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NBIX: Will File an NDA for Opicapone in 1H19

02/16/2018
By David Bautz, PhD

NASDAQ:NBIX

Business Update


Opicapone NDA to be Filed in 1H19

On Feb. 14, 2018, Neurocrine Biosciences, Inc. (NASDAQ:NBIX) announced the company will file a new drug application (NDA) for opicapone in the first half of 2019 following receipt of the meeting minutes from the January 2018 meeting with the FDA. During that meeting, the FDA did not request that Neurocrine conduct an additional Phase 3 study for opicapone prior to filing the NDA. We model for peak revenues of opicapone in the U.S. of approximately $150 million.  

Opicapone is a peripherally-acting and highly selective inhibitor of catechol-o-methyltransferase (COMT) to be used as an adjunct therapy to levodopa/DOPA decarboxylase inhibitors in patients with Parkinson’s disease (PD). It decreases the conversion of levodopa into 3-O-methyldopa, thus reducing the “off-time” period and increasing the “on-time” period of Parkinson’s patients.  

Opicapone is a third-generation COMT inhibitor with a highly favorable pharmacodynamics profile. Preclinical data showed that opicapone was nontoxic in an in vitro assay (Kiss et al., 2010) suggesting that it was unlikely to have liver toxicity, unlike tolcapone (another COMT inhibitor). Interestingly, while opicapone is rapidly cleared from plasma (Cmax at 1.5-3.5 hours following a single dose and 1-2.5 hours after multiple doses), the half-life of opicapone-induced COMT inhibition in erythrocytes is >100 hours (Rocha et al., 2013). This is due to opicapone’s very slow dissociation rate from COMT. 

The clinical efficacy of opicapone was shown in two Phase 3 clinical trials, BIPARK I (NCT01568073) and BIPARK II (NCT01227655).  

BIPARK I (Ferreira et al., 2016):  This was a randomized, double blind, placebo controlled, and active controlled trial of opicapone as an adjunct to levodopa in patients with Parkinson’s disease with end-of-dose motor fluctuations. A total of 600 patients were randomly assigned 1:1:1:1:1 to receive placebo, entacapone, 5 mg opicapone, 25 mg opicapone, or 50 mg opicapone. The following charts show that patients in the 50 mg opicapone group were significantly more likely to experience less time in the ‘off’ state compared to placebo (panel B; P=0.0015) and that 50 mg opicapone was non-inferior to entacapone (panel C; P=0.0051). Opicapone was well tolerated, with a very low percentage of patients discontinuing due to treatment-emergent adverse events and ≤7% of patients in all groups experiencing serious treatment-emergent adverse events, of which 35% were deemed unrelated to study drug. 

 


BIPARK II (Lees et al., 2016): This was a randomized, double blind, placebo controlled trial to evaluate the safety and efficacy of opicapone as adjunct to levodopa therapy. A total of 427 patients were randomized 1:1:1 to receive placebo, 25 mg opicapone, or 50 mg opicapone for a total duration of 14-15 weeks. This was followed by a 52-week open label extension phase. At the end of the double-blind phase, the mean change in ‘off’ time was -64.5 min for placebo group, -101.7 min for the 25 mg opicapone group, and -118.8 min for the 50 mg opicapone group. The adjusted treatment difference compared with the placebo group was significant for the 50 mg opicapone group (P=0.008), but not for the 25 mg opicapone group (P=0.11). ‘Off’ time reduction was sustained through the open label extension phase as the adjusted mean change from start to finish of the open label phase in ‘off’ time was       -18.3 min. Overall, opicapone was well tolerated with most adverse events being mild or moderate in intensity. The most common adverse events were dyskinesia, constipation, and dry mouth. There were no relevant liver function findings in either phase of the trial.

Numerous Readouts Ahead in 2018


Neurocrine enjoyed a very successful 2017 and will look to keep the momentum going in 2018 with a number of important readouts throughout the year. 

• AbbVie is expected to release Phase 3 data for elagolix in the treatment of uterine fibroids in the first quarter of 2018. Based on strong Phase 2 data we anticipate positive results from the Phase 3 study. 

• A PDUFA decision for elagolix in the treatment of endometriosis is expected in the second quarter of 2018.

• Neurocrine is currently conducting a Phase 2, proof-of-concept study of NBI-74788 in adults with classic, 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH). The study is evaluating how NBI-74788 exposure correlates with specific steroid hormone levels. We anticipate data in the first half of 2018.  

• Late in 2018 we anticipate results from the Phase 2 T-Force GOLD study of INGREZZA® in pediatric patients with Tourette syndrome (TS). This is a multicenter, randomized, double blind, placebo controlled Phase 2b study that expects to enroll approximately 120 pediatric patients ages 6-18. While the T-Force GREEN study did not meet the primary endpoint (change in the Yale Global Tic Severity Scale, YGTSS), we believe the T-Force GREEN study has a higher probability of being positive as the company will be using a higher dose of INGREZZA® based on exposure-response analysis from the T-Force GREEN study.

Financial Update

On February 13, 2018, Neurocrine announced financial results for the fourth quarter and full year 2017. The company reported revenues for INGREZZA® of $64.5 million for the fourth quarter of 2017 and $116.6 million for the full year 2017 (INGREZZA® was launched May 1, 2017). In addition, the company recorded $30 million of milestone revenue from AbbVie in the fourth quarter of 2017 and $45 million in milestone revenue for the full year for total 2017 revenues of $161.6 million. Net income for the fourth quarter of 2017 was $6.9 million, or $0.07 per share, while the net loss for 2017 was $142.5 million, or $1.62 per share. 

For 2017, R&D expenses were $121.8 million, compared to $94.3 million for the same period in 2016. The increase was primarily due to a $30 million payment in the first quarter of 2017 to BIAL for the development and commercialization of opicapone in the U.S. and Canada. SG&A expenses in 2017 totaled $169.9 million, compared to $68.1 million for the same period in 2016. The increase was due primarily to commercialization activities for INGREZZA®. 

As of Dec. 31, 2017, the company had cash, cash equivalents, and investments of approximately $763.3 million. Neurocrine has guided for total operating expenses in 2018 of $365 million to $395 million, with approximately $50 million in stock-based compensation. The company did not give guidance for INGREZZA® sales in 2018 while we are currently forecasting sales of $390 million.

Conclusion


Neurocrine continues to impress with the launch of INGREZZA®. There were some concerns that revenues would lag in the fourth quarter of 2017 due to converting patients over to the 80 mg capsule (which was essentially completed by the end of 2017), however this was more than offset by the strong growth in prescriptions. We believe revenue and prescription growth will remain strong in 2018. Our valuation now stands at $90 per share, and we believe that Neurocrine would make a solid core holding for any biopharmaceutical investor. 

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