TORONTO, Sept. 30, 2014 /CNW/ - Concordia Healthcare Corp. ("Concordia" or the "Company") (TSX: CXR) (OTCQX: CHEHF), a diverse healthcare company focused on legacy pharmaceutical products, orphan drugs, and medical devices for the diabetic population, today announced that its subsidiary, Concordia Pharmaceuticals Inc. ("CPI"), has completed the previously announced acquisition of Zonegran® (zonisamide) for commercialization and sale in the United States, including Puerto Rico.
CPI acquired Zonegran from Eisai Inc. ("Eisai") for US$90 million in cash, plus approximately US$1.3 million for purchased inventory.
"The acquisition of Zonegran for commercialization and sale in the United States and Puerto Rico further diversifies Concordia's growing pipeline of legacy drugs," said Mark Thompson, CEO of Concordia. "In addition, we believe that Zonegran will provide sustainable revenue going forward."
Zonegran is an antiepileptic drug (AED) originally created by Dainippon Pharmaceutical Co., Ltd. (currently Sumitomo Dainippon Pharma Co., Ltd.). Zonegran was first approved by the U.S. Food and Drug Administration in March 2000 as an adjunctive therapy in the treatment of partial seizures in adults with epilepsy. It is available in 25mg and 100mg capsules. Zonegran is a registered trademark of Sumitomo Dainippon Pharma Co., Ltd.
Management paid for the acquisition through debt financing. Accordingly, General Electric Capital Corporation ("GE Capital") has provided an incremental senior secured credit facility of up to $95,000,000 (the "Incremental Term Loan") by way of an amendment and restatement of the existing credit agreement among GE Capital, Healthcare Financial Services, as agent, the Company, as borrower, certain credit parties party thereto, and certain lenders party thereto, dated May 14, 2014.
All obligations of the Company under the Incremental Term Loan are secured by existing first priority perfected security interests in the assets of the Company and the assets of its subsidiaries.
Torreya Partners acted as financial advisor to Concordia.
Concordia is a diverse healthcare company focused on legacy pharmaceutical products, orphan drugs, and medical devices for the diabetic population. The Company's pharmaceutical business consists of ADHD-treatment Kapvay® (clonidine extended release tablets), head lice treatment Ulesfia® (benzyl alcohol) Lotion, asthma-related medication Orapred ODT® (prednisolone sodium phosphate orally disintegrating tablets), irritable bowel syndrome treatment Donnatal® (belladonna alkaloids, phenobarbital), and Zonegran® (zonisamide) for treatment of partial seizures in adults with epilepsy. Concordia's Specialty Healthcare Distribution (SHD) division, Complete Medical Homecare, distributes medical supplies targeting diabetes and related conditions. Concordia's orphan drug division, Pinnacle, markets PHOTOFRIN® in the United States.
Concordia operates out of facilities in Oakville, Ontario; Lenexa, Kansas (near Kansas City, Missouri); Chicago, Illinois; Bridgetown, Barbados; and Charlottesville, Virginia.
About Eisai Inc.
At Eisai Inc., human health care is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to help address unmet medical needs. We are a fully integrated pharmaceutical business with discovery, clinical, manufacturing and marketing capabilities. Our key areas of commercial focus include oncology and specialty care. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
Eisai Inc. has affiliates that are part of a global product creation organization that includes R&D facilities in Massachusetts, New Jersey, North Carolina and Pennsylvania, as well as a global demand chain organization that includes manufacturing facilities in Maryland and North Carolina.
