Long-acting buprenorphine injections like Buvidal can help address some of the limitations of daily-dosed opioid substitution therapies for opioid dependence. Evidence shows that Buvidal provides sustained suppression of withdrawal symptoms and drug cravings from the first dose. It also has favorable retention rates and safety profiles in both short-term and long-term studies compared to sublingual buprenorphine. Buvidal has the potential to improve outcomes for opioid dependence by offering more individualized treatment through less frequent dosing than daily options.

1. Focus on long-acting
opioid substitution
therapy
EHAB ELBAZ, M.D, MBA
CONSULTANT PSYCHIATRIST
LECTURER OF PSYCHIATRY, MILITARY MEDICAL ACADEMY
DIRECTOR OF PSYCHIATRY HOSPITAL , MAADI ARMED FORCES COMPOUND

2. WHY DO WE TREAT THE ADDICTS ?
1. Disley E, Mulcahy A, Pardal M, Rubin J, Ruggeri K. Development of a framework to estimate the cost of opioid dependence. Cambridge, UK: RAND Corporation;2013. 2. European
Monitoring Centre for Drugs and Drug Addiction. European Drug Report: Trends and Developments. 2017. 3. World Health Organization. Guidelines for the Psychosocially Assisted
Pharmacological Treatment of Opioid Dependence. 2009.
Individuals, families and society are harmed by the effects of opioid
dependence1
OPIOID DEPENDENCE IS ASSOCIATED WITH A SIGNIFICANT AMOUNT OF
DRUG-RELATED HARM1–3
HEALTH ISSUES UNEMPLOYMENT CRIME HOMELESSNESS PREMATURE MORTALITY

3. Pharmacological options in the treatment of opioid use disorders

4. Overview of main pharmacological treatments for opioid
dependence
CATEGORY METHADONE BUPRENORPHINE
Brand Names MethadoseTM, Dolophine®, etc Subutex®*, Suboxone®**, Bunavail®, Zubsolv®,
Probuphine®, SublocadeTM,Buvidal®
Pharmacology Long-acting synthetic mu-opioid receptor full
agonist
Synthetic opioid acting as partial agonist at opioid
receptors
Therapeutic effects Can prevent withdrawal symptoms and
reduce craving for opioids in patients with
opioid dependence
• Reduces or eliminates withdrawal symptoms
associated with opioid dependence
• Does not produce the euphoria or sedation
caused by heroin or other opioids at therapeutic
doses
Routes of
administration
Oral Sublingual tablet or film, buccal film, subdermal
implant, or subcutaneous injection
*Subutex is only available as a generic. **Suboxone tablets are only available as a generic. Adapted from SAMHSA TIP 63, NIDA Principles of Drug Addiction
Treatment 2018 and ASAM National Practice Guidelines 2015
Not all products are distributed in all countries.

5. WHAT ARE THE BENEFITS OF (OAT) ?
1. World Health Organization. Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. 2009. 2. European Monitoring
Centre for Drugs and Drug Addiction. United Kingdom. Country Drug Report. 2017.
REDUCING ILLICIT OPIOID USE LOWERS THE RISK OF:1
COMPARED TO NO
THERAPY, PATIENTS ON
OAT SHOW REDUCED
MORTALITY, BLOOD
BORNE VIRUS INFECTIONS,
RISKY BEHAVIOUR AND
LEVELS OF CRIME2
POOR HEALTH
BLOOD BORNE
VIRUSES
OVERDOSE
HOMELESSNESS
AND SOCIAL
EXCLUSION

6. OAT with BPN and MET are the standard of care for treating opioid
dependence
HOWEVER, MANY PATIENTS DO NOT RECEIVE TREATMENT
OF HIGH-RISK OPIOID USERS ARE
NOT IN TREATMENT1
~50%
1. European Monitoring Centre for Drugs and Drug Addiction. European Drug Report: Trends and Developments. 2017,
PHARMACOLOGICAL
TREATMENT FOR OPIOID
DEPENDENCE SHOULD BE A
HEALTHCARE
PRIORITY”
World Health Organization. Guidelines for the
Psychosocially Assisted Pharmacological
Treatment of Opioid Dependence. 20091
“

