Dr. Robert Israel reports

SALIX PHARMACEUTICALS ANNOUNCES A PHASE 2 INVESTIGATOR-INITIATED STUDY OF RELISTOR(R) (METHYLNALTREXONE BROMIDE: MNTX) IN PATIENTS WITH RESECTABLE HEAD AND NECK SQUAMOUS CELL CARCINOMA

Bausch Health Companies Inc. is supporting a phase 2 investigator-initiated study (IIS) of Relistor (methylnaltrexone bromide: MNTX) in patients with resectable head and neck squamous cell carcinoma. An IIS is a study that is proposed, developed and conducted by a qualified sponsor external to Bausch Health/Salix which assumes full responsibility for the study.

The clinical study is being led by Dr. Juan P. Cata, MD, at the University of Texas MD Anderson Cancer Center. The trial is designed to evaluate the potential of treating oral cavity squamous cell carcinoma patients with MNTX. It is a prospective, non-randomized pilot proof-of-concept study where patients receive subcutaneous MNTX two weeks preoperatively and two weeks postoperatively.

"The preclinical data and clinical suggestions point to potential activity against cancer," Dr. Robert Israel, MD, senior vice-president, clinical and medical affairs, said. "Having Dr. Cata study this drug in head and neck cancer will shed light on how and if this agent could be further developed as a potential treatment option in neoplastic disease."

Upon completion of the study, participants will be monitored every three months during the first two years. The primary end point is the successful administration of MNTX for two weeks preoperatively and postoperatively without interruption due to adverse events. Secondary end points include tumour viability, proliferation and apoptosis index, objective response rate, survival rates, and patient-reported outcomes.

About Relistor

Relistor (methylnaltrexone bromide) is an opioid antagonist. Relistor tablets and Relistor injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (such as weekly) opioid dosage escalation.

Relistor injection is also indicated for the treatment of OIC in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.

Important safety information

Relistor tablets and injection are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (such as peptic ulcer disease, Ogilvie's syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using Relistor in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (such as Crohn's disease). Monitor for the development of severe, persistent or worsening abdominal pain; discontinue Relistor in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with Relistor and consult their health care provider.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety and yawning, have occurred in patients treated with Relistor. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal.

Avoid concomitant use of Relistor with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

The use of Relistor during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breast-fed infants, advise women that breastfeeding is not recommended during treatment with Relistor. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

A dosage reduction of Relistor tablets and Relistor injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 millilitres/minute as estimated by Cockcroft-Gault). No dosage adjustment of Relistor tablets or Relistor injection is needed in patients with mild renal impairment.

A dosage reduction of Relistor tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child- Pugh Class C) hepatic impairment. No dosage adjustment of Relistor tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of Relistor injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions and dose adjust per prescribing information as may be indicated.

In the clinical studies, the most common adverse reactions were:

OIC in adult patients with chronic non-cancer pain

Relistor tablets (greater than or equal to 2 per cent of Relistor patients and at a greater incidence than placebo): abdominal pain (14 per cent), diarrhea (5 per cent), headache (4 per cent), abdominal distention (4 per cent), vomiting (3 per cent), hyperhidrosis (3 per cent), anxiety (2 per cent), muscle spasms (2 per cent), rhinorrhea (2 per cent) and chills (2 per cent).

Relistor injection (greater than or equal to 1 per cent of Relistor patients and at a greater incidence than placebo): abdominal pain (21 per cent), nausea (9 per cent), diarrhea (6 per cent), hyperhidrosis (6 per cent), hot flush (3 per cent), tremor (1 per cent) and chills (1 per cent).

OIC in adult patients with advanced illness

Relistor injection (greater than or equal to 5 per cent of Relistor patients and at a greater incidence than placebo): abdominal pain (29 per cent) flatulence (13 per cent), nausea (12 per cent), dizziness (7 per cent) and diarrhea (6 per cent).

To report suspected adverse reactions, contact Salix Pharmaceuticals at 1-800-321-4576 or the Food and Drug Administration at 1-800-FDA-1088 or the FDA website.

About Bausch Health Companies Inc.

Bausch Health Companies is a global company whose mission is to improve people's lives with its health care products. It develops, manufactures and markets a range of pharmaceutical, medical device and over-the-counter products, primarily in the therapeutic areas of eye health, gastroenterology and dermatology. Bausch Health is delivering on its commitments as it builds an innovative company dedicated to advancing global health.

We seek Safe Harbor.