Hikma Pharmaceuticals Regulatory News (HIK)

London, April 30, 2021 - Hikma Pharmaceuticals PLC (Hikma), the multinational pharmaceutical company, announces the approval of KLOXXADOTM (naloxone hydrochloride) nasal spray 8mg, by the US Food and Drug Administration (FDA) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, for adult and pediatric patients.

KLOXXADOTM contains twice as much naloxone per spray as Narcan® Nasal Spray 4mg in a ready-to-use nasal spray to reverse the effects of opioid overdose, providing an important new treatment option in addressing the opioid epidemic.

Drug overdose, including most commonly opioid overdose, has been described as the "leading cause of accidental death" in the US today1 - a situation that has been exacerbated by the COVID-19 pandemic2. According to health organizations, widely prescribing and distributing naloxone may play a vital role in the fight against opioid overdose3. With the increasing prevalence of illicitly manufactured synthetic opioids, a higher dose of naloxone may be required to revive a patient4.

In a survey of community organizations to which Narcan® Nasal Spray 4mg had been distributed, 34% of attempted reversals used two or more doses5. Additionally, a separate study published in 2019 found that the percent of overdose-related EMS calls in the US requiring multiple doses of naloxone during 2013-2016 had increased to 21%, representing a 43% increase over those four years6.

"The approval of KLOXXADOTM is an important step in providing patients, friends and family members - as well as the public health community - with an important new option for treating opioid overdose," said Brian Hoffmann, President, Hikma Generics. "As an experienced provider of addiction therapy treatments and a leading producer of nasal sprays in the US, we are pleased to leverage our capabilities to deliver an important new tool in the fight against opioid overdose."

Hikma expects KLOXXADOTM to be available in the second half of 2021.

About Naloxone 

Naloxone hydrochloride is an opioid antagonist that antagonises opioid effects by competing for the same receptor sites. Administration of naloxone hydrochloride reverses the effects of opioids, including respiratory depression, sedation and hypotension. Naloxone has a long history of safe use as the standard of care for reversing opioid overdoses7.

KLOXXADOTM is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, for adult and pediatric patients. KLOXXADOTM is not a substitute for emergency medical care. KLOXXADOTM is intended for immediate administration as emergency therapy in settings where opioids may be present.

KLOXXADOTM is a trademark of Hikma Pharmaceuticals USA Inc.

NARCAN® is a registered trademark of ADAPT Pharma Operations Limited.

[1] https://pubmed.ncbi.nlm.nih.gov/29262202/

2 https://www.wsj.com/articles/the-opioid-crisis-already-serious-has-intensified-during-coronavirus-pandemic-3 1599557401?mod=article_inline

3 https://emergency.cdc.gov/han/2020/han00438.asp

4 https://emergency.cdc.gov/han/2020/han00438.asp

5 2016 FDA Advisory Committee on the Most Appropriate Dose or Doses of Naloxone to Reverse the Effects of Life-threatening Opioid Overdose in the Community Settings, Page 149: https://www.fda.gov/media/100409/download

6 2019 Geiger et. al., Substance Abuse: https://www.tandfonline.com/doi/abs/10.1080/08897077.2019.1640832

7 https://www.fda.gov/consumers/consumer-updates/having-naloxone-hand-can-save-life-during-opioid-overdose

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Hikma Pharmaceuticals PLC

About Hikma(LSE: HIK) (NASDAQ Dubai: HIK) (OTC: HKMPY) (rated BBB-/stable S&P and BBB-/stable Fitch)

Hikma helps put better health within reach every day for millions of people in more than 50 countries around the world. For more than 40 years, we've been creating high-quality medicines and making them accessible to the people who need them. Headquartered in the UK, we are a global company with a local presence across the United States (US), the Middle East and North Africa (MENA) and Europe, and we use our unique insight and expertise to transform cutting-edge science into innovative solutions that transform people's lives. We're committed to our customers, and the people they care for, and by thinking creatively and acting practically, we provide them with a broad range of branded and non-branded generic medicines. Together, our 8,600 colleagues are helping to shape a healthier world that enriches all our communities. We are a leading licensing partner, and through our venture capital arm, are helping bring innovative health technologies to people around the world. For more information, please visit: www.hikma.com

KLOXXADOTM (naloxone hydrochloride) Nasal Spray Important Safety Information

CONTRAINDICATIONS

• Hypersensitivity to naloxone hydrochloride or to any of the other ingredients in KLOXXADOTM

WARNINGS AND PRECAUTIONS

• Risk of Recurrent Respiratory and Central Nervous System Depression

Seek emergency assistance immediately after administration of the first dose and keep the patient under continued surveillance. The duration of action of most opioids may exceed that of KLOXXADO, resulting in a return of respiratory and/or central nervous system depression after an initial improvement in symptoms. Administer additional doses as necessary if the patient is not adequately responding or responds and then relapses back into respiratory depression.

• Risk of Limited Efficacy With Partial Agonists or Mixed Agonist/Antagonists

Reversal of respiratory depression by partial agonists or mixed agonist/antagonists may be incomplete. Larger or repeat doses of naloxone hydrochloride may be required.

• Precipitation of Severe Opioid Withdrawal

Use in patients who are opioid-dependent may precipitate opioid withdrawal characterized by body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness and increased blood pressure. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include convulsion, excessive crying and hyperactive reflexes. Monitor the patient for the development of the signs and symptoms of opioid withdrawal. For more information about management of opioid withdrawal, see the full Prescribing Information.

Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome. In some patients, there was aggressive behavior upon abrupt reversal of an opioid overdose.

Abrupt postoperative reversal of opioid depression after using naloxone hydrochloride may result in nausea, vomiting, sweating, tremulousness, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia and fibrillation, pulmonary edema and cardiac arrest. Death, coma and encephalopathy have been reported as sequelae of these events. These events have primarily occurred in patients who had pre-existing cardiovascular disorders or received other drugs that may have similar adverse cardiovascular effects. Monitor these patients closely in an appropriate healthcare setting.

ADVERSE REACTIONS

In two pharmacokinetic studies, a total of 47 healthy adult volunteers were exposed to a single dose of KLOXXADO, one spray in one nostril.

- The following adverse reactions were reported in two subjects each: abdominal pain, asthenia, dizziness, headache, nasal discomfort, and presyncope.

- Signs of nasal inflammation and nasal congestion were observed

- Serious adverse reactions reported: none

The following most frequently reported events (in decreasing frequency) have been identified primarily during post-approval use of naloxone hydrochloride: withdrawal syndrome, vomiting, nonresponsiveness to stimuli, drug ineffective, agitation, somnolence, and loss of consciousness.

USE IN SPECIFIC POPULATIONS

• Pregnancy

Naloxone may precipitate opioid withdrawal in the pregnant woman and fetus. Careful monitoring is needed until the fetus and mother are stabilized.

• Infants

In situations where the primary concern is for infants at risk for opioid overdose, consider the availability of alternate naloxone-containing products.

For more information, please see the full Prescribing Information and Patient Information, which you can find in the full press release published on our website at https://www.hikma.com/newsroom/#pageRS=1.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/medwatch or call 1-800-FDA-1088.

Distributed by: Hikma Specialty USA Inc., Berkeley Heights, NJ 07922

Document Identification Number: WW40054