Notice regarding forward-looking statements:
This release includes forward-looking statements regarding Concordia and its business, which may include, but is not limited to, statements with respect to the acquisition, the impact of the acquisition on Concordia's financial performance (including with respect to its revenues), Concordia's growth and other factors. Often, but not always, forward-looking statements can be identified by the use of words such as "plans", "is expected", "expects", "scheduled", "intends", "contemplates", "anticipates", "believes", "proposes" or variations (including negative and grammatical variations) of such words and phrases, or state that certain actions, events or results "may", "could", "would", "might" or "will" be taken, occur or be achieved. Such statements are based on the current expectations of Concordia's management, and are based on assumptions and subject to risks and uncertainties. Although Concordia's management believes that the assumptions underlying these statements are reasonable, they may prove to be incorrect. The forward-looking events and circumstances discussed in this release may not occur by certain specified dates or at all and could differ materially as a result of known and unknown risk factors and uncertainties affecting Concordia, including risks regarding the pharmaceutical industry, the failure to obtain regulatory approvals, economic factors, market conditions, the equity markets generally, risks associated with growth and competition, risks associated with the acquisition and many other factors beyond the control of Concordia. Although Concordia has attempted to identify important factors that could cause actual actions, events or results to differ materially from those described in forward-looking statements, there may be other factors that cause actions, events or results to differ from those anticipated, estimated or intended. No forward-looking statement can be guaranteed. Except as required by applicable securities laws, forward-looking statements speak only as of the date on which they are made and Concordia undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, or otherwise.
Indication for Zonegran
ZONEGRAN is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.
Important Safety Information about Zonegran
ZONEGRAN is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide.
Potentially Fatal Reactions to Sulfonamides: Fatalities have occurred, although rarely, as a result of severe reactions to sulfonamides (zonisamide is a sulfonamide) including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Such reactions may occur when a sulfonamide is re-administered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue zonisamide immediately.
Serious Skin Reactions
Consideration should be given to discontinuing ZONEGRAN in patients who develop an otherwise unexplained rash. If the drug is not discontinued, patients should be observed frequently. Seven deaths from severe rash [i.e. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)] were reported in the first 11 years of marketing in Japan.
Serious Hematologic Events
Two confirmed cases of aplastic anemia and one confirmed case of agranulocytosis were reported in the first 11 years of marketing in Japan, rates greater than generally accepted background rates. There were no cases of aplastic anemia and two confirmed cases of agranulocytosis in the US, European, or Japanese development programs. There is inadequate information to assess the relationship, if any, between dose and duration of treatment and these events.
Oligohidrosis and Hyperthermia in Pediatric Patients
Oligohidrosis, sometimes resulting in heat stroke and hospitalization, is seen in association with zonisamide in pediatric patients. The practitioner should be aware that the safety and effectiveness of zonisamide in pediatric patients have not been established and that zonisamide is not approved for use in pediatric patients.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including Zonegran, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Zonisamide causes hyperchloremic, non-anion gap, metabolic acidosis (i.e., decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis). This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of zonisamide on carbonic anhydrase. Generally, zonisamide-induced metabolic acidosis occurs early in treatment, but it can develop at any time during treatment. Metabolic acidosis generally appears to be dose-dependent and can occur at doses as low as 25 mg daily. The relatively high frequencies of varying severities of metabolic acidosis observed in one study of pediatric patients (compared to the frequency and severity observed in various clinical trial development programs in adults) suggest that pediatric patients may be more likely to develop metabolic acidosis than adults.
Seizures on Withdrawal
As with other AEDs, abrupt withdrawal of ZONEGRAN in patients with epilepsy may precipitate increased seizure frequency or status epilepticus. Dose reduction or discontinuation of zonisamide should be done gradually.
Women of child bearing potential who are given zonisamide should be advised to use effective contraception. Zonisamide was teratogenic in mice, rats, and dogs and embryolethal in monkeys when administered during the period of organogenesis. A variety of fetal abnormalities, including cardiovascular defects, and embryo-fetal deaths occurred at maternal plasma levels similar to or lower than therapeutic levels in humans. These findings suggest that the use of ZONEGRAN during pregnancy in humans may present a significant risk to the fetus.
Cognitive/ Neuropsychiatric Adverse Events
Use of ZONEGRAN was frequently associated with central nervous system-related adverse events. The most significant of these can be classified into three general categories: 1) psychiatric symptoms, including depression and psychosis, 2) psychomotor slowing, difficulty with concentration, and speech or language problems, in particular, word-finding difficulties, and 3) somnolence or fatigue.
Patients should be cautioned about the possibility of somnolence and fatigue and special care should be taken by patients if they drive, operate machinery, or perform any hazardous task.
Somnolence is commonly reported, especially at higher doses of ZONEGRAN. Zonisamide is metabolized by the liver and eliminated by the kidneys; caution should therefore be exercised when administering ZONEGRAN to patients with hepatic and renal dysfunction.
