The European Commission Grants Camurus Marketing Authorisation for Weekly and Monthly Buvidal® for Opioid Dependence

LUND, Sweden, November 22, 2018 /PRNewswire/ --

• Buvidal^®is the first long-acting medicine approved in the EU for the treatment of opioid dependence in adults and adolescents

Camurus announced today that the European Commission has granted marketing authorisation for Buvidal^® (CAM2038), the first and only long-acting injectable treatment available in both weekly and monthly formulations in the EU, that is indicated for the treatment of opioid dependence within a framework of medical, social and psychological treatment in adults and adolescents aged 16 years or over.

"The marketing authorisation of Buvidal^® is a significant step forward in addressing the substantial unmet need in opioid dependence by delivering a new, long-acting and flexible treatment option. We are committed to making Buvidal^® available for patients as soon as possible, with the initial wave of country launches scheduled for the first quarter of 2019," said Fredrik Tiberg, President & CEO of Camurus. "This approval represents a major milestone for the company. Our first long-acting medicine validates our FluidCrystal^® technology which is the foundation of our extensive development pipeline of new drug candidates."

Opioid dependence is a chronic, relapsing brain disease that involves a physical and psychological need for opioids that causes major medical, social and economic problems to both the individual and society.^[1] Similar to other chronic diseases, like type 2 diabetes, hypertension and asthma, opioid dependence often involves cycles of relapse and remission and has comparable relapse rates.^[2] In the UK, over 330,000 high-risk users are injecting or using opioids regularly, with less than half receiving medical treatment.^[3] The latest figures show the number of people dying from opioid-related drug misuse has reached a record high in England and Wales, with almost 9 in 10 drug-related deaths involving an opioid.^[3]

Buvidal^® offers a treatment that can be individualised to specific patient needs due to flexible, weekly and monthly doses that allows for dose conversion from sublingual buprenorphine, can improve treatment outcomes and reduce the burden, risks and stigma of daily dosing. Formulated with Camurus' proprietary FluidCrystal^® injection depot technology, Buvidal^® is an innovative lipid-based solution which, once injected, transforms into a gel-like depot. The depot slowly biodegrades over time, releasing the buprenorphine which blocks the drug-liking effect of opioids in the brain and reduces withdrawal, craving and patient's use of illicit opioids.^{[4],[5],[6],[7]}

"Patients with opioid dependence in Europe are in great need of new and more effective medications that can improve treatment outcomes and quality of life," says Professor Sir John Strang, Director of the National Addiction Centre, King's College, London. "Buvidal weekly and monthly subcutaneous injection depots could become a game-changer in opioid dependence treatment by improving adherence and reducing the burden, stigma and risks of daily treatment."

The marketing authorisation is based on a comprehensive clinical programme of seven Phase 1-3 clinical trials demonstrating that Buvidal^® delivers clinically proven rapid, predictable and sustained release of buprenorphine over a week or month.^[5] In the pivotal Phase 3 study, Buvidal^® was shown to be at least as effective as standard treatment with daily buprenorphine / naloxone for the primary endpoint of the mean percent urine tests negative for illicit opioids (p<0.001). Superior treatment effect was demonstrated for the key secondary endpoint of cumulative distribution function for the percent urine tests negative for illicit opioid use (p=0.008).^[5] The safety profile of Buvidal was comparable to daily SL BPX, except for mild to moderate injection site reactions. The most common side effects of Buvidal^® are headache, nausea, hyperhidrosis, insomnia and mild-to-moderate injection-site reactions.

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About opioid dependence/opioid use disorder 

Opioid dependence is a serious, chronic, relapsing disease that can affect all aspects of a person's daily life. It is an escalating global health problem, contributing to significant adverse mental, physical, and social consequences, including unemployment, criminal activity, incarceration, transmission of infectious diseases, unintentional overdose and death.^[8] According to the World Drug Report, approximately 34 million individuals globally use opioids for non-medical purposes and an estimated 127,000 people die each year from opioid overdoses.⁸ Opioids top the list of drugs that cause the greatest burden of disease and drug-related deaths worldwide. In Europe, an estimated 1.3 million people engage in high-risk opioid use, with only about 630,000 receiving medical treatment.³ Each year, about 9,000 Europeans die from drug-related overdoses. The numbers are even higher in the US with about 2.6 million people diagnosed with opioid use disorder and close to 50,000 dying from opioid overdose in 2017.^[9] This is now the most common cause of death in people in the US under 50 years of age.^[10]

About Buvidal^®  

Buvidal (buprenorphine prolonged release solution for subcutaneous injection in prefilled syringe) has been developed for the treatment of opioid dependence within a framework of medical, social and psychological treatment. Buvidal is designed for flexible dosing and is available in four weekly strengths (8, 16, 24 and 32 mg) and three monthly strengths (64, 96, and 128 mg), enabling treatment to be tailored to the patient's individual needs. Buvidal is administered by healthcare professionals to enhance treatment adherence, while potentially minimizing the risks of diversion, misuse, overdose and accidental exposure to children and teenagers.

