European Commission Approves XEPLION(R) for Treatment of Schizophrenia

BEERSE, Belgium, March 9, 2011 /PRNewswire/ -- Janssen-Cilag International NV today announced that XEPLION(R) (paliperidone palmitate), a once monthly, long-acting injectable, antipsychotic, has received approval from the European Commission for the treatment of schizophrenia.

Schizophrenia is relatively common and the prevalence is similar around the world. The lifetime risk for schizophrenia is estimated to be one person in 100, and appears to be the same for men and women up to age 60 years.[1] Schizophrenia is a devastating mental illness for both the patients and their families and friends, as it seriously impairs a person's ability to think clearly, relate to others and to function properly in society. While there is no cure, many people with the illness respond well to antipsychotic medicines, the mainstay of treatment for schizophrenia.

However, further relapses can have a terrible effect on the lives of patients with schizophrenia and their families. Frequent relapses and hospitalisation can increase the person's isolation and make it even more difficult for them to find and keep a job.[2],[3],[4],[5],[6] Prevention of future relapses is a crucial goal of therapy and patients who stay on continual treatment are more likely to achieve optimal outcomes.[7],[8]

Patients with schizophrenia who are non-adherent to medication are up to five times more likely to relapse than those patients who are adherent and continue on medication, significantly increasing the likelihood of hospitalisation,[9] which in turn increases the overall cost of care.

"Relapse can have a devastating effect on patients with schizophrenia and more needs to be done to actively improve adherence to medication if we are to break the cycle of decline," said Professor Fernando Cañas, Head of Department of Psychiatry, Hospital Dr Rodríguez Lafora, Madrid, Spain.* "Long-acting injectable antipsychotics such as XEPLION(R) can help patients to maintain continual treatment, thereby reducing the likelihood of relapse. This is imperative not only to reduce the suffering and cost burden associated with relapse in schizophrenia, but to improve the future outlook and overall quality of life for these patients."

The Clinical Data

The efficacy of XEPLION(R) was established in four double-blind placebo controlled studies in patients with an acute exacerbation of schizophrenia and a longer-term double blind relapse prevention/maintenance study.[10],[11] ,[12],[13],[14] XEPLION(R) was superior to placebo in improving symptoms of schizophrenia as measured by the change in the positive and negative syndrome scale (PANSS) total scores from baseline to endpoint in the acute treatment trials and significantly delayed time to relapse vs. placebo in the longer-term maintenance study.[15]

The most recent acute symptom control study was a multi-centre, randomised, placebo-controlled, double-blind, parallel-group study (n=636). [10] All patients received a dose of 150 mg eq. on Day 1 in the deltoid muscle. From Day 8 and monthly thereafter, patients were assigned to one of three fixed doses of XEPLION(R) (25, 100 and 150 mg eq) administered into either the deltoid or gluteal muscle for a period of 13 weeks. All three doses of XEPLION(R) were superior to placebo in improving the PANSS total score at endpoint (the primary measure of efficacy). The results support efficacy across the entire duration of treatment, with onset of efficacy and significant improvement in PANSS compared to placebo observed from day 8 in some patients. The results of the other studies also yielded significant results in favour of XEPLION(R).[13]

The efficacy of XEPLION(R) in maintaining symptomatic control and delaying relapse in schizophrenia was established in a longer-term, randomised, double-blind, placebo-controlled, flexible-dose study involving 849 patients with schizophrenia.[14] A total of 410 stabilised patients were randomised to either XEPLION(R) or to placebo until they experienced a relapse of schizophrenia symptoms in the variable length double-blind phase of the study. The trial was stopped early for efficacy reasons as a significantly longer time to relapse (p < 0.0001) was seen in patients treated with XEPLION(R) compared to placebo. During the double-blind phase of the study, fewer patients treated with XEPLION(R) experienced a relapse (10% [n=15/156]) compared with those in the placebo group (34% [n=53/156]).[14] The final analyses confirmed the results of the interim analysis.

"XEPLION(R) provides healthcare professionals with the opportunity to rethink their overall approach to how they treat schizophrenia by using long-acting therapies," says Dr Christophe Tessier**, Medical Affairs Director, Psychiatry, Janssen EMEA. "The approval of XEPLION(R) demonstrates Janssen's ongoing commitment to providing novel therapies for schizophrenia. As a once monthly injection, XEPLION(R) can help healthcare professionals address the issue of non-adherence to medication thus ensuring symptom control and allowing patients to focus on shaping their lives."

