Dear supporters of Hope NOW for ALS, Please email Congress before Friday to ask for their continued support. Due to the upcoming recess, this week is our only opportunity to request their support before our next teleconference with the FDA on July 6. On June 17, we conducted a teleconference with the FDA and we can report some progress, but also some concerns. The good news is the FDA agrees that: 1) FVC is a valid clinical endpoint, 2) trials can be populated with “fast progressors,” and 3) an ALS therapy could be approved after a Phase II study if it resulted in a clinically significant, positive effect on FVC decline. FDA described what they meant by clinically significant as “compelling, convincing evidence” between the treated group and the control (placebo) group. The FDA’s position on potential ALS biomarkers is that none have been validated and, therefore, none can be used as surrogates to support an accelerated approval, but they did assure us that collecting data on potential biomarkers would not be used as evidence against approval of an ALS drug if a correlation between the marker and the primary endpoint (for example FVC) is not seen. Also, FDA agreed that measurement of potential biomarkers could be included in a study to enhance understanding of their relationship to ALS. FDA provided some general responses on how an ALS biomarker could be validated, but did not progress to details. We proposed the concept that small clinical studies can produce sufficient evidence of efficacy to support an approval, especially if progression prediction models are employed to appropriately select the trial population or to establish individual patient baselines. The FDA expressed openness to learning more about predictive algorithms. During discussions of some of the potential biomarkers for ALS, it appeared that the FDA’s Division of Neurology Products (DNP) medical review officers (Drs. Eric Bastings and Ronald Farkas) were unfamiliar with the state of biomarker science in ALS. We hope this is not the case, and we intend to explore and build their knowledge of the state of medical science with respect to ALS during our ongoing communications. Based on our discussions during the meeting, we are also concerned that the FDA is employing a very narrow, rigid and outdated view of the circumstances in which the Accelerated Approval pathway should be available to drug companies trying to bring new medicines to market. Dr. Woodcock made the FDA’s position on Accelerated Approval very clear by stating that in FDA’s mind there is nothing fast about Accelerated Approval, and they wish they hadn’t called it that. Her position on the Congressional intent of Accelerated Approval seems to be at odds with the directions FDA received from Congress in the 2012 FDASIA legislation, which made it clear that FDA is to apply new thinking, flexibility and an expanded set of evidentiary tools to speed new medicines to patients who need them for diseases like ALS. This issue will be discussed again at the next meeting since Accelerated Approval is clearly intended for diseases like ALS for which there is no effective treatment. We are also concerned with the subjectivity the FDA maintains in determining what constitutes efficacy and “convincing evidence.” We intend to press the FDA for a clear definition of efficacy for a given trial design that could result in quickly accepting a new drug application (NDA). This is particularly relevant to GM604 in order to define a small, confirmatory study that could result in its approval if the results meet the definition of efficacy. We also believe this will create a template for future ALS treatment options. As mentioned earlier in this update our next conference call is scheduled on July 6 and this call should determine if Dr. Woodcock and the FDA will be reasonable and demonstrate flexibility as Congress intended. Using the template below please email your congress before Friday and request their continued