New 24-week clinical study strengthens the evidence of the therapeutic value of Zubsolv® for maintenance treatment of opioid dependence

Uppsala, Sweden – April 22, 2015 - Orexo AB today announced data from a 24-week
clinical trial assessing the long-term safety and efficacy of Zubsolv®
(buprenorphine/naloxone) sublingual tablet (CIII) for the maintenance treatment
of opioid dependence. The results establish that Zubsolv is effective, well
tolerated and demonstrated a safety profile consistent with the product labeling
for sublingual buprenorphine products. In addition less than 1% of the patients
exited the study due to treatment failure, which further underpins the medical
value of Zubsolv. The results also demonstrated an increase of 15% in employment
by the patients participating in the study, which further strengthen the
evidence of the value of effective treatment of opioid dependence for the
society.

“This study reinforces and further highlights the safety and effectiveness of
Zubsolv. Over the course of six months, the safety profile of Zubsolv was
consistent with previous buprenorphine studies and patient symptoms continued to
improve. In addition, we were able to observe the benefits of long-term
treatment with Zubsolv on work productivity. As patients continued on their path
to recovery, they experienced positive gains for employment status, hours of
work missed, number of hours patients were able to work, productivity, and
impairment of daily activities”, said Michael Sumner, Chief Medical Officer of
Orexo.

Benefits of long-term treatment for patients on their journey to recovery

The primary objective of study OX219-008 was to assess the safety and
tolerability of Zubsolv after an additional 24 weeks of treatment. The results
from Study OX219-008, a multi-center, open-label, 24-week, follow-up study
(N=665), establish that Zubsolv is well tolerated and effective for opioid
dependent patients following six months of treatment. The safety profile was
consistent with the product labeling for sublingual buprenorphine products.

The most common AE was constipation (2.9%) and no individual events were
reported in ≥5% of patients. There was one serious adverse event (SAE) that was
considered treatment-related (depression that started on Day 19 and ceased on
Day 27) and 6 patients discontinued the study with AEs that were considered by
the investigator to be possibly related to treatment.

Retention rates at Week 24 (end of study) were consistent with previous long
-term clinical trials with buprenorphine. The retention rates at Weeks 4, 8, 12,
16, 20, and 24 (EOS) were 84.7%, 72.6%, 63.9%, 57.6%, 50.1%, and 43.9%,
respectively. Opioid cravings were assessed on a 100 point VAS where 0
represented “no cravings” and 100 represented “the most intensive craving” the
patient had ever had. Craving scores continued to improve during the extension
study. At baseline of the parent studies before treatment was initiated, the
mean opioid craving score was 70.8 and, by Week 24, the mean score had been
improved to 10.9 in patients who completed the study.

Health Economic Outcomes were assessed using the Work Productivity and Activity
Impairment Questionnaire: Specific Health Problem assessment (WPAI:SHP). The
WPAI:SHP assessed 7 items related to work productivity and impairment associated
with opioid dependence. By the end of the study in week 24, 15% more patients
were currently employed as compared to the parent study baseline. In addition,
patients reported missing 4.8 fewer hours of work per week on average due to
their opioid dependence. Mean hours actually worked per week increased by 4.6
hours per week from baseline. Patients also reported improvements in the degree
to which their opioid dependence affected their productivity and daily
activities.

Study OX219-008 was an extension of the ISTART (Study 006) and Study 007.
Results from both of the parent studies have previously been released and can be
found under the following link (http://www.orexo.com/en/Investor-Relations/Press
-releases/?guid=899375). The ISTART study showed Zubsolv was as effective as
Suboxone® Film and more than 70 percent preferred Zubsolv after being exposed to
both Zubsolv and Suboxone Film.

“The results of this extension study represent another addition to the already
robust evidence base supporting Zubsolv as an effective and well tolerated
maintenance treatment for patients struggling with opioid dependence. Zubsolv
treatment supports opioid addicted patients in gaining control over their life
and improves their ability to function in society, as evidenced by the higher
employment rates at the end of the observation period concurrent with the
demonstrated reduction in opioid cravings. Orexo’s investments in this follow-up
study, and in planned future studies, demonstrate our continued commitment to
advancing the treatment of opioid dependence for the patients suffering from
this disease and providing effective and well tolerated therapies for physicians
who treat them”, said Nikolaj Sørensen, Chief Executive Officer of Orexo.

