dm+d

Unassigned

New Medicines

IngrezzaTardive dyskinesia

Information

Ingrezza
New molecular entity
Neurocrine Biosciences
Neurocrine Biosciences

Development and Regulatory status

None
None
Launched

Feb 19: In its 2018 annual report, Neurocrine provides no update on any plans for further development of Ingrezza in additional markets. Launch in the UK in the near future seems unlikely [21].


May 18: Neurocrine intends to establish agreements with other partners in order to commercialise valbenazine [20].


Dec 17: Neurocrine Biosciences has an agreement with Mitsubishi Tanabe Pharma for development and commercialisation of valbenazine in Asia. No information available regarding plans for development in Europe [18,19].


May 17: Launched in the US [16].


Apr 17: Approved in the US, the first medicine licensed for TD. It will be launched in May [14].


Nov 16: According to Neurocrine Biosciences, the New Drug Application (NDA) will be reviewed by the FDA Psychopharmacologic Drugs Advisory Committee on 16th February 2017: the application has a target action date of 11th April 2017 [11].


Oct 16: Accepted for priority review in US on basis of data from Kinect 2 and Kinect 3 [10].


Aug 16: Filed in the US. The company expects its submission to be accepted by October, giving it an expected PDUFA date in April, should it get an accelerated review [8].


Oct 15: Neurocrine Europe Ltd. was formed during Dec 14 [7].


Oct 15: Neurocrine has full commercial rights to NBI-98854 in North America, Europe and other countries outside of Asia [7].


Oct 15: Submission of New Drug Application Planned for 2016 [6].


Oct 14: The FDA grants Breakthrough Therapy Designation for NBI-98854 for treatment of tardive dyskinesia [4].

Category

Highly-selective VMAT2 inhibitor
The risk of new cases is around 5% per year of cumulative drug exposure. In elderly individuals receiving antipsychotic medications for the first time, the incidence was generally fivefold higher. It occurs in 20% of those on chronic therapy and persists in 40% of cases after discontinuation of therapy. [2]
Tardive dyskinesia
Oral

Trial or other data

Oct 18: While there may not be another TD med out there in the US when Ingrezza hits the scene, Neurocrine does have a competitor waiting in the wings (Austedo, approved for Huntington disease). Austedo is currently waiting for its own TD decision from the FDA, due by late August. Ingrezza will be competitively priced with Austedo, which bears a $60,000 price tag. Neurocrine is hoping a couple key differences between the meds will give Ingrezza a lift. Austedo requires a titration process; Ingrezza is a fixed-dose product, with patients receiving either 40 mg or 80 mg. Ingrezza is also dosed once-daily, compared with twice-daily Austedo [14].


Nov 17: Results of 1-Year KINECT 3 Extension Study (n=198) published. Long-term safety and tolerability of valbenazine were generally favourable (69.2% had ≥ 1 ADR, 14.6% serious ADR, and 15.7% discontinued due to ADR) and maintenance of treatment effect was apparent with both 40 and 80mg doses [17].


Apr 17: Neurocrine has priced Ingrezza at $5,275 for a 30-count bottle of 40 mg capsules (a yearly sum of $63,30). Neurocrine is also this year anticipating an FDA go-ahead for its 80 mg version, which will be priced substantially similar to its 40 mg counterpart [15].


Mar 17: Neurocrine publishes additional dat from a PIII trial. The trial showed 80 mg per day doses of Ingrezza produced statistically-significant changes over placebo in scores on the Abnormal Involuntary Movement Scale (AIMS), resulting in it hitting its primary endpoint. Neurocrine also reported a significant difference in the proportion of patients in the drug and placebo arms whose AIMS score improved by 50% or more over the course of the study. The only adverse events to affect more than 5% of patients in the treatment arms were drowsiness and dry mouth. And the dropout rates due to adverse events were comparable across all the arms [13].


Jan 17: A PII trial misses its primary endpoint. Investigators enrolled 124 patients with Tourette syndrome in the trial and randomised them to receive one of two doses of Ingrezza or a placebo. After eight weeks of treatment, the change from baseline against the Yale Global Tic Severity Scale (YGTSS) and other scales was evaluated. Ingrezza failed to outperform placebo against YGTSSt. There was a significant improvement in one secondary endpoint - a symptom scale, the Clinical Global Impression of Change. Neurocrine is not disclosing specific details of this study in order to avoid the potential introduction of assessment bias in the ongoing phase 2 T-Force GREEN study of pediatric Tourette patients [12].


Sep 16: Teva announces data from the 12-week AIM-TD study of deutetrabenazine, a closely-following competitor for valbenazine: these showed likely similar efficacy [9].


Oct 15:Top-line efficacy data from PIII Kinect 3 Study show that the AIMS ratings at Week 6 for pts on 80mg once-daily NBI-98854 were reduced by 3.1 points more than placebo (p<0.0001). NBI-98854 was generally well tolerated and the frequency of adverse events was similar among all treatment groups and treatment emergent adverse effects were consistent with those of prior studies [6].


Aug 15: Subject randomisation of the PIII Kinect 3 study has been completed [5].


Oct 14: Initiation of PIII Kinect 3 trial announced. This randomised, parallel-group, double-blind, placebo-controlled trial wil enroll 240 pts with moderate to severe tardive dyskinesia and an underlying diagnosis of mood disorder, schizophrenia or schizoaffective disorder. The initial six weeks of treatment consists of an efficacy and safety assessment of 80mg and 40mg once-daily NBI-98854 against placebo and is followed by 46 weeks of long-term safety assessment in which all pts are randomised in a blinded fashion to either 80mg or 40mg once-daily NBI-98854. The primary endpoint will be the mean change from baseline in the Abnormal Involuntary Movement Scale (AIMS) as assessed by blinded study personnel. Top-line efficacy data from the initial six weeks of placebo-controlled dosing is expected in the second half of 2015. The Company also intends to conduct a separate one-year, open-label safety study of NBI-98854 to support the anticipated filing of a New Drug Application (NDA). [3]


Jan 14: Results in Jan 2014 showed PII Kinect 2 trial met its primary endpoint; demonstrated significant improvements in the Abnormal Involuntary Movement Scale (AIMS) score at 6 weeks in pts treated with valbenazine at dosages of ≤75 mg/day, compared with those who received placebo. These results were in contrast to results from the earlier phase II Kinect trial, in which valbenazine lacked efficacy at those dose levels. Based on these outcomes, Neurocrine Biosciences intends submitting an End-of-Phase-II meeting request to the US FDA [1]