Botanix Pharmaceuticals Limited (ASX:BOT) is a Perth-based company. Its main asset is Sofpironium Bromide (SOFDRA), which it aims to use as a treatment for Primary Axillary Hyperhidrosis (PAH). It does have two other programs that have completed a Phase 1/2 trial; however, they are on hold until the commercialisation of Sofpironium Bromide. Sofpironium Bromide, or SOFDRA, contains 15% of Sofpironium Bromide. Currently, Japan has 5% available for the treatment of PAH.
Upcoming Catalysts
The main upcoming event is the potential approval for Sofpironium Bromide to treat Primary Axillary Hyperhidrosis, which is excessive sweating in the armpits. The company previously submitted a New Drug Application (NDA) and received a Complete Response Letter (CRL) on September 26, 2023, which required changes to the product labelling. The NDA was resubmitted on December 21, 2023, with a Prescription Drug User Fee Act (PDUFA) date of June 20.
Disease
Primary axillary hyperhidrosis is a condition characterised by excessive sweating of the underarms without a clear cause. This is due to the overactivation of cholinergic receptors in eccrine glands caused by the excessive release of acetylcholine from the nerve endings. It is theorised that the negative feedback loop from the hypothalamus is impaired, thus causing excessive sweating. The most commonly affected areas are the armpits, palms, soles, and face.
https://www.ncbi.nlm.nih.gov/books/NBK459227/
Prevalence/Total Addressable Market (TAM)
It is estimated that approximately 3% or 15 million patients of the US population suffer from Primary Hyperhidrosis. The prevalence of axillary hyperhidrosis is 50%, and outside of the US, it is estimated at 4.6% in Germany, 12.3% in Sweden, 12.8% in Japan, and 14.5% in China.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099353/
The total addressable market is estimated to be 1.6 billion dollars, with the TAM expected to be 2.8 billion in 2030. This information is derived from a company investor presentation.
Treatment Options
Aluminium chloride is used to block the sweat glands as a treatment for axillary hyperhidrosis, but it can cause skin irritation as a common side effect. There is also growing concern about the potential increased risk of cancer, dementia, and other diseases due to exposure to aluminium.
Topical glycopyrrolate has shown improvement in treating hyperhidrosis, but there is systematic absorption of the drug, leading to standard cholinergic side effects. This is also the case with oxybutynin, a treatment for overactive bladder, which also has many systemic cholinergic side effects. Systemically using these drugs as an oral tablet can effectively reduce perspiration, but the systemic cholinergic side effects can be severe.
Iontophoresis is suitable for treating plantar and palmar hyperhidrosis methods such as microwave thermolysis, radiofrequency therapy, ultrasounds, and laser treatment, which aim to destroy the eccrine gland and reduce sweating.
Botox injections are highly effective in treating axillary hyperhidrosis and can last from 6 to 24 months from the time of injection.
Finally, there are surgical options available. Retrodermal curettage is the mechanical removal of the sweat glands. Sympathectomy is a very invasive procedure in which the sympathetic nerve is either cut or tied off to prevent it from stimulating the gland and preventing sweating.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131949/#cit0031, https://www.ncbi.nlm.nih.gov/books/NBK459227/#article-23177.s9
FDA
The initial New Drug Application (NDA) was submitted to the FDA on September 26, 2022, and the review will commence on December 8, 2022. In April 2023, the company announced that the FDA had a mid-cycle review meeting and identified no significant issues. On September 26, 2023, Botanix received a complete response letter for Sofpironium Bromide, which was 15% in PAH. The company stated that the only areas needing to be addressed were the patient instructions and the wording on the product carton. In December, the company confirmed that the planned materials and changes to be submitted by Botanix were suitable for resubmission after the review meeting with the FDA. This included the Human Factors study protocol and report, an updated use-related risk analysis of the product, updated draft prescribing information, carton and container labels, and proprietary name approval. A human factors study was completed on December 14 with the modified instructions for use, and on December 21, 2023, an NDA was resubmitted. In January, the FDA confirmed that the resubmission was accepted with a PDUFA date of June 20, 2024.
