Long Term Use of Novel Therapeutic for Topical Treatment of Primary Axillary Hyperhidrosis in Pediatric Subjects

By Medical Dermatology, ODAC Sessions No Comments

Source: ODAC Dermatology, Aesthetic & Surgical Conference (ODAC) Discovery in Dermatology Poster Session

At the 17th Annual ODAC Dermatology, Aesthetic, and Surgical Conference (ODAC) held January 17-20 in Orlando, FL, Brandon Kirsch, MD, Janet DuBois, MD, Martin N. Zaiac, MD and Deepak Chadha, MS, MBA, RAC presented scientific research of long term data with a novel therapeutic for topical treatment of primary axillary hyperhidrosis in pediatric subjects.

Discovery in Dermatology
The use of retro-metabolically designed drugs in dermatology is novel and has the potential for providing significant therapeutic benefit to pediatric and adult patients.

Sofpironium bromide is an ester analogue of glycopyrrolate that inhibits muscarinic receptors in sweat glands. It was developed according to the principles of retro-metabolic drug design, in which the goal is to create an active compound that is metabolized in vivo to an inactive moiety in a single, predictable reaction. Retro-metabolically designed drugs are rapidly metabolized in the bloodstream, potentially allowing for optimal therapeutic effect at application sites with minimal systemic side effects.

~2.1% of the US population aged <18 years has primary hyperhidrosis (HH); ~65% have axillary HH. Long-term safety/tolerability and efficacy of topical HH treatments have rarely been studied in pediatric patients. Sofpironium bromide is a retro-metabolically designed analog of glycopyrrolate (anticholinergic) in development for topical treatment of primary axillary HH. Absorbed drug is rapidly metabolized, potentially allowing optimal local therapeutic effect with minimal systemic effects..

21 of 25 subjects (age 9-16 yrs) with primary axillary HH of ≥6 months duration, completing a previous 1-week safety and pharmacokinetic (PK) study (BBI-4000-CL-105), were enrolled. Objectives were to assess safety/tolerability and PK, and explore efficacy of sofpironium bromide gel, 15% applied to both axillae for 24 weeks.

Mean age (SD) 13.3 (2.29) years. 16 subjects completed this 24-week study. 7 had treatment emergent adverse events (TEAEs); 4 with AEs related to study drug, including expected systemic anticholinergic AEs (blurred vision, dry mouth, dry eyes, mydriasis) and local events (pain, pruritus, rash, erythema). 2 subjects discontinued due to TEAEs, including dry eye, dry mouth, local pruritus, local rash. The majority (52.4%) of subjects did not have any local symptoms/signs, and none observed were severe in nature. PK did not show evidence of drug/major metabolite accumulation, with most subjects having concentrations not quantifiable. The validated patient-reported outcome, Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax), showed mean (SD) change from baseline (from previous study) to Week 24 of this study of -1.91 (1.038). A -1.00 change shows clinically meaningful improvement.

In this 24-week study in pediatric subjects sofpironium bromide, 15% was safe/well tolerated. Majority of subjects had no TEAE, and there were no severe or serious AEs. There was no evidence of drug accumulation. There was indication of clinically meaningful improvement in axillary HH.

Hyperhydrosis: Where are we?

By Medical Dermatology, ODAC Sessions
Hydrosis Chart

Source: Next Steps in Derm

Can you think of a skin condition that has a greater negative impact on quality of life than eczema or psoriasis?  That’s right, you guess it—hyperhidrosis!  I still remember my first hyperhidrosis patient who refused to shake people’s hands, go on dates, or attend social events due to his condition.  After his treatment, he was like a new man.  I can’t tell you how satisfying it was to see his life changed after treatment. That’s why I’m so excited to share what I learned from Dr. Adam Friedman at ODAC 2019 regarding hyperhidrosis.   Dr. Adam Friedman is Professor and Interim Chair of Dermatology, Residency Program Director, Director of Translational Research, and Director of the Supportive Oncodermatology Clinic in the Department of Dermatology at The George Washington University School of Medicine & Health Sciences.

Did You Know?

Nearly 5% of the world’s population suffers from hyperhidrosis—that’s 365 million people worldwide! In the U.S., 7.8 to 13.4 million people (2.8-4.8%) are estimated to be affected by hyperhidrosis—that’s comparable to the prevalence of psoriasis.  Spalding et al. showed that patients with hyperhidrosis reported a worse quality of life compared to those with atopic dermatitis or psoriasis (Value in Health 2003).  That made me raise my eyebrows for sure!

