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Pink Sheet – No Sweat – Hyperhidrosis Patients Seek Broader Approvals; Botox Access An Issue

Pink Sheet – No Sweat – Hyperhidrosis Patients Seek Broader Approvals; Botox Access An Issue

Executive Summary


US FDA not looking to reduce attendance at third-party patient meetings, which deliver ‘bang for the buck.’ Excessive sweating is first externally led PFDD meeting for a more common condition.


Drug sponsors interested in hyperhidrosis research and development should focus on treatments that are effective for all types of excessive sweating – not just underarm or foot/hand sweating, according to patients participating in a patient-focused drug development meeting hosted by the International Hyperhidrosis Society in Washington, DC on Nov. 13.


While there are treatments for hyperhidrosis approved by the US FDA – like Botox injections and DrySol prescription antiperspirant – they are not a realistic option for all areas where patients present with excessive sweating. Hyperhidrosis of the groin/buttocks or face/head are especially hard to treat, and off-label treatments are not always effective. Furthermore, Botox is only FDA-approved for underarm sweating, and is therefore not covered by payors for other body areas.


The hyperhidrosis meeting offered a lesson for other groups planning externally-led patient-focused drug development (PFDD) meetings: leave more time to discuss specific endpoints to help guide industry R&D efforts. Much of the discussion was focused on conveying patient stories, but the meeting ran long, and there was little time for patients to talk about new treatment options or to make recommendations about clinical trial endpoints.


One International Hyperhidrosis Society board member, David Pariser (Eastern Virginia Medical School), was able to sum up his thoughts on those topics in closing remarks, and he argued that the clinical trial endpoints need to be reconsidered. Bona fide hyperhidrosis patients, he said, are often denied access to a clinical trial because the gravimetric assessment used to determine whether a patient meets the “sweat threshold” does not capture everyone.


FDA’s Sherman underscored the importance of the post-PDUFA V patient-focused drug development meetings, saying that they deliver an “enormous bang for the buck.”


“You don’t sweat the same amount 24/7,” Pariser said. “Some do, but it is variable. And if you have to hit a certain gravimetric minimum – meaning you have to sweat a certain amount, at that very moment when you are in the doctor’s office. You may not be sweating that day, and you may be denied access to a clinical trial because of it.”


The hyperhidrosis meeting is the latest in a wave of externally-led patient focused-drug development meetings. At least 10 third-party meetings have been held over the past two years, including those for amyloidosis, spinal muscular atrophy, Friedreich’s Ataxia, and most recently, lupus. While FDA is not announcing the meetings nor keeping official track of them, the agency says it has found the discussions valuable. (See sidebar.)


Speaking at the Biopharma Congress hosted by Prevision Policy and Friends of Cancer Research Nov. 14, FDA Principal Deputy Commissioner Rachel Sherman underscored the importance of the post-PDUFA V patient-focused drug development meetings, saying that they deliver an “enormous bang for the buck.” When asked if divisions would need to start prioritizing externally led PFDD meetings due to resource constraints, Sherman said “this is not a place where we want to cut back.”


Hyperhidrosis is the first externally-led PFDD meeting for a condition that falls under the purview of the Division of Dermatology & Dental Products. DDDP organized meetings for psoriasis and alopecia areata as part of the 24 FDA-led PFDD meetings convened as part of the Prescription Drug User Fee Act agreement. Now that those FDA-led meetings have concluded, the agency has said it will attend as many third-party meetings as possible, and will encourage drug developers to attend as well.


FDA Division of Dermatology & Dental Products Director Kendall Marcus delivered general opening remarks to the hyperhidrosis meeting about the drug development process, and then went into listen-only mode. Two other FDA officials from the division were in the audience: Deputy Director for Safety Tatiana Oussuva and Medical Officer Melissa Reyes. Meghana Chalasani from the Office of Strategic Programs, who has moderated many of the FDA-led sessions, was also in attendance.


