Positive Results of INGREZZA on Tarditive Dyskinesia Highlights Neurocrine Biosciences Sciences and Scientists
The results published online by The American Journal of Psychiatry demonstrate that Phase 3 trial with Neurocrine Biosciences (NBIX) drug Ingrezza conducted on patients with tardive dyskinesia showed significant and meaningful reduction in symptoms.
The positive results came out of the Kinect 3 -- a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study conducted on 234 subjects with tarditive dyskinesia (TD) and underlying schizophrenia, schizoaffective disorder or mood disorder (including bipolar disorder or major depressive disorder).
The participants received six weeks of once-daily INGREZZA (40mg or 80mg capsules) or placebo. Subsequent to the completion of the six-week placebo-controlled dosing, all subjects were placed on once-daily 40mg or once-daily 80mg of INGREZZA through week 48.
Tardive dyskinesias (TDs) are involuntary movements of the tongue, lips, face, trunk, and extremities that occur in patients treated with long-term dopaminergic antagonist medications. People with schizophrenia, and other neuropsychiatric disorders are vulnerable to TDs following exposure to conventional neuroleptics, anticholinergics, toxins, substances of abuse, and other agents. The condition is most common with schizophrenia, and bipolar disorder patients who have been treated with antipsychotic medication for long periods. Occasionally TD occurs also in people with fetal alcohol syndrome and other brain disorders after receiving only 1 dose of the causative agent.
Acute effects of dopamine antagonists also include parkinsonian syndromes manifested by bradykinesia, rigidity, and pill rolling tremor. The acute movement disorders resulting from exposure to dopamine antagonists are commonly termed extrapyramidal syndromes (EPSs).
Ingrezza (valbenazine) was developed in the Neurocrine laboratories by the firm’s scientists is a novel, selective VMAT2 inhibitor that modulates dopamine release during nerve communi-cation, showing little or no affinity for VMAT1, other receptors, transporters and ion channels. Ingrezza is designed to provide low, sustained, plasma and brain concentrations of active drug to allow for once-daily dosing.
The drug’s target VMAT2, is a protein in the human brain, which is responsible for re-packaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) in pre-synaptic neurons.
Modulation of neuronal dopamine levels in diseases such as tardive dyskinesia, Tourette syndrome, Huntington's chorea, schizophrenia, and tardive dystonia, which are characterized in part by a hyperdopaminergic state, may provide symptomatic benefits for patients with these diseases.
There no current FDA approved medications for tardive dyskinesia. The common approach to address the condition has been to discontinue antipsychotic treatment or reduce the dosage, which may often have a negative impact on the psychiatric status of individuals suffering from TD. Christopher F. O'Brien, Chief Medical Officer of Neurocrine said that the results of the Kinect 3 study indicate that Ingrezza significantly reduced tardive dyskinesia symptoms while maintaining stability of psychiatric status during treatment.
KINECT 3 TRIAL RESULTS
The study met its primary endpoint of change-from-baseline at week six in the 80mg once-daily dosing group compared to placebo.
The percentage of participants who achieved a reduction greater than or equal to 50 percent from baseline in dyskinesia score was higher in the Ingrezza 80mg/day group compared to placebo at all study visits.
At week six, 40 percent of participants receiving 80mg/day of INGREZZA had at least a 50% improvement as compared to only 8.7% of placebo.
During the six-week placebo-controlled treatment period Ingrezza was generally well tolerated and the most common adverse reactions were somnolence and drooling. The frequency of adverse events was similar among all treatment groups and treatment emergent adverse effects were consistent with those of prior studies. There were no drug-drug interactions identified in subjects who were utilizing a wide range of psychotropic and other concomitant medications.
Neurocrine has submitted a New Drug Application (NDA) to the FDA for the approval of Ingrezza, which has been granted Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of April 11, 2017.
Neurocrine received Breakthrough Therapy Designation from the FDA in 2014 for Ingrezza for the treatment of TD.
The expected approval of Ingrezza promises adding another drug to its approved drugs, which would mean more revenues and more income for NBIX. Regarding cash, Neurocrine has probably a little less than $300 million, which, according to the company is enough to cover two years, including the launch of Ingrezza (temporarily ignoring the possible revenues from Ingrezza in case it will be approved, which many analysts believe will be the case.)
- Ingrezza’s PDUFA date is April 11, which is very near. An approval here would bring good news that could further boost the stock price. We have no reason for pessimism regarding the approval of this drug. However, delays could happen, as usually do.
- Filing for elagolix: Neurocrine collaborating partner on this drug, Abbvie, intends to file for the approval of this drug in Q3 2017. Neurocrine’s responsibility towards this drug has ended the moment it signed the development agreement with Abvvie and has nothing to do now or following the approval of elagolix except reaping the fruits of the successful outcome of the drug.
- Reaching Phase 3 with Ingrezza for Tourette Syndrome: Neurocrine has an ongoing placebo-controlled Phase 2 Tourette syndrome study evaluating Ingrezza in pediatrics, the T-Force GREEN study. The firm has an ongoing open-label, fixed-dose rollover study of Ingrezza in up to 180 subjects with Tourette syndrome. The results of this study will be announced around June, i.e., a couple of moths from now. In case the drug passes this test, moving into Phase 3 trial of Ingrezza for Tourette syndrome will be another catalyst that could push the stock further up.
- Meeting with the FDA for NDA submission of OnGentys for Approval: Ongentys® (opicapone) -- a once-daily, peripherally-acting, highly-selective catechol-O-methyltransferase inhibitor was approved in June 2016 by the European Commission as an adjunct therapy to preparations of levodopa/DOPA decarboxylase inhibitors for adult patients with Parkinson’s disease and end-of-dose motor fluctuations who cannot be stabilized on those combinations. The approval was granted for the developer BIAL Pharma. In February Neurocrine entered into an exclusive licensing agreement with BIAL, upon which it secured the commercial rights in the United States and Canada.
Upon the agreement, Neurocrine made an upfront payment of $30 million and will fund the development activities necessary for the FDA approval. BIAL is eligible to receive additional milestone payments of approximately $115 million from Neurocrine for the achievement of certain development, regulatory and commercial milestones. In addition, Neurocrine will pay BIAL a percentage of net sales in exchange for the manufacture and supply of opicapone drug product.
We believe the deal was a successful choice at the right time.
Stock Exchange: NASDAQ
Stock Symbol: NBIX
Stock Price: $42.17
52-week range: $33.56 -- $55.15
Market Cap: $3.67 Billion
Central Nervous System:
Ingrezza: NDA filed for Approval for tarditive dyskinesia:
Ingrezza: In Phase 2 Trial for Tourette Syndrome
NBI-640756: In Phase 1 for Essential Tremor
Opicapone: In Phase 3 for Parkinson’s Disease
Elagolix: In Phase 3 for endometriosis
Elagolix: In Phase 3 for uterine Fibroids
Final Word: We believe 2017 will be a good year for NBIX, whose stock has somewhat outperformed and a successful outcome of the catalysts cited above, we expect the stock to further outperform.
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