Hyperhidrosis stats
Spalding et al. Value in Health 2003;6(3):242(abstract)


Know Your Sweaters: First, Diagnose

Hyperhidrosis can be divided into primary (usually focal) and secondary (generalized).  For secondary hyperhidrosis, the underlying cause needs to be addressed, which may include drugs, cardiovascular disorders, respiratory failure, infections, malignancies, and metabolic disorders.  For primary hyperhidrosis, now, that’s where we dermatologists step in and save the day. So, what are our options?

Treatment Options

There are non-invasive, minimally invasive, and surgical options for the treatment of hyperhidrosis.  Here, we will discuss everything but surgical options and energy-based treatment.

  • Topical aluminum chloride, aluminum chloride hexahydrate, or aluminum zirconium trichlorohydrex
    • This is applied on skin overnight (to remain on skin for 6-8 hours, during non-sweating hours) and washed off in the morning before sweating begins
    • A non-medicated deodorant should be applied in the morning after showering
    • Can use topical steroids for skin irritation
    • Cons: itching and burning of skin, time-consuming, can damage fabrics, temporary relief
  • Inotophoresis
    • Need treatment for 20-30 minutes a session, 3-4 times a week. This can be effective (81-91% response), but who has time for that?
    • Cons: cumbersome, can be costly, long-term therapy, and again…time-consuming
  • Topical glycopyrronium tosylate (Qbrexa)—the new kid on the block! And he’s FDA-approved, too. Whoohoo!
    • This can be applied nightly onto clean skin and can be used in conjunction with an over-the-counter antiperspirant
    • Improvement can be expected in 1-3 weeks.
    • Can be used in kids (approved for >9 years of age)
    • Cons: anticholinergic side effects such as dry eyes, dry mouth, blurred vision (need to emphasize the need to wash hands thoroughly after use to minimize risk), long-term therapy, may be costly
  • Systemic anticholinergics: off-label use for hyperhidrosis
    • Glycopyrrolate
      • Can start at 1mg twice daily and increase up to 6mg a day, or until limited by anticholinergic side effects
    • Oxybutynin
      • Can start at 5 to 10mg daily and increase to 15 to 20mg daily
      • A study in kids showed a 90% response rate at 2mg daily.
    • Cons: again, anticholinergic side effects — ones listed above, as well as constipation, urinary retention, bradycardia, etc.
  • Beta-adrenergic blockers
    • This is great for patients with social phobias and performance anxiety!
    • Most can tolerate a dose of 10 to 20mg (to be taken 1 hour before). But don’t forget to check the resting blood pressure and heart rate beforehand!  Oh, and also, they need a “test run” at home, just to make sure all goes smoothly before the actual “showtime”.
    • Contraindications: bradycardia, AV block, asthma
  • Botulinum toxin injection
    • Before treatment: patients should avoid deodorants for 24 hours prior and rest comfortably for 30 minutes prior
    • Treatment: after making an outline of the area, inject at a depth of 2mm, at a 45 degree angle with the bevel up, 1-2cm apart
    • What to expect: onset is about 2-4 days and duration is 3-7 months
    • Other considerations
      • Topical analgesics help a ton!
      • Do not use sterile water—can sting
      • If you buy the toxin and inject, use the CPT code 64650 and J code J0585 (with units)
      • If you prescribe the toxin to a pharmacy, provider bills only for the injection service, and patient pays co-pay for both the toxin and injections
    • Cons: can be painful and expensive

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Hyperhydrosis: Where Are We Now?

By Medical Dermatology, ODAC Sessions
Video of Dr. Adam Friedman

Source:Dermatology News

When you extend your hand to a new patient, and he reflexively wipes his palm before shaking hands, be alert. It’s possible you’re seeing primary hyperhidrosis, a condition that’s both more common and more disabling than once thought.

“Looking at the biology of sweating, normally, it’s a good thing – we need it to survive. However, hyperhidrosis is too much of a good thing – it’s an excess of what is needed for normal biology,” said Adam Friedman, MD, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.

Recent data, he pointed out, show that hyperhidrosis is more prevalent than previously thought – about 4.8% of individuals may have the condition, with about half having axillary hyperhidrosis. Symptoms peak in early adulthood, with adults aged 18-54 most affected. “These are the prime working years,” he said.

About 2% of teens are affected, and many adults report that symptoms began before they were 12 years old. Hand hyperhidrosis is a factor for computer and electronic device work, sports, and even handling paper and pencils, noted Dr. Friedman, professor of dermatology at George Washington University, Washington.

“Does it affect quality of life? Yes. We have data to support the impact. The adverse impact is actually greater than that of eczema and psoriasis,” he said, adding that patients won’t always bring up their concerns about sweating. “Often, it’s the patient who apologizes for having sweaty palms or who sticks to the paper on the exam table. It’s worth asking these patients if they are bothered by excessive sweating.”

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