support. Remember, the best way to follow breaking news items that affect our campaign is to follow us on Facebook: https://www.facebook.com/gm604forals We're in this together, Jehad Majed (jmajed@mac.com), Matthew Bellina, Nick Grillo (gm6nick@gmail.com), and the Torrino Family WHAT TO INCLUDE: #### [Start with any opening you like – BUT BE SURE TO INCLUDE ANY OF THE FOLLOWING THAT REFLECTS YOUR VOICE] HopeNOWforALS.org had a conference call with the FDA on June 17 to discuss a pathway forward for the evaluation of investigational treatments for ALS. Here is the update from that call: http://tinyurl.com/qfpnqbw The FDA’s current, inflexible, years-long process for bringing new ALS drugs to market is failing to meet the needs of PALS and needs to be a process where the FDA views the patient community as full and equal partners. By the FDA’s own admission, "It can take too long for an investigational treatment to definitively demonstrate a clinical benefit and then go through the process of securing FDA approval." On the website, the FDA claims that the 1992 Accelerated Approval Program is a way to speed new drugs to market that treat serious diseases and fill an unmet medical need. If this program isn’t meant to address ALS, then I want to know what does constitute a “serious” and “unmet medical need"! The FDA, particularly the Department of Neurology Products, has to stop refusing to use the Accelerated Approval Program (AAP) in the manner intended by Congress and start meeting the needs of populations like the ALS Community. This is something that should have been done two decades ago when AAP became policy. Please stand with the patient community and contact Dr. Woodcock on my behalf. Please tell her that you see the FDA's refusal to implement the Accelerated Approval Program for safe, promising treatments being developed for orphan diseases like ALS is a clear signal that she is not meeting the intent of the 2012 FDASIA. The time and expense it requires to follow the FDA's antiquated regulatory process has made it impossible to get any viable treatment option to patients like me and utilizing the Accelerated Approval Program as it was intended, with Phase 4 marketing requirements, is the fastest and cheapest way to collect data on these promising new treatments that have demonstrated safety in Phase 1 and 2 clinical trials. ##### US SENATORS Alabama Sessions, Jeff - (R - AL) (202) 224-4124 http://www.sessions.senate.gov/public/index.cfm/contact-jeff Shelby, Richard C. - (R - AL) (202) 224-5744 http://www.shelby.senate.gov/public/index.cfm/emailsenatorshelby Alaska Murkowski, Lisa - (R - AK) 202) 224-6665 http://www.murkowski.senate.gov/public/index.cfm/emaillisa Sullivan, Daniel - (R - AK) (202) 224-3004 http://www.sullivan.senate.gov/content/contact-dan Arizona Flake, Jeff - (R - AZ) (202) 224-4521 http://www.flake.senate.gov/public/index.cfm/contact-jeff McCain, John - (R - AZ) (202) 224-2235 http://www.mccain.senate.gov/public/index.cfm/contact-form Arkansas Boozman, John - (R - AR) (202) 224-4843 http://www.boozman.senate.gov/public/index.cfm/e-mail-me Cotton, Tom - (R - AR) 202) 224-2353 http://www.cotton.senate.gov/content/contact-tom California Boxer, Barbara - (D - CA) (202) 224-3553 https://www.boxer.senate.gov/contact/shareyourviews.html Feinstein, Dianne - (D - CA) (202) 224-3841 https://www.feinstein.senate.gov/public/index.cfm/e-mail-me Colorado Bennet, Michael F. - (D - CO) (202) 224-5852 http://www.bennet.senate.gov/?p=contact Gardner, Cory - (R - CO) (202) 224-5941 http://www.gardner.senate.gov/content/contact-cory Connecticut Blumenthal, Richard - (D - CT) (202) 224-2823 https://www.blumenthal.senate.gov/contact Murphy, Christopher - (D - CT) (202) 224-4041 http://www.murphy.senate.gov/contact Delaware Carper, Thomas R. - (D - DE) (202) 224-2441 http://www.carper.senate.gov/public/index.cfm/email-senator-carper Coons, Christopher A. - (D - DE) (202) 224-5042 http://www.coons.senate.gov/contact/ Florida