The meeting was hosted by the International Hyperhidrosis Society, a global non-profit patient advocacy organization founded in 2003. The PFFD meeting was supported by a number of IHS corporate partners: Dermira Inc. (two investigational treatments, glycopyrronium tosylate and olumacostat glasaretil are in late-stage clinical trials), RA Fischer and Hidrex (both market iontophoresis machines) and Brickell Biotech (sofpironium bromide is in Phase II trials).

A Common Condition With Few Treatments

Unlike most of the preceding externally-led PFDD meetings, hyperhidrosis is (by some definitions at least) an extremely common condition. Recent studies suggest a worldwide prevalence rate of 4.8%, including 15.3 million people in the U.S. The average age of onset is 25 years old, and a family history is apparent in 30%-65% of cases.


Hyperhidrosis patients used the first half of the meeting to discuss the impact of their condition on their quality of life: telling stories about needing to change clothes several times a day, shorting out computer keyboards (or suffering electrical shocks), dropping objects from slippery hands (participants were especially worried about holding babies), being afraid to shake hands with others and sweating through their shoes.


Many of the patient participants on the panels were young (20s and 30s), underscoring the early age of onset for hyperhidrosis. As a sign of the day-to-day adjustments required by patients, boxes of tissues were made available on both the stage and audience tables for participants to wipe their sweaty hands. Many of the presenters carried copies of their remarks in plastic covers so as to not smear the ink as they held the paper.


The lack of an effective treatment forces patients to self-treat or self-regulate their body temperature. Participants talked about using a hair dryer to dry underarm sweat stains, keeping air conditioning on high year-round, wearing fans around their necks to cool their face and head, or using adult diapers to collect sweat in the groin area (or women avoiding pants altogether in favor of skirts or dresses). One patient, Sachin, built a homemade iontophoresis machine out of aluminum pie plates and batteries.


Patients said they needed more effective and safe minimally invasive treatments. The limited FDA-approved and off-label treatment options include:

  • Non-invasive: Topical antiperspirants (like DrySol); iontophoresis (mild electrical currents through water and into the skin); anticholinergics like Robinul (glycopyrrolate) and oxybutynin.
  • Minimally invasive: Botulinum injections (Botox, Dysport, Myobloc) to temporarily paralyze sweat glands; microwave thermolysis (miraDry) to destroy sweat glands in the underarm.
  • Surgical: Local excision, subcutaneous curettage or liposuction of axillary tissue; endoscopic thoracic sympathectomy (ETS) surgery.

Patients with underarm or hand/feet sweating tend to start with DrySol and move to botulinum injections upon treatment failure. Iontophoresis is an option favored by many parents of children with hyperhidrosis as it is not invasive, but it requires multiple doctor visits per week. Anticholinergics are most often used off-label for hand/face sweating, but they can cause severe dry mouth and dry eyes. ETS surgery used to be promoted as a “quick fix” but it is expensive ($20,000 for a 20-minute procedure) and has been found to cause compensatory sweating elsewhere on the body.

Botox Access An Issue For Many

Many patients found Botox injections to be highly effective in treating underarm or hand/foot sweating, and were willing to endure the painful injections (as many as 100 needle sticks) to treat their condition. But access is a significant barrier to Botox treatment as payors rarely cover the procedure, and patients are forced to pay out of pocket for treatments up to four times a year.


One patient, Michelle, noted that she reserves Botox for “special occasions,” like her wedding, where the cost of the injections needed to keep her dry was factored into her wedding budget.


Another patient, Wendy, illustrated the side effects that patients will endure for an effective treatment. After she was unable to access Botox due to a change in insurance, she tried the oral anticholinergic Robinul (glycopyrrolate). Robinul works for her, but causes extreme dry eye and dry mouth, and at least 15 “crippling” leg cramps a night. Despite those side effects, she stays on therapy. “We shouldn’t have to suffer these side effects,” Wendy said. “There has to be a better option out there.”


In his closing remarks, Pariser pushed drug sponsors to come up with accessible treatment options. “As new things are developed, are they going to be costly, designer drugs for people who can pay cash, like miraDry, or are they going to be drugs that are going to be more equally available?”–Hyperhid…