About XEPLION(R) (paliperidone palmitate)

XEPLION(R) is a once-monthly, long-acting, injectable, atypical antipsychotic. XEPLION(R) will be available in Europe in milligrams (mg) of paliperidone palmitate in dose strengths of 25***, 50, 75, 100 and 150 mg. After the first two initiation injections, XEPLION(R) can be administered in either the deltoid (arm) or gluteal (buttock) muscle.

The approved indication is:

XEPLION(R) is indicated for maintenance treatment of schizophrenia in adult patients stabilised with paliperidone or risperidone. In selected adult patients with schizophrenia and previous responsiveness to oral paliperidone or risperidone, XEPLION(R) may be used without prior stabilisation with oral treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is needed.

Tolerability

In the clinical development programme XEPLION(R) was generally well tolerated with no new safety signals identified in comparison to oral paliperidone ER with the exception of local injection site reactions.[10-14] The most frequently reported adverse effects during the clinical trials were insomnia (difficulty sleeping), headache, weight increase, injection site reactions, agitation, somnolence, akathisia (restlessness), nausea, constipation, dizziness, tremor, vomiting, upper respiratory tract infection (infection of the nose, throat, or chest), diarrhoea, and tachycardia (rapid heart rate).[15]

XEPLION(R) was developed utilising Elan Drug Technologies' proprietary NanoCrystal(R) Technology. Using this technology increases the rate of dissolution and enables the formulation of an aqueous suspension for once-monthly intramuscular administration.

About Schizophrenia

Schizophrenia is a chronic, severe and disabling brain disorder that seriously impairs a person's ability to think clearly, relate to others and to function productively in society. The consequences of the disorder include difficulties in thought processes leading to hallucinations, delusions, disordered thinking and unusual speech or behaviour.

About Janssen

Janssen-Cilag International NV is one of the Janssen Pharmaceutical Companies of Johnson & Johnson, which are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology (e.g. multiple myeloma and prostate cancer), immunology (e.g. psoriasis), neuroscience (e.g. schizophrenia, dementia and pain), infectious disease (e.g. HIV/AIDS, Hepatitis C and tuberculosis), and cardiovascular and metabolic diseases (e.g. diabetes). Driven by our commitment to patients, we develop sustainable, integrated healthcare solutions by working side-by-side with healthcare stakeholders, based on partnerships of trust and transparency. More information can be found at http://www.janssen-emea.com

(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Janssen-Cilag International NV's and/or Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 2, 2011. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither Janssen-Cilag International NV nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

Notes

* Professor Fernando Cañas has at times been a paid consultant of Janssen.

** Dr Christophe Tessier is a full time employee of Janssen, EMEA.

*** 25mg will not be available in all countries.

References

---------------------------------

[1] Lehman A et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1-56

[2] Thornicroft G, Brohan E, Rose D, et al for the INDIGO Study Group. Lancet.2009;373(9661):408-15.

[3] Marwaha S, Johnson S, Bebbington P, et al. Br J Psychiatry. 2007;191:30-7.

[4] Marwaha S, Johnson S. Soc Psychiatry Psychiatr Epidemiol. 2004;39(5):337-49.

[5] Nithsdale V, Davies J, Croucher P. J Occup Rehabil. 2008;18(2 ):175-82.

[6] Rosenheck R, Leslie D, Keefe R, et al; CATIE Study Investigators Group. Am J Psychiatry. 2006;163(3):411-417.

[7] Masand PS, Roca M, Turner MS et al. Partial adherence to antipsychotic medication impacts course of illness in patients with schizophrenia: a review. Prim Care Companion J Clin Psychiatry. 2009;11(4):147-54.

[8] Peuskens J, Olivares JM, Pecenak J et al. Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries. Curr Med Res Opin 2010;26:501-509

[9] Kane JM. Treatment adherence and long-term outcomes. CNS Spectrums. 2007: 12 (10 Suppl 17), 21-26.

[10] Pandina et al. A Randomised, Placebo Controlled Study to Assess the Efficacy and Safety of 3 Doses of paliperidone Palmitate in Adults With Acutely Exacerbated Schizophrenia. J Clin Psychopharmacol. 2010; 30: 235-244.

[11] Nasrallah HA et al. A controlled evidence based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia. Neuropsychopharmacology. 2010; 35(10): 207-282.

[12] Gopal S et al. Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study. Int Clin Psychopharmacology. 2010; 25(5): 24756

[13] Kramer et al. Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study. Int J Neuropsychopharmacology. 2009; 27: p113.

[14] Hough D et al. Paliperidone palmitate maintenance treatment in delaying the time to relapse in patients with schizophrenia: A randomized, double-blind placebo-controlled study. Schizophrenia Research. 2010; 116 (23): 107-117.

[15] Xeplion(R) SmPC 2011