Nelson, Bill - (D - FL) (202) 224-5274 http://www.billnelson.senate.gov/contact-bill Rubio, Marco - (R - FL) (202) 224-3041 http://www.rubio.senate.gov/public/index.cfm/email-senator-rubio?p=Contact Georgia Isakson, Johnny - (R - GA) (202) 224-3643 http://www.isakson.senate.gov/public/index.cfm/email-me Perdue, David - (R - GA) (202) 224-3521 http://www.perdue.senate.gov/content/contact-david Hawaii Hirono, Mazie K. - (D - HI) (202) 224-6361 http://www.hirono.senate.gov/contact/email Schatz, Brian - (D - HI) (202) 224-3934 http://www.schatz.senate.gov/contact Idaho Crapo, Mike - (R - ID) (202) 224-6142 http://www.crapo.senate.gov/contact/email.cfm Risch, James E. - (R - ID) (202) 224-2752 http://www.risch.senate.gov/public/index.cfm/email Illinois Durbin, Richard J. - (D - IL) (202) 224-2152 http://www.durbin.senate.gov/contact/email Kirk, Mark - (R - IL) (202) 224-2854 http://www.kirk.senate.gov/?p=comment_on_legislation Indiana Coats, Daniel - (R - IN) (202) 224-5623 http://www.coats.senate.gov/contact/ Donnelly, Joe - (D - IN) (202) 224-4814 http://www.donnelly.senate.gov/contact/email-joe Iowa Ernst, Joni - (R - IA) (202) 224-3254 http://www.ernst.senate.gov/content/contact-joni Grassley, Chuck - (R - IA) (202) 224-3744 http://www.grassley.senate.gov/constituents/questions-and-comments Kansas Moran, Jerry - (R - KS) (202) 224-6521 http://www.moran.senate.gov/public/index.cfm/e-mail-jerry Roberts, Pat - (R - KS) (202) 224-4774 http://www.roberts.senate.gov/public/index.cfm?p=EmailPat Kentucky McConnell, Mitch - (R - KY) (202) 224-2541 http://www.mcconnell.senate.gov/public/index.cfm?p=ContactForm Paul, Rand - (R - KY) (202) 224-4343 http://www.paul.senate.gov/?p=contact Louisiana Cassidy, Bill - (R - LA) (202) 224-5824 http://www.cassidy.senate.gov/content/contact-bill Vitter, David - (R - LA) (202) 224-4623 http://www.vitter.senate.gov/contact/email-senator-vitter Maine Collins, Susan M. - (R - ME) (202) 224-2523 http://www.collins.senate.gov/public/index.cfm/email King, Angus S., Jr. - (I - ME) (202) 224-5344 http://www.king.senate.gov/contact Maryland Cardin, Benjamin L. - (D - MD) (202) 224-4524 http://www.cardin.senate.gov/contact/ Mikulski, Barbara A. - (D - MD) (202) 224-4654 http://www.mikulski.senate.gov/contact Massachusetts Markey, Edward J. - (D - MA) (202) 224-2742 http://www.markey.senate.gov/contact Warren, Elizabeth - (D - MA) (202) 224-4543 http://www.warren.senate.gov/?p=email_senator Michigan Peters, Gary - (D - MI) (202) 224-6221 http://www.peters.senate.gov/content/contact-gary Stabenow, Debbie - (D - MI) (202) 224-4822 http://www.stabenow.senate.gov/?p=contact Minnesota Franken, Al - (D - MN) (202) 224-5641 http://www.franken.senate.gov/?p=email_al Klobuchar, Amy - (D - MN) (202) 224-3244 http://www.klobuchar.senate.gov/public/email-amy Mississippi Cochran, Thad - (R - MS) (202) 224-5054 http://www.cochran.senate.gov/public/index.cfm/email-me Wicker, Roger F. - (R - MS) (202) 224-6253 http://www.wicker.senate.gov/public/index.cfm/contact Missouri Blunt, Roy - (R - MO) (202) 224-5721 http://www.blunt.senate.gov/public/index.cfm/contact-roy McCaskill, Claire - (D - MO) (202) 224-6154 http://www.mccaskill.senate.gov/contact Montana Daines, Steve - (R - MT) (202) 224-2651 http://www.daines.senate.gov/content/contact-steve Tester, Jon - (D - MT) (202) 224-2644 http://www.tester.senate.gov/?p=email_senator Nebraska Fischer, Deb - (R - NE) (202) 224-6551 http://www.fischer.senate.gov/public/?p=email-deb Sasse, Ben - (R - NE) (202) 224-4224 http://www.sasse.senate.gov/content/contact-ben Nevada Heller, Dean - (R - NV) (202) 224-6244 http://www.heller.senate.gov/public/index.cfm/contact-form Reid, Harry - (D - NV) (202) 224-3542 http://www.reid.senate.gov/contact New Hampshire Ayotte, Kelly - (R - NH) (202) 224-3324 http://www.ayotte.senate.gov/?p=contact Shaheen, Jeanne - (D - NH) (202) 224-2841 http://www.shaheen.senate.gov/contact/ New Jersey Booker, Cory A. - (D - NJ) (202) 224-3224 http://www.booker.senate.gov/?p=contact