Outcome of Phase 3 Trial of RBP – 700005.05.2015 | PDF Version
FOR IMMEDIATE RELEASE
Indivior PLC Announces Posi ve Top‐line Results From Pivotal Phase 3 Trial of RBP‐ 7000 in Schizophrenia
Slough, UK, 5 May 2015‐ Indivior PLC (LON: INDV) today announced top‐line results from its phase 3 clinical trial of RBP‐7000, an inves ga onal drug in development for the treatment of schizophrenia. In this pivotal study, both doses of RBP‐7000 tested, 90 mg and 120 mg administered once‐monthly, met the primary endpoint with sta s cally and clinically signiﬁcant reduc ons in the symptoms of acute schizophrenia over an 8‐week treatment period. Symptom reduc on was measured using the change from baseline to end of treatment in the total Posi ve and Nega ve Syndrome Scale (PANSS) scores. RBP‐7000 also met the key secondary endpoint with sta s cally signiﬁcant improvements in the Clinical Global Impression‐Severity of Illness (CGI‐S) scale compared with placebo over the 8‐week treatment period using change from baseline to end of treatment.
“With these posi ve phase 3 data in hand, we are moving forward expedi ously to complete the open‐label long‐term assessment of the safety and tolerability of RBP‐7000,” said Chris an Heidbreder, Ph.D., Chief Scien ﬁc Oﬃcer of Indivior. “We understand there is a great unmet need among pa ents living with this chronic disease, and we hope to bring a new, long‐ac ng treatment op on to those individuals and the physicians who treat them.”
Based on the success of the open‐label phase of the trial, Indivior expects to submit a New Drug Applica on (NDA) to the U.S. Food and Drug Administra on for poten al approval in 2017.
During the 8‐week, double‐blind treatment period, pa ents treated once‐monthly with either 90 mg or 120 mg of RBP‐7000 demonstrated sta s cally and clinically signiﬁcant mean reduc ons from baseline in PANSS total scores (‐9.2 points for placebo; ‐15.4 points for RBP‐7000, 90 mg, p=0.0004 vs. placebo; and ‐16.4 points for RBP‐7000, 120 mg, p<0.0001 vs. placebo). In addi on to mee ng the pre‐speciﬁed primary eﬃcacy endpoint of PANSS total score reduc on, the study also met the pre‐ speciﬁed key secondary endpoint of improvement on the CGI‐S scale for each RBP‐7000 group vs. placebo at Week 8 (p=0.0002 vs. placebo for RBP‐7000, 90 mg; and p<0.0001 vs. placebo for RBP‐ 7000, 120 mg). RBP‐7000 was generally well tolerated in the study, and the observed safety proﬁle of RBP‐7000 was similar to that reported with oral risperidone.
Schizophrenia is a chronic, severe and disabling brain disorder1 that aﬀects an es mated 26 million people worldwide.2 Treatment is aimed at reducing or elimina ng the symptoms of the disease and o en includes an psycho c medica ons and various psychosocial treatments.1
About the Study Design
The phase 3, randomized, mul center, double‐blind, placebo‐controlled study was designed to assess the eﬃcacy, safety and tolerability of RBP‐7000 (90 mg and 120 mg) in pa ents experiencing acute exacerba on of schizophrenia. The trial included adult male and female pa ents between the ages of 18 to 55 years who met the Diagnos c and Sta s cal Manual of Mental Disorders, Fourth Edi on, Text Revision (DSM‐IV‐TR®) criteria for schizophrenia and had a PANSS total score between 80 and 120 at the ini al screening visit, and a score of 4 or greater on at least two of the following four items of the PANSS posi ve subscale: hallucinatory behavior, delusions, conceptual disorganiza on or suspiciousness.
A total of 354 pa ents were randomized to receive once‐monthly subcutaneous injec ons of RBP‐ 7000, 90 mg; RBP‐7000, 120 mg; or a matching placebo injec on for 8 weeks. Following randomiza on, pa ents received their ﬁrst injec on of RBP‐7000.
The primary eﬃcacy endpoint of the study was the mean change from baseline at Week 8 in PANSS
total score. Sta s cal analyses of the eﬀect of study treatment vs. placebo on the primary eﬃcacy endpoint were conducted using a mixed eﬀects model for repeated measures taking into account all available observa ons of the primary eﬃcacy endpoint at various visits, and including terms for treatment (RBP‐7000 [90 mg], RBP‐7000 [120 mg], placebo), baseline total PANSS score, visit (5, 6, 8,
9) and treatment‐by‐visit interac on as ﬁxed eﬀects. The unstructured covariance type was used to model the variance‐covariance matrix. Dunne ‘s procedure was used to adjust for the comparison between two levels of study treatment (RBP‐7000 [90 mg and 120 mg]) with a single placebo.
