Can this new endometriosis drug change therapy? What women need to know

A new experimental drug could eventually offer women with endometriosis — a painful condition in which tissue lining the uterus overgrows outside it to cause extreme pain, bleeding and fertility problems —- some relief. They may not need to rely on hormone pills, oral contraceptives or surgery.

The US (FDA) had cleared ENDO-205, a first-in-class, non-hormonal targeted peptide therapy for a Phase 1 clinical study in healthy premenopausal women of reproductive age. This drug works without suppressing reproductive hormones, is designed to target endometriosis lesions directly, raising the possibility of treating the disease while avoiding some of the hormonal effects associated with current medicines.

“In summary, it addresses endometriosis as a systemic inflammation disorder. So far it was considered a hormonal or period-only disease. Existing hormonal treatments, including combined oral contraceptives and progestins, work by modifying hormone signalling that affects fertility. ENDO-205 is being developed with a different proposed mechanism,” says Dr Anshumala Shukla-Kulkarni, head of Minimally Invasive Gynaecology and Gynaecology Laparoscopic and Robotic Surgery at Kokilaben Dhirubhai Ambani Hospital, Mumbai.

At this stage, researchers will primarily look at safety, tolerability, how the body processes the drug and appropriate dosing. Whether it actually treats endometriosis will have to be established through later trials.

What is ENDO-205?

ENDO-205 is a peptide — a short chain of amino acids that can interact with cells and tissues. The peptide is designed to remain inactive in normal, neutral tissue but become activated in the more acidic environment associated with endometriosis lesions. Once activated, it enters abnormal endometriosis cells and triggers their destruction.

As Dr Kulkarni explains, “In normal neutral tissues it is inactive. When inflammation rises, the pH drops to acidic levels, which activates the peptide.”

What does ‘non-hormonal’ mean?

Most established medical treatments for endometriosis work, at least partly, by modifying hormonal signalling or reducing the effects of reproductive hormones. A non-hormonal treatment aims to act directly on the disease process instead.

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That could eventually matter for women who need treatment while wanting to preserve reproductive function. But it is too early to conclude that ENDO-205 will preserve ovarian function, menstrual cycles or fertility. Those outcomes will need to be assessed in clinical trials.

Could ENDO-205 reduce endometriosis pain?

Not necessarily. Endometriosis pain is complex and can involve inflammation, nerve changes, adhesions and damage to affected organs. “If the lesions regress, there could be an improvement in symptoms, but pain in endometriosis is multifactorial. So, it is difficult to say at this stage whether it will stop pain,” Dr Kulkarni says.

The makers have reported encouraging preclinical findings involving lesion targeting and reduction. However, laboratory and animal results cannot establish whether ENDO-205 will reduce pain or improve quality of life in people with endometriosis.

What will the clinical trials need to show?

The planned Phase 1 study in healthy premenopausal women will primarily assess safety, tolerability and appropriate dosing. It is not designed to prove that ENDO-205 treats endometriosis.

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Later studies involving people with the disease will need to determine whether it reduces lesions, pain or disease progression, how long any benefit lasts and whether lesions recur. Researchers will also need to examine ovarian function, ovulation, fertility and pregnancy outcomes.

Could it replace hormonal treatment or surgery?

If future trials demonstrate that the drug is safe and effective, it could potentially become another treatment option, and researchers could then investigate whether it reduces the need for other treatments.

Dr Kulkarni says such an approach could be particularly significant if endometriosis is identified and treated before substantial organ damage occurs. “It could potentially replace hormonal medication and surgery, especially if given in the early stages before organ damage, if the human trials demonstrate that it is safe and effective,” she adds.

Will the drug be available in India?

If the drug eventually proves safe and effective in human trials and its developers seek approval in India, it would have to undergo the applicable Indian regulatory process, including requirements of the Central Drugs Standard Control Organisation (CDSCO). “It is a long wait, but it is a great start to think beyond hormones and treat endometriosis as an inflammatory disease,” Dr Kulkarni said.