Menendez, Robert - (D - NJ) (202) 224-4744 http://www.menendez.senate.gov/contact New Mexico Heinrich, Martin - (D - NM) (202) 224-5521 http://www.heinrich.senate.gov/contact/write-martin Udall, Tom - (D - NM) (202) 224-6621 http://www.tomudall.senate.gov/?p=contact New York Gillibrand, Kirsten E. - (D - NY) (202) 224-4451 http://www.gillibrand.senate.gov/contact/ Schumer, Charles E. - (D - NY) (202) 224-6542 http://www.schumer.senate.gov/contact/email-chuck North Carolina Burr, Richard - (R - NC) (202) 224-3154 http://www.burr.senate.gov/public/index.cfm?FuseAction=Contact.ContactForm Tillis, Thom - (R - NC) (202) 224-6342 http://www.tillis.senate.gov/content/contact-thom North Dakota Heitkamp, Heidi - (D - ND) (202) 224-2043 http://www.heitkamp.senate.gov/public/index.cfm/email-heidi Hoeven, John - (R - ND) (202) 224-2551 http://www.hoeven.senate.gov/public/index.cfm/email-the-senator Ohio Brown, Sherrod - (D - OH) (202) 224-2315 http://www.brown.senate.gov/contact Portman, Rob - (R - OH) (202) 224-3353 https://www.portman.senate.gov/public/index.cfm/contact-form Oklahoma Inhofe, James M. - (R - OK) (202) 224-4721 http://www.inhofe.senate.gov/contact Lankford, James - (R - OK) (202) 224-5754 http://www.lankford.senate.gov/content/contact-james Oregon Merkley, Jeff - (D - OR) (202) 224-3753 http://www.merkley.senate.gov/contact Wyden, Ron - (D - OR) (202) 224-5244 http://www.wyden.senate.gov/contact Pennsylvania Casey, Robert P., Jr. - (D - PA) (202) 224-6324 http://www.casey.senate.gov/contact Toomey, Patrick J. - (R - PA) (202) 224-4254 http://www.toomey.senate.gov/?p=contact Rhode Island Reed, Jack - (D - RI) (202) 224-4642 http://www.reed.senate.gov/contact/email Whitehouse, Sheldon - (D - RI) (202) 224-2921 http://www.whitehouse.senate.gov/contact/ South Carolina Graham, Lindsey - (R - SC) (202) 224-5972 http://www.lgraham.senate.gov/public/index.cfm?FuseAction=Contact.EmailSenatorGraham Scott, Tim - (R - SC) (202) 224-6121 http://www.scott.senate.gov/contact/email-me South Dakota Rounds, Mike - (R - SD) (202) 224-5842 http://www.rounds.senate.gov/content/contact-mike Thune, John - (R - SD) (202) 224-2321 http://www.thune.senate.gov/public/index.cfm/contact Tennessee Alexander, Lamar - (R - TN) (202) 224-4944 http://www.alexander.senate.gov/public/index.cfm/email Corker, Bob - (R - TN) (202) 224-3344 http://www.corker.senate.gov/public/index.cfm/emailme Texas Cornyn, John - (R - TX) (202) 224-2934 http://www.cornyn.senate.gov/public/index.cfm?p=ContactForm Cruz, Ted - (R - TX) (202) 224-5922 http://www.cruz.senate.gov/?p=email_senator Utah Hatch, Orrin G. - (R - UT) (202) 224-5251 http://www.hatch.senate.gov/public/index.cfm/email-orrin Lee, Mike - (R - UT) (202) 224-5444 http://www.lee.senate.gov/public/index.cfm/contact Vermont Leahy, Patrick J. - (D - VT) (202) 224-4242 https://www.leahy.senate.gov/contact/ Sanders, Bernard - (I - VT) (202) 224-5141 http://www.sanders.senate.gov/contact/comment Virgina Kaine, Tim - (D - VA) (202) 224-4024 https://www.kaine.senate.gov/contact Warner, Mark R. - (D - VA) (202) 224-2023 http://www.warner.senate.gov/public/index.cfm?p=ContactPage Washington Cantwell, Maria - (D - WA) (202) 224-3441 http://www.cantwell.senate.gov/public/index.cfm/email-maria Murray, Patty - (D - WA) (202) 224-2621 http://www.murray.senate.gov/public/index.cfm/contactme West Virginia Capito, Shelley Moore - (R - WV) (202) 224-6472 http://www.capito.senate.gov/content/contact-shelley Manchin, Joe, III - (D - WV) (202) 224-3954 http://www.manchin.senate.gov/public/index.cfm/contact-form Wisconsin Baldwin, Tammy - (D - WI) (202) 224-5653 http://www.baldwin.senate.gov/contact Johnson, Ron - (R - WI) (202) 224-5323 http://www.ronjohnson.senate.gov/public/index.cfm/email-the-senator Wyoming Barrasso, John - (R - WY) (202) 224-6441 http://www.barrasso.senate.gov/public/index.cfm/contact-form Enzi, Michael B. - (R - WY) (202) 224-3424 http://www.enzi.senate.g ov/public/index.cfm/e-mail-senator-enzi