For further information, please contact:
Nikolaj Sørensen, President and CEO
Tel: +46 (0)703-50 78 88, E-mail: ir@orexo.com

About Study OX219-008
Study OX219-008 was a multi-center, open-label, extension study in opioid
dependent patients who had completed studies OX219-006 (ISTART) or OX219-007 to
assess safety and efficacy for maintenance treatment of opioid dependence with
Zubsolv. The primary objective was to assess the safety and tolerability of
Zubsolv. Secondary objectives included retention in treatment, treatment effect
on opioid withdrawal symptoms and opioid cravings, quality of life (QoL) and
health economic outcomes (HEOs). Six hundred and sixty five patients entered the
extension study (475 from the ISTART trial, 190 from Study 007).

The total study period for each patient was up to approximately 24 weeks from
the Day 1 visit to the Week 24 (end of study [EOS]) visit. All patients included
in this extension study had previously received at least 22 days of
buprenorphine therapy in the parent studies. No treatment adjuncts were mandated
during the study (e.g. counseling, psychosocial support, participation in
12‑step programs). Study 008 included 7 treatment visits where the first visit
was the same day as the last study day in the parent studies (ISTART and OX219
-007) with follow-up study visits every 4 weeks. Patients were maintained on the
same dose of Zubsolv used in the previous studies. Patients who received
Suboxone® Film on day 22 in the ISTART trial were switched to a corresponding
dose of Zubsolv on Day 1. Zubsolv was individually titrated between 5.7/1.4 mg
and 17.1/4.2 mg to a dose that relieved cravings and opioid withdrawal symptoms
with minimal side effects. Dose adjustments were performed throughout the study
as needed.

About the ISTART Trial
The ISTART Trial was a randomized, non-inferiority, multicenter study to assess
early treatment efficacy of Zubsolv tablet versus Suboxone Film and to explore
switching between treatments. The primary endpoints were retention in treatment
at Day 15 and Day 3. Secondary efficacy assessments included scores on the COWS
and SOWS, and opioid cravings VAS, CGI and PGI improvement from baseline, and
switching between Zubsolv tablet and Suboxone Film. Seven hundred and fifty
eight opioid dependent adult subjects were randomized. On days 1 and 2, patients
received a blinded, fixed dose of Zubsolv (5.7/1.4 mg and 5.7/1.4 or 11.4/2.8
mg, respectively) or generic buprenorphine monotherapy (8 mg and 8 or 16 mg,
respectively). On Day 3, the patients on generic buprenorphine were switched to
Suboxone Film and patients in the Zubsolv tablet arm continued to receive
Zubsolv. Stabilization doses were titrated to a maximum daily dose of 17.1/4.2
mg and 24/6 mg for Zubsolv tablet and Suboxone Film, respectively, based upon
clinical symptoms.

About Zubsolv
Zubsolv (buprenorphine/naloxone) sublingual tablet (CIII) was approved by the
U.S. Food and Drug Administration (FDA) on July 3, 2013, for maintenance
treatment of opioid dependence and should be used as part of a comprehensive
treatment plan, which includes counseling and psychosocial support. Treatment
should be initiated under the direction of physicians who are certified under
the Drug Addiction Treatment Act of 2000, and who have been assigned a unique
identification number (“X” number).

Zubsolv sublingual tablets can be abused in a manner similar to other opioids,
legal or illicit. Clinical monitoring appropriate to the patient’s level of
stability is essential. Liver function tests should be monitored before and
during treatment. Children who take Zubsolv sublingual tablets can have severe,
possibly fatal, respiratory depression. Emergency medical care is critical.
Zubsolv sublingual tablets should be kept out of the sight and reach of
children.

Adverse events commonly observed with the sublingual administration of
buprenorphine/ naloxone sublingual tablets during clinical trials and post
-marketing experience are headache, nausea, vomiting, hyperhidrosis,
constipation, signs and symptoms of withdrawal, insomnia, pain and peripheral
edema.

Further information on Zubsolv can be found at www.zubsolv.com.

Suboxone is a registered trademark of Reckitt Benckiser Healthcare (UK) Ltd.

About Orexo
Orexo is a specialty pharmaceutical company commercializing its proprietary
product Zubsolv® for maintenance treatment of opioid dependence in the US.
Zubsolv is an advanced formulation of buprenorphine and naloxone using Orexo’s
unique knowledge and expertise in sublingual drug delivery. R&D focuses on
reformulation of known substances to new improved products that meet great unmet
medical needs by using its patented proprietary technologies. Orexo’s share is
listed on Nasdaq Stockholm Exchange Mid Cap (STO: ORX) and is available as ADRs
on OTCQX (ORXOY) in the US. Orexo’s global headquarters and R&D are based in
Uppsala, Sweden. www.orexo.com

Orexo AB (publ) discloses the information provided herein pursuant to the
Financial Instruments Trading Act. The information was submitted for publication
at 9:00 am CET on April 22, 2015.