Myovant’s relugolix clears first uterine fibroids PhIII test, but competition from AbbVie/Neurocrine makes investors jittery

Vivek Ramaswamy’s bet on Takeda’s relugolix has worked — sort of.

Vivek Ramaswamy

Less than three years after the prolific dealmaker spawned Myovant as part of his umbrella of ‘Vants’ with a record $218 million IPO, the treatment in-licensed from the Japanese drugmaker passed muster in a late-stage study in women with uterine fibroids, which are common non-cancerous female reproductive tract tumors. But investors were not quite as impressed as the company’s shares $MYOV tumbled in early Tuesday trading.

The oral drug, which is an antagonist of the gonadotropin-releasing hormone (GnRH) receptor, is designed to suppress estrogen production in women. It is being tested in twin pivotal studies involving women with uterine fibroids and heavy menstrual bleeding, called LIBERTY 1 and LIBERTY 2.

Myovant on Tuesday unveiled the results of the first Phase III trial, which enrolled 388 women and tested relugolix (40 mg) in combination with female hormones estradiol (1 mg) and norethindrone acetate (0.5 mg). In the trial, patients received either relugolix combination therapy for 24 weeks; relugolix monotherapy for 12 weeks followed by relugolix combination therapy for the next 12 weeks; or placebo once daily for 24 weeks.

In the study, 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo (p < 0.0001) — meeting the main goal. A response was defined as a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction from baseline in menstrual blood loss volume during the last 35 days of the 24-week treatment period. On average, women receiving relugolix combination therapy also experienced an 84.3% reduction in menstrual blood loss from baseline, which was a key secondary endpoint.

AbbVie $ABBV and Neurocrine Biosciences’ $NBIX therapy elagolix (branded as Orilissa), which was approved last year to treat endometriosis, is also being evaluated for use in uterine fibroids. It is has a similar mechanism of action compared to relugolix but is taken twice-daily. The companies have reported data from two pivotal six-month studies. In one late-stage study, 68.5% (p<0.001) of elagolix-treated women with uterine fibroids achieved clinical response compared to placebo (8.7%), in the second trial 76.2% (p<0.001) of elagolix-treated women with uterine fibroids achieved clinical response compared to placebo (10.1%). A regulatory submission for elagolix in uterine fibroids is anticipated in mid-2019.

Phil Nadeau

“Relugolix will follow Neurocrine’s GnRH antagonist Orilissa to the U.S. market. However, relugolix has certain differentiating features (once-daily dosing, full estrogen suppression) that should allow it to capture share, particularly in situations such as uterine fibroids or severe endometriosis where high GnRH suppression is necessary,” Cowen’s Phil Nadeau wrote in a note in February, estimating that in 2025 relugolix will generate $1.15 billion in uterine fibroid sales.

ObsEva $OBSV is also currently developing a GnRH receptor antagonist called Linzagolix for uterine fibroids — data from its late-stage study is expected in the fourth quarter of this year.

“(G)ynecologists reinforced our thesis that the clinical profile of the GnRH antagonists could address a significant unmet need in uterine fibroids and endometriosis, and that given the heterogeneity in patient response, there is likely to be a demand for all the three GnRHs”, SVB Leerink analysts wrote in a note published last month.

Data from LIBERTY 2 is expected in the third quarter of 2019, and if positive, the two trials will form the basis of a marketing application that is planned for the fourth quarter, Myovant said.

Myovant’s investors are not quite as enthusiastic. AbbVie (our Goliath) will file its marketing application in the coming months, and if approved will have some time to establish itself before Myovant (our David) makes it to the market, by which time it will be much harder for the smaller player to take a bite out of AbbVie’s market share. Myovant’s stock $MYOV was down about 29% at $12.22 in morning trading.

Baird’s Brian Skorney issued a glowing review of the Myovant data. “The first Phase 3 data set in uterine fibroids hit all the check boxes for an approvable, competitive program. We think the stock free-fall reflects a sell-the-news dynamic, exacerbated by an absence of efficacy differentiation and financing concerns. We are buyers on the dip and continue to believe relugolix has blockbuster potential in uterine fibroids and endometriosis,” he said in note on Tuesday.

“But I think the overarching pressure on the stock is due to the financing needs ahead of a launch that is probably ~2 years away,” he added in an email to Endpoints News.

Uterine fibroids are almost always benign tumors that emerge in or on the muscular walls of the uterus. They can cause symptoms such as abnormal uterine bleeding, heavy or painful periods, anemia, abdominal pain, backache, increased abdominal girth and bloating, urinary frequency or retention, constipation or painful defecation, pregnancy loss, painful intercourse and, in some cases, infertility. Between 20% to 80% of women develop fibroids by the time they reach age 50, according to HHS estimates.

Lynn Seely

Takeda $TAK has an equity stake in Myovant, which is also evaluating relugolix as a treatment for endometriosis in women, as well as advanced prostate cancer in men. The biotech is run by Lynn Seely, the former CMO of Medivation.

The infectious former hedge fund manager Ramaswamy has whipped up a plethora of companies under his umbrella firm Roivant, by convincing investors that lucrative returns can be made by taking experimental drugs gathering dust on big pharma shelves all the way across the finish line. His first big bet on Alzheimer’s/dementia assets — much like everything else in the battered field — failed spectacularly at his seminal Axovant $AXON}, but he has reinvigorated the company into a gene-therapy player. Meanwhile, his enthusiasm for the strategy has not withered, as he has birthed various other ‘Vants’ focusing on different illnesses and therapeutic approaches.

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