Upcoming events: Edoxaban faces panel and elagolix endometriosis data

Welcome to your weekly digest of approaching regulatory and clinical readouts. Daiichi Sankyo is expecting to hear from an advisory panel on October 30 for its factor Xa inhibitor edoxaban in stroke prevention, and with the patent loss of its once-blockbuster looming it needs a full pass to begin to plug the revenue hole.

Meanwhile before the end of the year data are expected from the first phase III trial of Neurocrine and AbbVie’s elagolix. This is being tested in endometriosis-associated pain, and results are largely expected to follow earlier positive trials and could bring renewed pipeline attention to the project.

Daiichi Sankyo: edoxaban

Lixiana, as edoxaban is known in Japan, was approved there in 2011 for the prevention of venous thromboembolism after major orthopaedic surgery. Last month it received expanded approval for the prevention of ischaemic stroke and systemic embolism in patients with non-valvular atrial fibrillation.

The stroke indication represents the biggest potential market and will be the topic of the upcoming US adcom. A final approval decision is expected early next year, and edoxaban is also filed in Europe, where a decision is expected at the end of the year or early 2015. The product has the proposed US trade name Savaysa.

The panel meeting will discuss the results of the 21,000-patient Engage AF-Timi 48 trial. At AHA last year the once-daily pill matched mainstay warfarin in preventing stroke while reducing the risk of major bleeding incidents (AHA – Lixiana measures up to stroke prevention competitors, November 20, 2013).

However, it failed to significantly reduce the risk of death from cardiovascular causes or a separate composite measurement of CV events. Of the novel, oral anti-coagulants, Eliquis has only managed to demonstrate a reduction in the risk of death.

The regulators will also pay close attention to the fact that the risk of ischaemic stroke was increased by 41% at 30mg; this was balanced by a two-thirds reduction in the risk of haemorrhagic stroke.

Worldwide 2020 consensus forecasts for edoxaban are $880m, according to EvaluatePharma. It could become Daiichi's biggest growth driver, helping to replace the hypertension pill Benicar, which loses patent protection in 2016.

However, edoxaban will be the fourth oral anti-coagulant to reach the market. Xarelto is forecast to be the best-selling factor Xa inhibitor by 2020 with $7.3bn in sales according to EvaluatePharma, with Eliquis in second place at nearly $4bn.

With difficult champions to beat, and without proving superiority to currently marketed products, edoxaban will have a tough time.

Neurocrine/AbbVie: elagolix

The Violet Petal trial enrolled 875 premenopausal women between 18 and 49 years old. Elagolix is being tested for the management of moderate to severe endometriosis-associated pain, and the co-primary endpoints are a responder analysis of dysmenorrhea (menstrual pain) and non-menstrual pelvic pain after three months of therapy. 

The women are followed for another three months and then all enter a six-month open-label phase. AbbVie is expected to release topline results once the six-month, blinded phase has been completed.

Endometriosis is a chronic condition that occurs when endometrial cells lining the womb migrate to other parts of the body. It causes painful or heavy periods, pain in the lower abdomen, pelvis or lower back, as well as fertility problems. Current treatments aim to reduce the severity of symptoms by pain medication, hormone treatments or surgery to remove endometriosis tissue.

A phase II trial called Daisy Petal enrolled 137 women, and the dysmenorrhea and non-menstrual pain responder rates were hit with statistical significance versus placebo. A second phase III called Solstice will read out late next year, while results from a phase IIb study in uterine fibroids are due in the middle of next year.

Stepping up

According to consensus data from EvaluatePharma, sales are forecast to hit $484m in 2020. However the range is wide, from $250m to $775m. Neurocrine gets worldwide royalties, with $167m forecast.

Abbott and Neurocrine signed a collaboration to develop and commercialise elagolix back in 2010. Neurocrine received $75m up front and is eligible to receive additional milestone payments of approximately $500m.

Neurocrine's most high-profile asset is the now wholly owned tardive dyskinesia project NBI-98854. Shares rocketed nearly 90% at the start of the year on positive data (Video replay brings Neurocrine back into the game, January 8, 2014).

However, elagolix data are expected to be positive so attention could turn back to the endometriosis agent.

Project Study Trial ID
Edoxaban Engage AF-Timi 48 NCT00781391
Elagolix Daisy Petal
Violet Petal
Solstice
Phase IIb uterine fibroids trial
NCT00973973
NCT01620528
NCT01931670
NCT01817530

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @JoEPVantage on Twitter

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