Opko Health Inc (OPK)

[tomsylver]

OPKO Health/Tesaro Rolapitant NDA On Track September 2014

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NDA filing of Rolapitant (partnered with TSRO) for the prevention of chemotherapy induced nausea and vomiting, or CINV, due mid September 2014 ( http://www.biopharmcatalyst.com/fda-calendar/ )

Catalyst Date (due by) 9/15/2014

CINV

Rolapitant

Rolapitant is potentially a best-in-class supportive care product for Chemotherapy-induced nausea and vomiting (CINV). Characteristics include:

* Single dose
* Rapid onset
* Long-acting (5 day activity as opposed to 1 or 2 days for other treatments)

Acquisition of Rolapitant

* In October 2009, OPKO acquired Rolapitant ( http://investor.opko.com/releasedetail.cfm?ReleaseID=415380 ) , a potent and selective competitive antagonist of the NK-1 receptor, in addition to other neurokinin-1 (NK-1) assets from Schering Plough Corporation.
* In December 2010, OPKO exclusively out-licensed the development, manufacture, and commercialization of Rolapitant to biopharmaceutical company TESARO, Inc.

Clinical Development

Rolapitant has completed Phase 3 clinical development for CINV. Two phase 3 trials of rolapitant that together enrolled a total of 1,070 patients receiving highly emetogenic chemotherapy (HEC) and met the primary endpoint of a higher rate of complete response in the delayed phase. The results indicated that protection from CINV was maintained over the full five day at-risk period in both trials. One additional phase 3 trial of rolapitant that enrolled 1,369 patients receiving moderately emetogenic chemotherapy (MEC) successfully achieved the primary endpoint of higher rate of complete response in the delayed phase. a New Drug Application (NDA) is on track for mid-2014.

License Agreement with TESARO

* Under terms of the license with TESARO, OPKO is eligible to receive up-front and milestone payments of up to $121 million.
* OPKO is also entitled to double-digit tiered royalties on sales of the licensed product, a share of future profits from product commercialization in Japan, and an option to market the product in Latin America.
* OPKO has also acquired an equity position in TESARO.

Market Opportunity

* U.S. market opportunity of approximately $1.25 billion
* 6.6 million annual CINV patient treatments in 2011
* NCCN and ASCO guideline recommendations could lead to 70% penetration by the NK-1 class
* Merck-EMEND® (Aprepitant) is currently the only NK-1 receptor antagonist on the market Strong IP portfolio with U.S. exclusivity expected through 2028

Medscape Education Oncology

Audio SlideShow: Updates on the Management of CINV From the 2014 June Congresses ( http://www.medscape.org/viewarticle/830386 )

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Rolapitant Studies Presented At The 2014 MASCC/ISOO Meeting

Released: 08/29/2014

Transcript Excerpt ( http://www.medscape.org/viewarticle/830386_transcript )

Dr Rapoport: Thank you, Harry. The rolapitant studies were presented at the 2014 MASCC/ISOO meeting in the form of oral presentations and as posters at the 2014 annual ASCO® meeting. I am going to start with the MEC study, in which 1369 patients were randomly assigned in a 1:1 ratio to one of the two arms.[19] Either 200 mg of oral rolapitant or placebo was administered 2 hours prior to MEC on day 1. In addition, patients received a standard treatment with 2 mg of oral granisetron and 20 mg of oral dexamethasone 30 minutes prior to administration of MEC. On days 2 and 3, patients received 2 mg of oral granisetron. The rates of emesis and use of rescue medication, as well as other end points such rates of nausea as safety, were recorded for 5 days during cycle 1. However, patients could receive up to 5 additional cycles of chemotherapy and antiemetic agents during the trial.

The primary end point of this study was the rate of complete response (CR) in the delayed phase, which is between 24 and 120 hours following administration of chemotherapy. In the intent-to-treat population, there was a 71% vs 61% control rate with a P-value of .001.The difference between the two arms was also statistically significant (68% vs 57%) in the overall phase, also with a P-value of .001.There was no significant difference between the two arms with respect to CR rate in the acute phase, which was 83% vs 81%.

Also, there were no significant differences in the rate of adverse events between the two arms. The most common adverse events included constipation, fatigue, alopecia, and neutropenia, all of which are frequently seen in most of these antiemetic trials.

Then there were 2 studies looking at HEC chemotherapy: HEC1 and HEC2.[20] There were 532 patients in the HEC1 trial and 555 patients in the HEC2 trial and patients were randomly assigned in a 1:1 ratio in both studies. As in the MEC study, rolapitant at a dose of 200 mg or oral placebo was given 1 to 2 hours prior to the HEC chemotherapy, and patients also received granisetron intravenously at a dose of 10 micrograms per kilogram and 20 mg of oral dexamethasone on day 1. On days 2 through 4, patients received 8 mg of oral dexamethasone twice daily. Again, events of emesis and nausea and the use of rescue medication were recorded for 5 days. Patients were treated for up to an additional 5 cycles.

The primary end point of improvement in delayed CR rate in both the HEC 1 and HEC 2 studies was met:72% for rolapitant vs 58% for placebo with a P-value of .001 in the HEC1 study and 70% vs 61% with a P-value of .04 in the HEC2 study. With the secondary end points, in the HEC 1 study there were significant differences in acute CR rates (83% vs 73%) and overall CR rates (70% vs 56% with a P-value of .001). In the HEC2 study, the difference in acute CR rates was not significant -- 83% vs 79% -- but there was a trend toward improvement in the overall CR rate (67% vs 60%) with a P-value of .08. It is important, again, to mention that results of both of these studies were significant for their primary end points.

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