Neurocrine wastes no time delivering deal but hurdles remain

Neurocrine Biosciences is certainly on a roll. A mere three weeks after announcing positive phase IIb data on endometriosis agent elagolix the company has delivered a lucrative partnering deal with Abbott Laboratories, complete with a chunky $75m upfront signing on fee (Positive endometriosis data could be start of Neurocrine resurrection, May 27, 2010).

This is certainly encouraging for drugs in this class, gonadotropin-releasing hormone (GnRH) antagonists, which undoubtably have a patchy development history; even Neurocrine has travelled a bumpy road to get to this stage (Neurocrine punished for uncertainty as phase II data rolls in, March 26, 2009). However, as the owner of Lupron, an $800m-a-year GnRH analogue already on the market for endometriosis, Abbott makes for a logical and motivated partner and no doubt late-stage trials will commence quickly.

First-in-class

Elagolix is described as a first-in-class oral GnRH antagonist. It works by blocking GnRH receptors in the pituitary gland, ultimately reducing circulating sex hormone levels. However, because elagolix only partially suppresses oestrogens, maintaining the main sex hormone oestradiol in the low-normal range, the companies hope that symptoms of conditions such as endometriosis can be reduced while side effects often associated with excessive suppression of estrogens, such as bone loss, are avoided.

Results from the phase IIb trial called Daisy Petal announced last month revealed a significant reduction in pain amongst endometriosis sufferers. Abbott also plans to study the drug further in uterine fibroids, benign tumours that form on the wall of the uterus that can cause heavy menstrual bleeding, pain and nausea. Symptoms can also include miscarriages and infertility and treatment sometimes requires surgery.

The deal sees Abbott gain worldwide rights to develop and commercialise elagolix and all next-generation GnRH antagonists developed by Neurocrine, for both women and men. As well as the upfront fee Abbott will fund all ongoing development and pay milestones of up to $500m plus royalties on sales.

Follow on

Abbott no doubt sees this as a follow-on candidate for Lupron, an injected drug sold to treat prostrate cancer, endometriosis, early puberty and uterine fibroids.

Although the composition of matter patent protecting Lupron expired in 1996 usage patents do not end until 2014 in the US. Analysts see sales booked by Abbott declining from this year, from $777m to $278m by 2016, according to EvaluatePharma,so the company will be motivated to push elagolix forward quickly.

Last year GnRH agonists like Lupron, which also includes AstraZeneca’s Zoladex and Sanofi-Aventis’ Eligard, generated sales of $3.41bn. However while they are established and successful drugs, the antagonists coming up behind still have to prove themselves.

Less successful

A couple of agents, Merck & Co’s Orgalutran and Merck KGaA’s Cetrotide, have already made it the market to treat female infertility but both are very small products and importantly are still injected.

Others have been less successful. Æterna Zentaris appears to be winding down work on cetrorelix, which generated disappointing data in benign prostatic hyperplasia (BPH) last year, resulting in partner Sanofi-Aventis handing the rights back six months later. An analysis by EP Vantage at the time revealed how the class was struggling to progress (Æterna sinks on BPH data; questions LHRH antagonists, August 18, 2009).

Earlier this year Spectrum Pharmaceuticals ended work on its candidate ozarelix in BPH after generating mixed data; the company also pointed to the cetrorelix failure in its decision.

Significant hurdles

As such, despite a couple of stumbles elagolix appears to be leading the pack now; being the first to crack oral administration has no doubt boosted its appeal. In afternoon trading shares in the company had leapt 14% to $5.36.

Still, indications such as BPH have yet to reach later stage trials, and proved to be the downfall for other candidates. So while Neurocrine deserves to be applauded for today’s deal and having $75m in the bank is without doubt a boon, caution is still advisable.

Phase III clinical success is the next and possibly most significant hurdle for elagolix.