Trials of Triptans in Acute Migraine; Dodick et al CNS Drugs 2007 TMS SNAE Scores- Neuralieve Migraine with Aura Study Data, 2008

11 Immediate Target Market Triptan Contra-Indicated Patients Estimated 5.5M patients cannot be treated SAFELY with triptans Pregnancy t 5M pregnancies per year in US ~ 1M lactation (assumes 75% women nursing for 3 months) t 25% migraine prevalence in child bearing age women 1.5M potential patients can not be served by triptans Patients with cardiovascular or pulmonary risk factors t 10 million angina patients (largest group) t Assume 12% migraine prevalence general population 2M potential patients can not be served by triptans Patients taking anti-depressants (SSRI, SNRI; e.g.: Prozac, Zoloft) t 17 million people in US suffer major depression t Migraine sufferers 5 times more likely to develop major depression t Fatal triptan interaction warning from FDA* t Assume 12% migraine prevalence general population (likely higher) 2M potential patients cannot be served by triptan t BECAUSE OF THE FDA, 5.5M AMERICAN PATIENTS CANNOT HAVE THEIR SEVERE HEADACHES RELIEVED WITH THE NEURALIEVE TMS DEVICE BUT MUST SUFFER THE PAIN OF REPEATED MIGRAINE HEADACHES

12 PROBLEMS WITH FDA CLEARANCE Trial that was designed with the help of the FDA is completed successfully June (k) submitted July 2008 with 2 predicates FDA denies predicates in October 2008 De novo 510(k) filed in November 2008 FDA missed reuired 60 day deadline to respond and there was no recourse to get them to respond Summer 2009 FDA branch chief states that because the TMS device would be very popular they must have a higher standard of efficacy for it to be approved. FDA states that we should have a panel meeting to review the data (like for a high risk PMA type device); This is unprecedented. November 2009 FDA delays panel until February 2010

13 PROBLEMS WITH FDA CLEARANCE January 2010 FDA denies our application, no panel, says the device failed to show that it was effective, cites concerns about nausea and safety and now wants a PMA with a huge additional study April 2010 The Lancet medical journal publishes the trial results, authored by the current American Headache Society (AHS) President, the past AHS President and the President of the International Headache Society, saying that TMS is a safe and effective cure for migraine headaches The thought leader in migraine for Germany publishes an editorial in the same Lancet issue stating that the trial was very well designed May 2010 Neuralieve receives a letter from the world leaders in migraine headache that strongly disagrees with the FDA conclusions that the device is not safe and effective June 2010 HEADACHE, the journal of the American Headache Society publishes a Review Article with the President of that Society as the lead author with the conclusion; The safety of stms in clinical practice, including as an acute migraine headache treatment, is supported by biological, empirical, and clinical trial evidence.

14 CONCLUSIONS REGARDING TMS FOR MIGRAINE There is no longer an appeals process that works in the FDA to overrule the lowest level of review, thus the company must commercialize overseas to raise money and cannot hire Americans into good paying jobs as a result More than 5 million American patients who cannot take migraine medications are denied this safe and effective therapy and therefore must suffer 10s of millions of severe migraine headaches without help from a device that has been proven in clinical studies to be safe and effective Some Americans will be able to go to Europe to get the device to treat their migraine headaches; but the vast majority of American migraine patients will not have ready access to the TMS device

15 TMS FOR TREATING MIGRAINE HEADACHE CONCLUSION TIME FOR QUESTIONS?