Dublin, Ireland – 2 July 2020: Cosmo Pharmaceuticals announced today that the US Food and Drug Administration (FDA) has approved BYFAVO™ (remimazolam injection) for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less. BYFAVOTM is a very rapid onset/offset IV benzodiazepine sedative for use during invasive medical procedures lasting 30 minutes or less, such as colonoscopy and bronchoscopy. Approximately 25 million such procedures take place annually in the US, of which ~90% use moderate sedation.
BYFAVO™, which was in-licensed from Paion in June 2016, was sub-licensed by Cosmo to Acacia Pharma Group (“Acacia”) (EURONEXT: ACPH) in January 2020 in a deal involving the acquisition by Cosmo of a substantial stake in Acacia. Recently Cosmo made a further investment in Acacia, bringing its stake to 18.53% of the Acacia share capital. As a result of the approval of BYFAVO™ a regulatory milestone of € 15m payable in Acacia shares is now due and Cosmo’s stake in the company will increase to 24.05%. In addition, Cosmo will receive a cash payment of €15m from Acacia which will be used to make a € 15m payment due to Paion AG by Cosmo and a €25 million loan facility which was agreed between Cosmo and Acacia in January 2020 can now be drawn by Acacia.
Acacia obtained FDA approval for BARHEMSYS® in February 2020 and the approval of BYFAVO™ extends Acacia’s portfolio of new products.
“It is gratifying to see how successfully our new strategy is unfolding. We entered into new partnerships with RedHill Biopharma and Acacia before their own main products were approved, taking substantial equity stakes in these companies and integrating our products, Aemcolo® and BYFAVO™, into each so that they could potentially have a more stable and efficient marketing organization. The approval of BYFAVO™ follows the approval of RedHill’s Talicia and Acacia’s BARHEMSYS® and is the third FDA approval in 9 months for products in companies in which we hold an equity stake. We are now looking forward to Acacia Pharma’s transforming BYFAVO™ into a resounding success”, said Alessandro Della Chà, CEO of Cosmo Pharmaceuticals.
“We are very pleased to announce today the approval of BYFAVO™ in the US for procedural sedation in adult patients,” commented Mike Bolinder, Acacia Pharma’s CEO. “This marks the second FDA approval of an Acacia Pharma product since the start of 2020 and another major milestone in our evolution into an integrated hospital pharmaceutical company with strong development and commercialization capabilities. The addition of BYFAVO™ to our product portfolio strengthens our offering to anesthesiologists and enables us to further leverage our commercial infrastructure.
I would like to thank our partners at Paion and Cosmo as well as the Acacia Pharma team and our stakeholders who have enabled us to bring this new and innovative therapeutic to market to address the needs of millions of patients each year undergoing procedures that require sedation.”
Gerard A. Silvestri, MD, MS, Professor of Medicine at the Medical University of South Carolina, Charleston, SC, and past-president of the American College of Chest Physicians, commented: “The approval of remimazolam (BYFAVO™) is very exciting for proceduralists as the field has not seen new sedation medications added to our armamentarium in decades. The drug performed very well in clinical trials, with excellent sedation effect enabling 80-90% of procedures to be completed successfully. The cardio-respiratory safety profile looked very encouraging and there was a rapid return of patients to consciousness enabling them to be discharged in a timely manner.”
Jim Phillips, CEO of PAION AG, commented: “The U.S. marketing approval of BYFAVO™ marks the most significant milestone in PAION’s history, and I congratulate everyone who has played a role in this important achievement. The U.S. is the world’s largest pharmaceutical market, and we are excited to see the product PAION successfully developed being made available to doctors there. We wish Acacia a highly successful market launch in this important market, and we will be supporting their commercialization efforts. We also look forward to remimazolam being rolled out in other countries around the globe as we and our partners work to gain additional marketing approvals.”
The safety of BYFAVO™ was evaluated in three pivotal studies in 969 patients undergoing colonoscopy (two studies) or bronchoscopy (one study), of whom 630 received BYFAVO™. In these studies, the most common adverse reactions (incidence greater than 10%) following BYFAVO™ administration were hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension. The labeling for BYFAVO™ includes a Boxed Warning regarding appropriate training of personnel and equipment that must be available when administering BYFAVO™, during sedation and during the recovery period of the procedure. The Boxed Warning also addresses risks from concomitant use of BYFAVO™ with opioid analgesics and other sedative hypnotics.