7. Overview of selected buprenorphine treatments for opioid
dependence
PRODUCT NAME
ACTIVE
INGREDIENT(S)
ROUTE OF
ADMINISTRATION
FREQUENCY OF
ADMINISTRATION
* Not available in all markets ** Currently only available only in US
Product Name Pharmacological Ingredient(s) Route of Administration Frequency of
Administration
Buvidal® Buprenorphine Prolonged release solution for
subcutaneous injection
Weekly or Monthly
Suboxone® Buprenorphine/naloxone Sublingual film* and tablets Daily
Subutex® Buprenorphine Sublingual tablets Daily
Zubsolv® Buprenorphine/naloxone Sublingual tablets Daily
Generic buprenorphine
or buprenorphine/
naloxone
Buprenorphine and buprenorphine/naloxone Sublingual tablets Daily
Bunavail®** Buprenorphine/naloxone Buccal films Daily
Espranor® Buprenorphine Oral tablets (dispersal on tongue) Daily
Probuphine®** Buprenorphine Implants 6 months
SublocadeTM** Buprenorphine Prolonged-release subcutaneouys
injection
Monthly

8. Treatment Limitations for Daily Dosing
1. Maas J, Barton G, Maskrey V, Pinto H, Holland R. Economic evaluation: a comparison of methadone versus buprenorphine for opiate substitution treatment. Drug and alcohol
dependence. 2013;133(2):494-501. 2. Benyamina A, Stöver H. Barriers to treatment access and informed patient choice in the treatment of opioid dependence in Europe. Editorial Board.
2012.
LOW RETENTION
IN TREATMENT
RISK OF MISUSE AND DIVERSION OF
SUBSTITUTION TREATMENT
HIGH BURDEN OF DAILY
ADMINISTERED DOSING OF OAT
PATIENTS STILL USE ILLICIT OPIOIDS
WHILST IN TREATMENT
Treatment limitations constitute important barriers for successful
treatment outcomes1,2
CHALLENGES ASSOCIATED WITH CURRENT TREATMENT OPTIONS INCLUDE:

9. Buvidal® weekly and monthly long-acting individualized
treatment for opioid dependence
Buvidal® Summary of Product Characteristics (SmPC). September 2020.
Buvidal® monthly
64 mg, 96 mg, 128 mg preparations
(356 mg/mL buprenorphine with N-Methyl pyrrolidine [NMP] as solvent)
Buvidal® weekly
8 mg, 16 mg, 24 mg, 32 mg preparations
(50 mg/mL buprenorphine with Ethanol anhydrous as solvent)

10. Administering CAM2038
8
injection areas
Injections should be rotated between sites in the buttock, thigh, abdomen, and
upper arm with a minimum of eight weeks before re-injecting a previously used
injection site. Injections on the waistline or within 5 cm of the navel should be
avoided.
Buvidal® Summary of Product Characteristics (SmPC). September 2020.

11. Dose conversion for switching between CAM2038 and
sublingual buprenorphine
Dose of daily SL BPN Dose of CAM2038 weekly Dose of CAM2038 monthly
2–6 mg 8 mg –
8–10 mg 16 mg 64 mg
12–16 mg 24 mg 96 mg
18–24 mg 32 mg 128 mg
Camurus Buvidal® Summary of Product Characteristics (SmPC). Camurus AB, Sweden. November 2018.
SL BPN = sublingual buprenorphine