The EC marketing authorization of Buvidal^® is based on a comprehensive clinical program with seven clinical studies, including a randomized, double-blind, double-dummy, active controlled Phase 3 study in 428 patients with opioid dependence. In this pivotal study, Buvidal was shown to be at least as effective as effective as standard treatment with daily buprenorphine/naloxone (SL BPX) for the primary endpoint of the mean percent urines negative for illicit opioids (p<0.001). The least square mean was 35.1% for treatment with Buvidal versus 28.4% for standard treatment with SL BPX. Superiority was met for the key secondary endpoint of cumulative distribution function (CDF) for the percent urine tests negative for illicit opioid use. The median CDF for Buvidal was 26.7% and 6.7% for SL BPX (p=0.008).^[5] The safety profile of Buvidal was comparable to daily SL BPX, except for mild to moderate injection site reactions. The most common side effects of Buvidal^® are headache, nausea, hyperhidrosis, insomnia and mild-to-moderate injection-site reactions.

Formulated with Camurus' FluidCrystal^® injection depot technology, Buvidal is presented ready for use in pre-filled syringes for weekly or monthly administration as small dose volume subcutaneous injection through a thin, 23-gauge needle. Buvidal has been developed for room temperature storage, avoiding the need for cold chain distribution and refrigerator storage. Therefore, no mixing steps or room temperature conditioning are required prior to administration.

About Camurus  

Camurus is a Swedish research-based pharmaceutical company committed to developing and commercialising innovative and differentiated medicines for the treatment of severe and chronic conditions. New drug products with best-in-class potential are conceived based on the company's proprietary FluidCrystal® drug delivery technologies and its extensive R&D expertise. Camurus' clinical pipeline includes products for the treatment of cancer, endocrine diseases, pain and addiction, which are developed in-house and in collaboration with international pharmaceutical companies. The company's shares are listed on Nasdaq Stockholm under the ticker CAMX. For more information, visit www.camurus.com .

References

1. Maremmani I, Pacini M, Pani PP. Basics on addiction: a training package for medical practitioners or psychiatrists who treat opioid dependence. Heroin Addiction and Related Clinical Problems. 2011 Jun 1;13(2):5-40.

2. McLellan AT, Lewis DC, O'brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000 Oct 4;284(13):1689-95.

3. European Monitoring Centre for Drugs and Drug Addiction. United Kingdom Drug Report 2018. Available at: http://www.emcdda.europa.eu/system/files/publications/8894/united-kingdom-cdr-2018-with-numbers.pdf.  Last accessed November 2018.

4. Albayaty M, Linden M, Olsson H, Johnsson M, et al. Pharmacokinetic evaluation of once-weekly and once-monthly buprenorphine subcutaneous injection depots (CAM2038) versus intravenous and sublingual buprenorphine in healthy volunteers under naltrexone blockade: an open-label Phase 1 study. Adv Ther 2017; 34(2):560-575.

5. BUVIDAL 8 mg, 16 mg, 24 mg, 32 mg, 64 mg, 96 mg, 128 mg prolonged-release solution for injection SmPC.

6. Walsh SL, Comer SD, Lofwall MR, et al. Effect of buprenorphine weekly depot (CAM2038) and hydromorphone blockade in individuals with opioid use disorder: a randomized clinical trial. JAMA psychiatry 2017; 74(9):894-902.

7. Haasen C, Linden M, Tiberg F. Pharmacokinetics and pharmacodynamics of a buprenorphine subcutaneous depot formulation (CAM2038) for once-weekly dosing in patients with opioid use disorder. Journal of substance abuse treatment 2017; 78:22-29.

8. World Drug Report 2018 (United Nations publication, Sales No. E.18.XI.9). Available at: http://www.unodc.org/wdr2018/en/topics.html  Accessed November 2018. Last accessed November 2018.

9. National Institute on Drug Abuse 2018. Available at: http://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates.  Last accessed November 2018.

10. Centers for Disease Control and Prevention 2018. Available at: http://www.cdc.gov/drugoverdose/data/. Last accessed November 2018.

INT-BUV-1800003
Date of preparation: November 2018