Just recently, Neurocrine Bio (NBIX) presented results from the full twelve month analysis of the Petal-603 study, which includes data from the six months on treatment and six months follow-up period. Petal was a phase IIb program that enrolled 252 women with confirmed diagnosis of endometriosis, and tested 150mg of Neurocrine’s gonadotropin-releasing hormone (GnRH), elagolix, in two cohorts (150mg QD or 75mg BID) vs. a control.

Results from the 150mg QD cohort were superior. Key findings from the 150mg QD program were with respect to:

  • Bone Safety – demonstrated no apparent effect after the first 24 weeks of treatment, or no cumulative effect on bone mineral density (BMD) after the full 48 weeks. Mean change from baseline for the elagolix 150mg QD remained close to the 0% mark at week 48, with n-telopeptide values within the normal range of between 6 and 19 nM BCE for the tested age group.
  • Pain Reduction – demonstrated a sustained improvement at week 48 compared to baseline in the Composite Pelvic Signs and Symptoms Score (CPSSS), with similar results on the ITT (n=252) and completers (n=131) analysis. Sub-components of the CPSSS demonstrate a “responder rate” on dysmenorrhea (heavy menstrual bleeding) of 77% at week 24 and 64% at week 48, and on non-menstrual pelvic pain were 86% at week 24 and 67% at week 48 (both p
  • Quality of Life – based on the Endometriosis Health Profile (EHP-5) scale, which assessed the impact of endometriosis symptoms on five core domains, improved from baseline 80% of subjects reported that they suffered difficulties across all domains “sometimes,” “often” or “always” to 60-80% of subjects saying “never” or “rarely” to these same EHP-5 questions at week 48.
  • Safety and Tolerability – demonstrated adverse events that were generally mild and transient in nature, and included things such as headache and nausea.No serious adverse events, including no pattern of excessive estradiol suppression, were observed at a rate that would prohibit future development of the candidate.         

Neurocrine management has been active in presenting this data above, most recently at the 91st Annual Meeting of the Endocrine Society (ENDO) in June 2009. We expect more data to come. Neurocrine should release the six-month data from the Lilac-702 program shortly. This data should give us a better sense of durability of effect, additional safety information, DXA scan data and a more detailed analysis of the multiple endpoints.

In October 2009, management should released data from the Tulip-703 program. This trial has a similar design to the Lilac-702 program, only with an active comparator in leuprolide depot (Abbott’s [ABT] Lupron).

In the meantime, management will hold an end-of-phase II meeting with the FDA to take place in the fourth quarter 2009. Management has been meeting with outside consultants to better understand the statistical “floor effect” observed in the Lilac-702 study with the daily assessments of non-menstrual pelvic pain.

At that FDA meeting, management and the FDA will outline a pivotal phase III program for elagolix. We expect that the pivotal phase III program will include two large-scale (n~500) patient programs with some modified NRS / NMPP / DYS endpoint. There will also be a long-term (n~400) safety program, and a head-to-head non-inferiority program vs. Lupron for the European submission.

Neurocrine may seek a special protocol assessment (SPA) for the phase III trials. The company may also conduct one additional phase II program prior to the phase III trials depending on what endpoint is agreed upon for the phase III. Nevertheless, management believes the phase III trials should start during the first half of 2010. In the meantime, management remains in late-stage discussions with potential partners for elagolix.

Management continues to mention that they are in late-stage talks with interested parties about partnering the drug for future development and commercialization. That being said, we still don’t think they sign a deal until after the Tulip-703 data comes out later this year. We think partners will want to see the full six month data from the entire phase II program before they sign.

Also, the potential exists that partners may want to wait until after the end-of-phase II meeting with the FDA in the fourth quarter 2009 so they have a better idea of what’s in store — in terms of costs and achievability — for the phase III program.

Nevertheless, we believe elagolix is a highly attractive molecule and a lucrative partnership will eventually be secured prior to the phase III initiations in 2010.

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