12. WHERE IS THE EVIDENCE?

14. Blockade of opioid effects
• Rapid and sustained blockade of drug liking from the first CAM2038 dose
CAM2038 weekly 24 mg
CAM2038 weekly 32 mg
0
40
50
70
80
100
Peak
Score
(mm)
0 6 18
Hydromorphone (mg, IM)
0 6 18 0 6 18 0 6 18 0 6 18
Pre-treatment
Qualification (Days 1-3) (Days 4-6) (Days 8-10) (Days 11-13)
CAM2038 weekly
injection 1
60
90
11 pts difference
Prespecified complete blocking
criteria
Neutral
Strong Disliking
Strong Liking
CAM2038 weekly
injection 2
“At this moment, my liking for this
drug is”
Walsh SL et al. JAMA Psych 2017; 74: 894-902.
IM = intramuscular

15. Suppression of withdrawal from Day 1
• Clinical opiate withdrawal scale (COWS) scores
0
3
6
9
12
48
Total
COWS
Score
BL 1 2
Treatment Days
3 4 5 6 7 8 9 10 11 12 13 14
CAM2038 weekly 24 mg
CAM2038 weekly 32 mg
weekly injection 2
weekly injection 1
Withdrawal COWS Score
– <5
Mild 5-12
Moderate 13-24
Moderate to
Severe
25-36
Severe >36
Data from Phase 2 study (HS-13-478), N=47
Walsh SL et al. JAMA Psych 2017; 74: 894-902.

16. WHERE IS THE EVIDENCE?

18. CAM2038 provides sustained suppression of withdrawal and cravings
Total
COWS
score
Treatment week
Buvidal® 24 mg
(n = 22)
Opioid withdrawal Opioid cravings: “Since your last scheduled assessment visit, indicate your
worst or strongest need to use opioids”
Treatment week
Clinical opiate withdrawal scale (COWS)
Withdrawal COWS score
– < 5
Mild 5–12
Moderate 13–24
Moderate to severe 25–36
Severe < 36
VAS
score,
mm
Buvidal®
(n = 213)
SL-BPN/NX
(n = 215)
Buvidal®
(n = 213)
SL-BPN/NX
(n = 215)
COWS = clinical opiate withdrawal scale, SL BPN/NX = sublingual buprenorphine/naloxone, VAS = visual analog scale
Lofwall M et a. JAMA Int. Med. 2018,178; 764-773 & Data on file Camurus AB
Visual analog scale (VAS) score
Need/desire to use VAS score
No need to use 0
Strongest need to use 100

19. Retention during 24 weeks study with
CAM2038
69.0% of participants randomized
to Buvidal® and 72.6%
randomized to SL-BPN/NX
completed the 24-week study
SL BPN/NX = sublingual buprenorphine/naloxone
Lofwall M et al. JAMA Int. Med. 2018,178; 764-773 & Data on file Camurus AB

20. Safety profile
Study group, no. (%) of participants
Adverse event characteristic SL-BPN/NX (n = 215) Buvidal® (n = 213) All (n = 428)
≥ 1 Any 119 (55.3%) 128 (60.1%) 247 (57.7%)
≥ 1 Drug-related 64 (29.8%) 70 (32.9%) 134 (31.3%)
≥ 1 Severe 15 (7.0%) 6 (2.8%) 21 (4.9%)
Non-fatal serious 13 (6.0%) 5 (2.3%) 18 (4.2%)
Deaths* 0 1 (0.5%)* 1 (0.2%)*
Hospitalisations 12 (5.6%) 3 (1.4%) 15 (3.5%)
Drug overdoses 5 (2.3%) 0 5 (1.2%)
Led to discontinuation of treatment 3 (1.4%) 7 (3.3%) 10 (2.3%)
Occurred in ≥ 5% of participants
Injection site pain 17 (7.9%) 19 (8.9%) 36 (8.4%)
Headache 17 (7.9%) 16 (7.5%) 33 (7.7%)
Constipation 16 (7.4%) 16 (7.5%) 32 (7.5%)
Nausea 17 (7.9%) 15 (7.0%) 32 (7.5%)
Injection-site pruritus 13 (6.0%) 13 (6.1%) 26 (6.1%)
Injection-site erythema 12 (5.6%) 12 (5.6%) 24 (5.6%)
Urinary tract infection 10 (4.7%) 11 (5.2%) 21 (4.9%)
Insomnia 6 (2.8%) 12 (5.6%) 18 (4.2%)
*One patient died as a result of being hit by a car.
Lofwall M et al. JAMA Int. Med. 2018,178; 764-773.
SL BPN/NX = sublingual buprenorphine/naloxone

