Endometriosis: How biotech is pioneering new patient options

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Endometriosis, an under-researched condition, has been rather difficult to treat with no cures to date. It is caused by the growth of tissue – similar to those in the uterine lining – outside the uterus, leading to debilitating pelvic pain during sex and heavy periods. 

Around 190 million women and girls have been diagnosed with endometriosis across the world, according to the World Health Organization (WHO), and although the disease affects one in 10 women as well as trans men and nonbinary people who menstruate, therapeutic research has often been ignored.

As 50% of endometriosis patients deal with fertility issues, the economic cost that the condition has on the U.S. alone – both in terms of medical care and lost productivity – is estimated to be around $78-120 billion annually, according to Bruce Nicholson, chief scientific officer (CSO) and co-founder of Hera Biotech, a U.S.-based women’s health company that is developing endometriosis diagnosis tests.

Nicholson explained that despite this pervasive challenge to women’s health, patients suffer an average delay of 8 years for diagnosis, which can only be done reliably with surgery. 

While hormonal therapy can help alleviate symptoms, it fails to address infertility. Moreover, the surgical removal of lesions is often temporary as the lesions return 50% of the time, according to Nicholson.

“A major reason why we do not yet have better options has been the chronic underfunding of research in this area. Similarly common diseases, like diabetes and breast cancer (affecting 12-15% of the population) receive 15 and 30-fold greater levels of funding from the NIH, respectively. Rarer and similarly non-lethal diseases like Crohn’s disease, receive 65-old more funding per patient,” said Nicholson.

“Despite these limitations, we have seen some significant progress in the study of endometriosis over the last 5-10 years.”

As uncovering the complexity of the gut microbiome has been crucial to healing inflammatory diseases, an intriguing link between the microflora and endometriosis could look into potential drug targets to treat the condition.

“Real therapeutics to interrupt or prevent the disease itself will require much more extensive studies on the cellular pathophysiology underlying lesion formation, and the signaling pathways that lead to disease progression. This is the strategy that has led to great recent advances in cancer research but this will take a concerted change in research funding for endometriosis to match the extent and severity of this disease,” said Nicholson.

Presently, with clinical trials showing promise and with the discovery of new drug targets, there is hope for endometriosis care. Let us take a look at some of the recent advancements in endometriosis research.

Table of contents

    Repurposed cancer drug in phase 2 endometriosis trial  

    While treatment for endometriosis depends on factors like age and the extent of the symptoms, surgery and hormone treatment are typically the only options. And the fact that there hasn’t been a new treatment in 40 years, expresses how difficult-to-treat the disease can be. But now, that’s all about to change. 

    The drug dichloroacetate holds therapeutic promise. Typically used to treat metabolic diseases in children and tested as a cancer drug previously, it is being repurposed and could prove to be effective against endometriosis symptoms. 

    People with the condition tend to produce excessive amounts of a harmful chemical called lactate – a byproduct of metabolic reactions in the body – which leads to the development of endometriosis cells. Dichloroacetate has been found to reduce lactate levels and control the spread of abnormal cells.

    The researchers at the University of Edinburgh in Scotland had also tested the drug on a mouse model, which exhibited lower levels of lactate and lesions that had shrunk after seven days.

    “Endometriosis can be a life-changing condition for so many women. Now that we understand better the metabolism of the cells in women that have endometriosis, we can work to develop a non-hormonal treatment. Through a clinical trial with dichloroacetate we should be able to see if the conditions we observed in the lab are replicated in women,” said Andrew Horne, Lead Researcher from ​​​​​the MRC Centre for Reproductive Health at the University of Edinburgh.

    As the drug was expected to go into phase 2 in spring, if successful in the clinic, the drug could eventually be prescribed by the U.K. National Health Service (NHS), marking a major win for the endometriosis community.

    Endometriosis clinical trial in South Korea meets endpoint 

    A clinical trial testing a drug to treat endometriosis hit its endpoint in May. South Korean biotech Tiumbio’s merigolix was given to patients with moderate to severe endometriosis-related pain. The drug is a gonadotropin-releasing hormone (GnRH) antagonist, which is a class of medicines that is used to block the production of sex hormones. 

    The primary endpoint of the study was to relieve menstrual pain (dysmenorrhea), which it met in 12 weeks. The 86 patients who enrolled were separated into different cohorts and received varying doses of the drug – 120 mg, 240 mg, and 320 mg – and the placebo. 

    The drug was found to be “statistically significant and clinically meaningful.” The dysmenorrhea scores were -4.3 for the 120 mg dose, -5.4 for the 240 mg dose, and -6.2 for the 320 mg dose, while the placebo group reported -2.7. These scores indicate that the drug improved the condition in patients as zero is associated with no pain, one to three means mild pain, four to seven is for moderate pain, and eight to 12 implies severe pain.

    Some of the side effects recorded were hot flushes, headache, and nausea.

    The drug also gives hope to treat people who have uterine fibroids, which are non-cancerous growths that develop in the uterus.

    Diagnostic tool gets fast tracked by FDA in clinic

    A type of endometriosis called superficial peritoneal endometriosis forms as a shallow lesion along the membrane that lines the abdominal cavity called the peritoneum. As the lesions tend to be quite small, they are not well-detected in ultrasound and MRI, and the gold standard is considered to be laparoscopy, which is invasive. But the U.S. FDA has granted Fast Track Designation to the diagnostic tool maraciclatide to be able to detect the disease, a step forward towards broadening options for people.