Sofpironium Bromide – Sofdra
As a derivative of Glycopyrronium bromide, which is currently used to treat Hyperhidrosis both topically and orally, Sofpironium Bromide is considered a soft anticholinergic medication. It works by blocking the action of acetylcholine, which prevents the activation of sweat glands. It is designed to work locally through retrometabolic processes. After being absorbed into the blood, the medication is quickly metabolised into a less active form, which then circulates through the bloodstream and exhibits anticholinergic properties.
The Japanese FDA has already approved the drug at a 5% concentration for PAH, and currently, there are P1 trials for primary palmoplanter hyperhidrosis in Japan’s 5% formulation.
Clinical Trial Data
Pilot study: This double-blind clinical study involved 18 subjects with PAH in 3 groups: high concentration, low concentration, or topical vehicle. 75% of subjects received more than 50% sweat reduction compared to 33% of the subjects in the vehicle group.
Multicentre randomised double-blind, placebo-controlled P2b study comparing 5%,10%15% or placebo. 38.3% with 15mg vs 12.2% with vehicle improvement without a significant jump in adverse with higher doses.5% and 15% dose groups, responders with a 1-point (86.1%; 85.8%) and 2-point (69.4%; 61.9%) improvement on HDSM-Ax PRO scale
Cardigan I NCT03836287 and Cardigan II NCT03948646 2 Phase 3 trials.
A study evaluated the effects of a 15% solution in treating primary axillary hyperhidrosis (PAH). The study involved 350 subjects aged nine years and older with PAH. The treatment involved applying the 15% solution once daily at bedtime for six consecutive weeks, followed by a 2-week post-treatment follow-up. The evaluation included a 2-point improvement on the Hyperhidrosis Disease Severity Measure Axillary (HDSM-Ax) and measurement of Gravimetric Sweat Production (GSP) from baseline to the end of treatment.
The daily treatment was well tolerated over the 48 weeks of assessment for treatment efficacy, showing clinically meaningful and sustained improvement in sweat severity. The 5% and 15% solutions for PAH were applied once daily at bedtime for 48 weeks, and the study showed that the treatment was effective for patients nine years and older. A 4-week post-treatment visit was conducted.
Adverse Events 5% – 22.5% and 15% -50.8%
blurred vision (4.9%; 18.8%), dry mouth (8.8%; 16.8%), pruritis (5.9%; 14.7%), pain (3.9%; 14.7%), dermatitis (5.9%; 9.1%), erythema (4.9%; 7.6%), irritation (4.9%; 5.6%), mydriasis (1.0%; 5.1%) and urinary retention (2.9%; 3.6%).
The patient discontinuations due to treatment-related TEAEs included blurred vision (2.0%; 7.1%), pruritis (0%; 2.0%), dermatitis (1.0%; 2.0%), dry mouth (0%; 1.5%), pain (0%; 1.5%), erythema (1.0%; 0.5%), irritation (0%; 1.0%), urinary hesitation (1.0%; 0%) and mydriasis (0%; 0.5%).
Discontinuation was reduced over time, and no serious adverse events were absorbed as acclimated to treatment.
Manufacturing
SOFDRA is considered a combination product 1. One is the actual drug API, and the other is the applicator.
Commercial-scale manufacturing has occurred during phase 3 clinical trials. The company’s suppliers meet CMC and GMP guidelines from the FDA, as they already provide products to other companies.
Licensing Deal and Royalties.
The company acquired an asset from Brikell Biotech in May 2022 and rebranded it as Freshtracks Therapeutics. An original licensing deal was put in place at that time. However, Botanix chose to buy out the future obligation for milestone payments and partial royalties for 8.25 million dollars, leaving only a 5% obligation to Bodor Labs on net sales and no milestones.
The company has licensed the Japanese and some Asian markets to Kaken Pharmaceuticals to commercialise Sofpironium Bromide 5%, marketed as ECCLOCK.Management
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This is not a recommendation or advice; it is just me writing up some of my research and publishing it on my blog. Please do your own research and speak to a professional because my research may be wrong or I have missed something please leave any suggestions in the comments.
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