21. WHERE IS THE EVIDENCE ?

22. Long-term safety data – Adverse event profile
Overall Safety Population
Category
Transferred from
SL BPN (n, (%))
N=190
New to BPN
treatment (n, (%))
N=37
Overall (n, (%))
N=227
A least 1 AE 131 (68.9) 12 (32.4) 143 (63.0)
At least 1 drug-related AE 58 (30.5) 2 (5.4) 60 (26.4)
Injection site AE 43 (22.6) 2 (5.4) 45 (19.8)
Non-injection site AE 23 (12.1) 1 (2.7) 24 (10.6)
AEs leading to study drug discontinuations 3 (1.6) 0 (0) 3 (1.3)
At least 1 SAE 10 (5.3) 2 (5.4) 12 (5.3)
Hospitalisations 9 (4.7) 1 (2.7) 10 (4.4)
At least 1 drug-related SAE 0 (0) 0 (0) 0 (0)
Deaths 0 (0) 0 (0) 0 (0)
AE = adverse event, BPN = buprenorphine, SL BPN = sublingual buprenorphine, TEAE = treatment-emergent adverse event, SAE = serious adverse event
1. Frost M et al. Addiction. 2019;114:1416-1426; 2. Data on file Camurus AB

23. Long-term safety data – Adverse events in ≥5% of
participants
Overall Safety Population
Category
Transferred from
SL BPN, (n, (%))
N=190
New to BPN
treatment, (n, (%))
N=37
Overall, (n, (%))
N=227
TEAEs in ≥5% of participants
Injection site pain 33 (17.4) 2 (5.4) 35 (15.4)
Injection site swelling 25 (13.2) 2 (5.4) 27 (11.9)
Injection site erythema 20 (10.5) 1 (2.7) 21 (9.3)
Headache 18 (9.5) 0 (0) 18 (7.9)
Nasopharyngitis 17 (8.9) 1 (2.7) 18 (7.9)
Nausea 16 (8.4) 0 (0) 16 (7.0)
Vomiting 12 (6.3) 0 (0) 12 (5.3)
Urinary tract infection 9 (4.7) 3 (8.1) 12 (5.3)
BPN = buprenorphine, SL BPN = sublingual buprenorphine, TEAE = treatment-emergent adverse event
Frost M et al. Addiction. 2019;114:1416-1426

24. Retention during 48 weeks study
Frost M et al. Addiction. 2019;114:1416-1426; Data on file, Camurus AB.

25. Percentage of patients with no illicit opioid use by time
point
Data combines patients on weekly and monthly visit schedules. Missing values not imputed. Negative urines with self-reports.
1. Frost M et al. Addiction. 2019;114:1416-1426; 2. Data on file Camurus AB
SL BPN = sublingual buprenorphine

26. Patient satisfaction with CAM2038 compared to previous
sublingual buprenorphine/naloxone
• The study medication compared to my previously prescribed sublingual buprenorphine
treatment is:
Not a validated scale
Data from Month 12 at end of study
1. Frost M et al. Addiction. 2019;114:1416-1426; 2. Abstract presented at the Annual conference of the Society for the Study of Addiction - November 2018 https://www.addiction-ssa.org/knowledge-hub/cam-2038-a-new-liquid-lipid-crystal-depot-buprenorphine-a-dose-ranging-
suite-of-weekly-and-monthly/; 3. Data on file Camurus AB
Patients transferring from
sublingual buprenorphine (N=133)

27. CONCLUSION
Long-acting buprenorphine may provide added value
for people with opioid use disorder in our country
It has many benefits for patients with multiple
treatment failure or resistant to treatment

28. THANK YOU