    British radiopharmaceutical Serac Healthcare’s 99mTc-maraciclatide is a radio-labeled tracer, which binds to the cell-adhesion molecule αvβ3 integrin. In endometriosis, these molecules are abundant when blood vessels are formed.

    “Granting Fast Track designation to maraciclatide highlights the FDA’s recognition of the critical need for improved diagnosis of endometriosis,” David Hail, chief executive officer of Serac Healthcare. “A non-invasive test which could be used for earlier diagnosis of endometriosis would represent a major advance in women’s healthcare.”

    The tool has been tested for breast cancer and bone metastases – a condition where cancer cells spread from their original site to a bone – and is currently in the clinic for rheumatoid arthritis.

    New research explores cannabis as a treatment for endometriosis

    Medical cannabis has been studied for its anti-inflammatory properties and is used to alleviate side effects caused by chemotherapy, and has been prescribed for treating epilepsy and multiple sclerosis. A clinical trial by the Western Sydney University in Australia was announced last year to investigate its potential benefits for the treatment of endometriosis.

    The research, for which the university will receive $660,000 from the Wilson Foundation, will look into the effect of cannabis on the cell-signaling endocannabinoid system (ECS), as well as inflammatory markers. The double-blind randomized controlled trial will evaluate whether medicinal cannabis – in the form of cannabidiol (CBD) isolate or a balanced oil containing both CBD and delta-9-tetrahydrocannabinol (THC) – can counter symptoms like pain caused by endometriosis against a placebo.

    As 59% of people who used cannabis for endometriosis-related pain relief reported that they do not rely on painkillers anymore, the trial is based on evidence from an earlier study that revealed that cannabis can regulate inflammation and immune function, through interaction with the ECS. 

    “Various phytochemicals, mainly CBD, from cannabis have well described analgesic, anti-inflammatory, and antidepressant actions, and can also reduce anxiety and nausea. Cannabis use in other chronic pain conditions has resulted in a “substitution effect” of pharmaceuticals, commonly opioid analgesics, by cannabis,” said Mike Armour, principal investigator of the study, and associate professor at NICM Health Research Institute at Western Sydney University, who explained that people in Australia who have taken cannabis to deal with the condition’s symptoms found that it improved sleep and gastrointestinal functions.

    “However, there is still a lot we don’t know about how or why cannabis may affect endometriosis symptoms and possibly slow lesion progression. The trial will allow us to determine the effective dosage range, ideal THC to CBD ratio, duration of treatment and so forth,” said Armour.

    Harnessing the target potential of the ECS – which after the brain, the female reproductive system has the most endocannabinoid receptors – Israel-based startup Gynica is developing a cannabinoid-based therapy for treating symptoms of endometriosis like chronic menstrual pain and painful intercourse. Studies for the therapy are ongoing.

    Drug candidate for endometriosis shows higher efficacy than current treatment in animal studies 

    The discovery of an overexpressed protein on endometriotic cells by the Basel-based startup Fimmcyte last year could mean more treatments are on the way.

    This observed overexpression, wherein otherwise has low expression on the lining of the uterus and the rest of the body, has paved the way for a possible drug target, one that is currently being explored by Fimmcyte. The company is developing a highly specific antibody that labels the endometriosis cells for clearance by the immune system, according to Mohaned Shilaih, co-founder of FimmCyte.

    The young biotech performed several studies on mice where patient-derived material was implanted, and it was found that the treatment was “highly effective and reduced the disease burden,” according to Shilaih. Not only did the therapy demonstrate efficacy that was higher than treatment with gonadotropin-releasing hormone (GnRH) antagonist, which is the current standard of care, but it also did not affect the hormonal balance, cycle, and ovarian weight in the mice.

    Shilaih said: “Endometriosis affects one in 10 women globally, with more than 30% reporting dissatisfaction with hormonal and/or surgical interventions due to the side effects and lack of efficacy. FimmCyte’s treatment will provide a much-needed non-hormonal therapy for women with endometriosis that could be safe and effective without undesirable side effects.”

    The company aims to continue research into its therapy for endometriosis and acquire funding for Investigational New Drug / Clinical Trial Authorization (IND/CTA) enabling studies, and hopes to begin clinical trials in 2025.

    As inflammation has been known to trigger endometriosis-related cell proliferation, research has found that the condition may be linked to other inflammatory as well as pain-inducing diseases.

    “Several labs around the world have collaborated in genome-wide sequencing studies to identify variants associated with endometriosis. This study mainly identified changes in later stage endometriosis associated with pain and inflammation, both consequences, but not causes of, endometriosis,” said Nicholson.

    The collaborative study by U.S.-based biotech Celmatix and genomics company 23andMe along with other researchers, was a genome-wide association study meta-analysis of 60,674 cases and 701,926 controls of people of European and East Asian descent. 42 genome-wide significant loci comprising 49 distinct association signals were identified which explained up to 5.01% of disease variance and methylation of genes in endometrium and blood, many of which were associated with pain perception, according to the study. 

    The research found that endometriosis may be linked to 11 conditions including migraine, back and multisite chronic pain (MCP), and inflammatory conditions like asthma and osteoarthritis.

    Further research could explore potential drug targets, which could expedite interventions for not just endometriosis but other chronic pain-inducing conditions as well.

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