What exactly is Sepranolone?Sepranolone (UC1010) is an endogenous compound occurring naturally in the brain. Sepranolone inhibits the effects of allopregnanolone, the steroid that causes PMDD. Its effects have been demonstrated in animal models of PMDD, and in a clinical pharmaco-dynamic model that evaluated how a new family of compounds influences the GABA mechanisms in the brain. These compounds are called GAMSAs – GABA-A Modulating Steroid Antagonists. Sepranolone is a GAMSA.
How does it work?Sepranolone inhibits the effects of the GABA steroid allopregnanolone on a GABA-A receptor in the brain. This prevents PMDD symptoms from emerging. Sepranolone is highly specific, only inhibiting the effect of GABA steroid action on the receptor. It does not influence the effects of any other active GABA-A receptor substances either. This high specificity means it has very low risk of side-effects.
What tests have been carried out so far and how successful were they?A Phase IIA study tested 120 women with PMDD to evaluate the safety, efficacy and pharmacokinetics of Sepranolone. It was a double-blind, randomized, placebo-controlled, clinical trial. It showed that Sepranolone alleviated PMDD symptoms, normalized work and family life, and was safe and well tolerated. Sepranolone achieved 80% symptom reduction in the tests, well over double that of a typical placebo response. Phase IIB trials are currently running in the UK, Poland, Sweden and Germany, and will involve 250 women.
THE SEPRANOLONE STORY
Sepranolone – built on over 40 years’ world-leading research.
Research that helped overturn decades of prejudice and misconception.
Yet it all started in 1972… Before “PMDD” even existed…
Listen to the story
Volunteer medical student Torbjörn Bäckström begins helping a young woman in the psychiatric unit he works at. She’s repeatedly sectioned by Police for violent behaviour—yet her symptoms always vanish the moment her period arrives.
Bäckström begins PhD research into the effects of reproductive hormones at the physiology department of Umeå University.
Working with patients with menstrual epilepsy, Bäckström becomes the first researcher in Sweden to measure the brain’s active GABA-A modulating steroids in PMS patients. He discovers that menstrual epileptic seizures peak in correlation with changes in GABA-A modulating steroids.
Bäckström’s research confirms that, despite the general scientific consensus that active GABA-A modulating steroids reduce anxiety, for some the steroids have a paradoxical effect—producing anger, anxiety and aggression. The number of patients with this paradoxical effect correlate with the number with severe PMS and PMDD.
Research starts into discovering and developing natural compounds in the brain that can modulate and inhibit the effects of GABA-A modulating steroids. These antagonist compounds are eventually named GAMSAs (GABA-A modulating steroid antagonists).
Torbjörn Bäckström starts to look in earnest for natural antagonists to allopregnanolone, the GABA-A modulating steroid that PMDD sufferers have a heightened sensitivity to.
An endogenous, naturally occurring compound is identified that is a proven antagonist to allopregnanolone. In 1998 it is patented and begins development as a therapy. Today, it is called Sepranolone.
The company “Umecrine Mood AB” is founded by Professor Bäckström to develop Sepranolone, the world’s first dedicated treatment for PMDD.
The Phase I study of Sepranolone shows early the safety of the compound
The Phase IIA study shows significant therapeutic benefit of Sepranolone, reducing PMDD symptoms by 80%.
Phase IIB study ongoing in four countries—Sweden, Poland, Germany and the UK.
Sepranolone is released as the world’s first dedicated treatment for PMDD, helping women worldwide remain in control of their lives.
ALLOPREGNANOLONE: A potent neurosteroid that impacts us all
Sex hormones are pivotal in Menstrual Migraine and PMDD, in particular the female sex hormone Progesterone. It produces a powerful GABAA receptor neurosteroid in the brain’s emotional center, the amygdala, called Allopregnanolone.
For women of a fertile age the intensity and frequency of migraine attacks is commonly concentrated just prior to and during menstruation, when the concentration of Allopregnanolone is dropping rapidly. For some women this sudden drop in concentration produces highly painful ‘withdrawal’ symptoms, in the form of sudden, severe migraine attacks—Menstrual Migraine.
Sepranolone is the natural, endogenous compound that the brain produces to modulate the effects of these fluctuations in allopregnanolone.
SEPRANOLONE: MARKET POTENTIAL
Asarina Pharma is developing Sepranolone as a unique, first-in-class therapy that will meet today’s substantial, unmet need for an effective, dedicated treatment for PMDD.
A dedicated partner
With clinical proof-of-concept for Sepranolone, we seek to partner the program with a dedicated pharma partner searching for novel opportunities within Women’s Health.
It is important for the market success of Sepranolone that a partner is part of the planning and execution of the pivotal clinical studies, as well as taking charge of the regulatory process: to ensure as fast and efficient market entry as possible.
2nd generation sepranalone
Asarina Pharma has a 2nd generation, small molecule, a Sepranolone analogue for oral administration in preclinical development.
Severe, debilitating and widespread—PMDD remains one of the most untreated conditions in the world.
TARGET POP’ US: 4 MILLION (approx.)
TARGET POP’ EUROPE: 6 MILLION (approx)
According to a recent patient survey, up to 80% of women with PMDD or severe PMS are not diagnosed nor their condition recognized by a physician. PMDD remains severely under-diagnosed, and under-treated due to lack of effective drugs on the market..
‘MODERATE EFFICACY’, SERIOUS SIDE EFFECTS: TODAY’S TREATMENTS FOR PMDD
There are currently no products specifically developed to treat PMDD. Patients are most often prescribed anti-depressants (SSRI’s) or oral contraceptives (OC) for symptom relief. These treatments only give symptom relief in some PMDD patients and are often associated with unacceptable side effects.
PMDD in the US: TAPPING THE POTENTIAL
The US is a key target market for Sepranolone. In the US PMDD is a well-established diagnosis described in DSM-5 (the Diagnostic and Statistical manual of Mental Disorders).
50% of PMDD sufferers in the US do not currently seek treatment 25% of sufferers who’ve been offered treatment remain non-responsive to it.
SETTING AFFORDABLE TREATMENT WILL DRIVE MAJOR REVENUES
Setting PMDD treatment with Sepranolone at 450 USD per month would present no major barrier to access for users. Initially Sepranolone will be prescribed as a second-line treatment to those 25% of PMDD patients who have failed to respond to SSRIs or OCs. Even with treatment competitively priced at 450 USD, and based on the most conservative estimates of refractory patients, peak revenues of 230 MUSD can be expected. Non-risk adjusted gross revenues of 780 MUSD can be expected when basing uptake on more realistic patient number estimates, such as the number of patient applications in our Phase IIB clinical studies.