Among 991 patients treated during the development of ZONEGRAN, 40 patients (4.0%) with epilepsy receiving ZONEGRAN developed clinically possible or confirmed kidney stones. The development of nephrolithiasis may be related to metabolic acidosis. The analyzed stones were composed of calcium or urate salts. In general, increasing fluid intake and urine output can help reduce the risk of stone formation, particularly in those with predisposing risk factors. It is unknown, however, whether these measures will reduce the risk of stone formation in patients treated with ZONEGRAN.
Effect on Renal Function
In several clinical studies, zonisamide was associated with a statistically significant 8% mean increase from baseline of serum creatinine and blood urea nitrogen (BUN) compared to essentially no change in the placebo patients. The increase appeared to persist over time but was not progressive; this has been interpreted as an effect on glomerular filtration rate (GFR). There is no information about reversibility, after drug discontinuation, of the effects on GFR after long-term use. ZONEGRAN should be discontinued in patients who develop acute renal failure or a clinically significant sustained increase in the creatinine/BUN concentration. ZONEGRAN should not be used in patients with renal failure (estimated GFR < 50 mL/min) as there has been insufficient experience concerning drug dosing and toxicity.
Sudden Unexplained Death in Epilepsy
During the development of ZONEGRAN, nine sudden unexplained deaths occurred among 991 patients with epilepsy receiving ZONEGRAN for whom accurate exposure data are available. Although this rate exceeds that expected in a healthy population, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with refractory epilepsy not receiving ZONEGRAN. Some of the deaths could represent seizure-related deaths in which the seizure was not observed.
Estimates of the incidence of treatment emergent status epilepticus in ZONEGRAN-treated patients are difficult because a standard definition was not employed. Nonetheless, in controlled trials, 1.1% of patients treated with ZONEGRAN had an event labeled as status epilepticus compared to none of the patients treated with placebo. Among patients treated with ZONEGRAN across all epilepsy studies (controlled and uncontrolled), 1.0% of patients had an event reported as status epilepticus.
The most commonly observed adverse events related to treatment with ZONEGRAN at an incidence of at least 4% greater than placebo were somnolence (17% vs. 7%), anorexia (13% vs. 6%), dizziness (13% vs. 7%), ataxia (6% vs. 1%), agitation/irritability (9% vs. 4%), and difficulty with memory (6% vs. 2%) and/or concentration (6% vs. 2%).
POST MARKETING EXPERIENCE
The following serious adverse reactions are reported voluntarily from a population of uncertain size: acute pancreatitis, rhabdomyolysis, creatine phosphokinase increased. Therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure.
Effects of ZONEGRAN on the pharmacokinetics of other antiepilepsy drugs (AEDs): Zonisamide had no appreciable effect on the steady state plasma concentrations of phenytoin, carbamazepine, or valproate during clinical trials. Zonisamide is not expected to interfere with the metabolism of other drugs that are metabolized by cytochrome P450 isozymes.
Effects of other drugs on ZONEGRAN pharmacokinetics: Drugs that induce liver enzymes increase the metabolism and clearance of zonisamide and decrease its half-life. Concurrent medication with drugs that either induce or inhibit CYP3A4 would be expected to alter serum concentrations of zonisamide.
Drug Interactions with CNS Depressants
Concomitant administration of ZONEGRAN and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of zonisamide to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse events, zonisamide should be used with caution if used in combination with alcohol or other CNS depressants.
Other Carbonic Anhydrase Inhibitors
Concomitant use of ZONEGRAN, a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., topiramate, acetazolamide or dichlorphenamide), may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation. Therefore, if ZONEGRAN is given concomitantly with another carbonic anhydrase inhibitor, the patient should be monitored for the appearance or worsening of metabolic acidosis.
Pregnancy Category C (see WARNINGS, Teratogenicity)
Zonisamide may cause serious adverse fetal effects, based on clinical and nonclinical data. Zonisamide was teratogenic in multiple animal species. ZONEGRAN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Physicians are advised to recommend that pregnant patients taking ZONEGRAN enroll in the NAAED Pregnancy Registry.
Use in Nursing Mothers
Zonisamide is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from ZONEGRAN, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother.
Please see Zonegran®full prescribing information.
SOURCE Concordia Healthcare Corp.