Acrux (ACR: $0.012) has licensed rights for its spray-on HRT (hormone replacement therapy) product Lenzetto for the Australian market to Gedeon Richter Plc. Acrux stands to receive $5.4 million under the deal upon the achievement of milestones.
The milestone payments, of which there are three, should be met. The first is payable 14 days from signing of the deal (now payable). The second is due upon regulatory approval. (The product is sold by Gedeon Richter in more than 40 countries, as well as being sold in the US by Padagis under the brand name Evamist.) And the third is due two years from product launch in Australia.
The interest in HRT products has been resurrected following acknowledgement that risks stated from this product class had been incorrect. In January this year the FDA removed black box warnings on HRT medicines, which had previously been linked to breast cancer, cardiovascular disease and dementia.
According to Acrux CEO John Warmbrunn, sales of HRT products have doubled in Australia in the last year, tripled in the UK over the same period, and sales are growing at 35% a year in the US. Acrux still receives a small ongoing royalty from Evamist sales in the US from Padagis. In January 2023, Acrux sold off its royalty rights for Lenzetto under its existing licensing deal for $6.4 million. Royalty payments under its agreements were due to end in early 2026.
Acrux licensed Lenzetto to Gedeon Richter in 2016. Evamist for the US market was licensed in 2004 to Vivus, with commercial rights subsequently moving to KV Pharmaceuticals, Lumara Health and then Padagis (formerly Perrigo).
Future Focus for Acrux
Over the last decade Acrux focused on its topical generics portfolio with mixed success. Over the first three quarters of this financial year the company has generated $2 million of profit share and royalty income, which should be expected to continue over the medium term.
Acrux currently receives royalty and profit share income from four products: Nitroglycerine ointment, two strengths of Dapsone gel, and from Evamist. The rights to Pridocaine & Lidocaine cream were sold in December to the company's distributor for US$550,000.
At the end of March Acrux held $0.6 million in cash, with a placement conducted in April raising $1.6 million at $0.0095 per share. Its net cash burn for the financial year to the end of March was just $0.7 million, having received an R&D tax rebate during the year of $3 million.
Acrux has decided to reduce its work on the topic generics business, with an emphasis on its existing portfolio of generic products, and most importantly on the development of a topical testosterone product for women (see feature on HRT products below), to address low libido, which Warmbrunn describes as a 'generational opportunity' for the company. The company will also seek to expand the territories its existing generics are sold into.
Following changes by the FDA around hormone replacement therapies for women, Acrux has met with the FDA to discuss the regulatory path forward for this testosterone program.
Acrux is seeking to secure a co-development partner in coming months, aiming to become the first testosterone product for women approved by the FDA. It has an advantage in having already completed a Phase II study in women with testosterone therapy.
Acrux is capitalized at $6 million.
Bioshares recommendation: Speculative Buy Class C
FDA Expert Panel on HRT Use - "History Got it Wrong"
In July last year the FDA organised an expert panel review on hormone replacement therapy, chaired by the then FDA Commissioner Dr Marty Makary.
In 2002 the use of hormone replacement therapy (HRT) products plummeted following the Women's Health Initiative stopping a major clinical study showing that estrogen plus progestin carried unexpected risks. The following year the FDA placed a black box warning on all HRT products indicating that they increased the risk of breast cancer, stoke, heart disease and dementia. However in recent years the use of HRT products has been returning as new and more complete data highlights the benefits and displaces the earlier health risks associated with these products.
Dr Mary Jane Minkin said that 9 July 2002 is a day that everyone will remember, which is the day that "everyone threw their estrogen into the toilet', referring to the WHI opinion that supplemental estrogen increases the risk breast cancer along with elevating a number of other health risks. Dr Minkin said that not only did women stop taking estrogen at that point, but women stopped learning about estrogen. In 2013 Dr Wen Shen from Johns Hopkins did a survey of all the residency programs in the US and found that 80% were not teaching about menopause. Ten years later this had increased to just 30% of residency programs teaching about menopause.
Dr Heather Hirsch believes that "History has got it wrong when it comes to menopausal hormone therapy", and that "Women deserve current evidence and not outdated myths."
Latest Meta Data analysis
Looking at meta analysis data, Dr Howard Hodis summarised that when HRT is started at an age of less than 60 or within 10 years of menopause, there is a 50% reduction in heart disease, and a 30% reduction in all-cause mortality. When started after the age of 60 there is no benefit.