All par cipants who completed the double‐blind por on of the study and met some addi onal inclusionary/exclusionary criteria were eligible to con nue in an open‐label phase and receive RBP‐ 7000 for a total of 13 injec ons (2 in the double‐blind phase and 11 in the open‐label phase). The objec ve of the extension phase of the study is to assess the safety and long‐term tolerability of once‐monthly RBP‐7000.
RBP‐7000 is a novel sustained‐release product using the Atrigel® delivery system for the subcutaneous administra on of risperidone once every month.3 RBP‐7000 consists of a two‐syringe system, whose contents are mixed immediately prior to administra on. One syringe contains the Atrigel® delivery system, and the other contains the powder‐ﬁlled drug substance risperidone. These phase 3 clinical trial results further emphasize the compa bility of our Atrigel® drug delivery pla orm with a range of pharmaceu cal compounds for their safe, sustained release over targeted me period through an easy biodegradable and biocompa ble process.
Schizophrenia is a chronic disorder characterized by a life‐long pa ern of acute psycho c episodes superimposed upon chronically poor psychosocial adjustment. The symptoms can be grouped into four domains: posi ve (e.g., delusions, hallucina ons, disorganized speech and behavior); nega ve (e.g., social withdrawal, avoli on, blunted aﬀect); cogni ve (e.g., impaired sustained a en on, execu ve func on and working memory) and aﬀec ve (e.g., anxiety and depression, hos lity and aggression, increased risk of suicide) symptoms. These occur in diﬀerent combina ons and to a diﬀerent degree in each pa ent. Given the extensive heterogeneity of symptoms among individual pa ents, schizophrenia can be considered a clinical syndrome rather than a single disease en ty. Schizophrenia leads to high direct and indirect costs and accounts for 1.5‐3 percent of na onal healthcare expenditures across countries.3
Indivior is a global specialty pharmaceu cal company with a 20‐year legacy of leadership in pa ent advocacy, health policy and evidence‐based best prac ce models that have revolu onized modern addic on treatment. The name is the fusion of the words individual and endeavor, and the tagline “Focus on you” makes the company’s commitment clear. Indivior is dedicated to transforming addic on from a global human crisis to a recognized and treated chronic disease. Building on its robust, global opioid dependence por olio featuring SUBOXONE® (buprenorphine and naloxone) Sublingual Film (CIII), SUBOXONE® (buprenorphine and naloxone) Sublingual Tablet, and SUBUTEX® (buprenorphine) Sublingual Tablet, Indivior has a strong pipeline of product candidates designed to both expand on its heritage in this category and address other chronic diseases of addic on ‐ including opiate overdose, alcohol use disorders and cocaine intoxica on. It also is pursuing novel product candidates in related mental health disorders such as schizophrenia. Headquartered in the United States in Richmond, Va., Indivior employs more than 700 individuals globally and its por olio is available in over 40 countries worldwide. Visit www.Indivior.com to learn more.
This press release contains forward‐looking statements. We may, in some cases, use terms such as “predicts,” “believes,” “poten al,” “proposed,” “con nue,” “es mates,” “an cipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to iden fy these forward‐looking statements. Forward‐looking statements include, among other things, statements regarding our ﬁnancial guidance for 2015 and our medium‐ and long‐term growth outlook, our opera onal goals, our product development pipeline and statements regarding ongoing li ga on.
Various factors may cause diﬀerences between Indivior’s expecta ons and actual results, including: factors aﬀec ng sales of Suboxone Tablet, Suboxone Film, Subutex Tablet and any future products; the outcome of research and development ac vi es; decisions by regulatory authori es regarding the Indivior Group’s drug applica ons; the speed with which regulatory authoriza ons, pricing approvals and product launches may be achieved; the outcome of post‐approval clinical trials; compe ve developments; diﬃcul es or delays in manufacturing; the impact of exis ng and future legisla on and regulatory provisions on product exclusivity; trends toward managed care and healthcare cost containment; legisla on or regulatory ac on aﬀec ng pharmaceu cal product pricing, reimbursement or access; claims and concerns that may arise regarding the safety or eﬃcacy of the Indivior Group’s products and product candidates; risks related to legal proceedings; the Indivior Group’s ability to protect its patents and other intellectual property; the outcome of the Suboxone Film patent li ga on rela ng to the three ongoing ANDA lawsuits; changes in governmental laws and regula ons; issues related to the outsourcing of certain opera onal and staﬀ func ons to third par es; uncertain es related to general economic, poli cal, business, industry, regulatory and market condi ons; and the impact of acquisi ons, dives tures, restructurings, internal reorganiza ons, product recalls and withdrawals and other unusual items.
Any forward‐looking statements that we make in this press release speak only as of the date of this press release. We assume no obliga on to update our forward‐looking statements whether as a result of new informa on, future events or otherwise, a er the date of this press release.
Amir Khan Beth Keshishian
Biosector 2 Biosector 2
+1 212‐845‐5656 +1 212‐229‐8417
akhan@inven vhealth.com bkeshishian@inven vhealth.com
Indivior, Director, Investor Rela ons
+44 1753 217800