The data shows that all fractures and diabetes is reduced with HRT, Alzheimer's disease and dementia mortality in women who have been taking estrogen is significantly reduced when followed up after 18 years, all cancer deaths and all cause mortality are significantly reduced with HRT, and there is no increase in the incidence of colorectal or ovarian cancers with HRT.
"It is past time to stop overstating risks and promoting fear and confusion about hormone therapy which has been shown to safely offer life-enhancing and life-saving benefits for countless menopausal women."
Estrogen in the Brain the Master Regulator
Dr Philip Sarrel said that estrogen in the brain has been referred to as the master regulator. In one small study (78 subjects) women who began taking estrogen replacement experienced a drop in memory issues from 82% to 26% on average, and sleep disturbance fell from 80% to 10% after six months.
Two Thirds of People with Alzheimer's are Women
Brain heat generated from hot flushes causes vasodilation and inflammation in the brain leading to the early onset of neurodegenerative diseases. Hormone therapy is associated with a reduction in age-related neurodegenerative diseases. This includes a reduction in the incidence of Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, ALS and all-cause dementia, according to Dr Roberta Diaz Brinton. Of the people who develop Alzheimer's, two thirds are women. Dr Brinton believes that this disease starts earlier in women due to the menopausal transition.
Estrogen Can Reduce Incidence of Osteoporosis Bone Fracture by up to 50%
Orthopedic surgeon Dr Vonda Wright said that osteoporosis ends up affecting 40% of women over the age of 40, four times that which affects men, and occurring 10 years sooner than in men. In perimenopausal women, Dr Wright said there is a sharp precipitous drop in bone quality, with a 15%-20% drop around this five to seven year period. Dr Wright said that estrogen plays a key role in the remodelling of bone.
Estrogen is the only established interventional therapy that reduces the frequency of osteoporosis fracture by 30%-50% according to the NIH and the European foundation for osteoporosis and bone disease. Dr Vonda firmly believes the need for interventional surgery in women using metal implants can be prevented with estrogen therapy!
Benefits of Testosterone Therapy
Dr Kelly Casperson backed up this data stating that one in six American women will suffer a hip fracture in their lifetime. Dr Casperson said that following a hip fracture, 50% were less likely to need a cane or a walker when taking testosterone. However there is no FDA approved testosterone dose for women. All of the testosterone scripts Dr Casperson writes are for men. "The FDA is failing women by denying access to a hormone their bodies naturally produce (in the ovaries and adrenals)." Dr Casperson said that testosterone is not just for libido. "It's a neural hormone, critical for mitochondria, nerve function, muscle, bone and brain function. Libido improves because dopamine and blood flow in the brain improve.
Two female testosterone products had failed to gain FDA approval due to the lack of safety data, which Dr Casperson said is a legacy of the WHI backlash in 2002 around the safety or female hormone products. Dr Casperson said that women are forced to microdose using testosterone products produced for men at 10 times the dose needed for women. She has received feedback from women showing profound improvements in cognitive function when taking testosterone. Although it is not approved for women, almost as many women take testosterone in the US as men.
With respect to dementia, Dr Casperson said that higher testosterone levels correlated with less dementia. One in four women in the US are taking antidepressants despite the risk of bone loss and decreased libido. “New data shows more women can come off their SSRIs by adding testosterone than by just using estrogen alone." Only four countries - Australia, New Zealand, South Africa and the UK - have female approved testosterone, but women have to request it for low libido, which is a stigmatised issue.
Dr Casperson would like to see testosterone for women fast tracked in the US.
HRT Can prevent 50% of UTIs in Women
Dr Rachel Rubin said that menopause is a castration event and that without hormonal support, it never fixes itself. Dr Rubin said that not only do local vaginal hormones, such as estrogen and DHEA, help with sex, but they also help prevent 50% of urinary tract infections, a fact which has been known for decades, and can lead to urosepsis. However they have not been prescribed because of the black box warnings of stroke, blood clots and heart attacks placed on these products by the FDA in 2003 with no clinical evidence to support the warnings.
Summary
Former FDA Commissioner Makary said that for too long women's health issues had been sidelined and downplayed. He thanked the participants of the expert panel session by saying: "You are all giants in this field and we are learners and trying to listen."
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