It should be noted that BYFAVO™ may not be marketed in the US until the Drug Enforcement Administration has determined its scheduling under the Controlled Substances Act, which is expected to take place within the next few months.
Important Safety Information for BYFAVO™ (remimazolam) Injection
Indications
BYFAVO is a benzodiazepine indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.
| WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS Personnel and Equipment for Monitoring and ResuscitationOnly personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer BYFAVO.Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation.BYFAVO has been associated with hypoxia, bradycardia, and hypotension. Continuously monitor vital signs during sedation and during the recovery period.Resuscitative drugs, and age- and size-appropriate equipment for bag-valve-mask–assisted ventilation must be immediately available during administration of BYFAVO.Risks From Concomitant Use With Opioid Analgesics and Other Sedative-HypnoticsConcomitant use of benzodiazepines, including BYFAVO, and opioid analgesics may result in profound sedation, respiratory depression, coma, and death. The sedative effect of intravenous BYFAVO can be accentuated by concomitantly administered CNS depressant medications, including other benzodiazepines and propofol. Continuously monitor patients for respiratory depression and depth of sedation. |
Contraindication
BYFAVO is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.
Personnel and Equipment for Monitoring and Resuscitation
Clinically notable hypoxia, bradycardia, and hypotension were observed in Phase 3 studies of BYFAVO. Continuously monitor vital signs during sedation and through the recovery period. Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer BYFAVO. Administering p ersonnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation. Resuscitative drugs, and age- and size-appropriate equipment for bag-valve-mask–assisted ventilation must be immediately available during administration of BYFAVO. Consider the potential for worsened cardiorespiratory depression prior to using BYFAVO concomitantly with other drugs that have the same potential (e.g., opioid analgesics or other sedative-hypnotics). Administer supplemental oxygen to sedated patients through the recovery period. A benzodiazepine reversal agent (flumazenil) should be immediately available during administration of BYFAVO.
Risks From Concomitant Use With Opioid Analgesics and Other Sedative-Hypnotics
Concomitant use of BYFAVO and opioid analgesics may result in profound sedation, respiratory depression, coma, and death. The sedative effect of IV BYFAVO can be accentuated when administered with other CNS depressant medications (eg, other benzodiazepines and propofol). Titrate the dose of BYFAVO when administered with opioid analgesics and sedative-hypnotics to the desired clinical response. Continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation. These cardiorespiratory effects may be more likely to occur in patients with obstructive sleep apnea, the elderly, and ASA-PS class III or IV patients.
Hypersensitivity Reactions
BYFAVO contains dextran 40, which can cause hypersensitivity reactions, including rash, urticaria, pruritus, and anaphylaxis. BYFAVO is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.
Neonatal Sedation
Use of benzodiazepines during the later stages of pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) in the neonate. Observe newborns for signs of sedation and manage accordingly.
Pediatric Neurotoxicity
Published animal studies demonstrate that anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of this is not clear. However, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life but may extend out to approximately 3 years of age in humans.
Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks.
Adverse Reactions
The most common adverse reactions reported in >10% of patients (N=630) receiving BYFAVO 5-30 mg (total dose) and undergoing colonoscopy (two studies) or bronchoscopy (one study) were: hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension.
Use in Specific Populations
Pregnancy
There are no data on the specific effects of BYFAVO on pregnancy. Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to benzodiazepines during pregnancy and labor for signs of sedation and respiratory depression.
Lactation
Monitor infants exposed to BYFAVO through breast milk for sedation, respiratory depression, and feeding problems. A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 5 hours after BYFAVO administration.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. BYFAVO should not be used in patients less than 18 years of age.
Geriatric Use
No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, there is a potential for greater sensitivity (eg, faster onset, oversedation, confusion) in some older individuals. Administer supplemental doses of BYFAVO slowly to achieve the level of sedation required and monitor all patients closely for cardiorespiratory complications.
Hepatic Impairment
In patients with severe hepatic impairment, the dose of BYFAVO should be carefully titrated to effect. Depending on the overall status of the patient, lower frequency of supplemental doses may be needed to achieve the level of sedation required for the procedure. All patients should be monitored for sedation-related cardiorespiratory complications.
Abuse and Dependence
BYFAVO has the potential for abuse and physical dependence.
Please click to access full Prescribing Information for BYFAVO.
About Cosmo Pharmaceuticals
Cosmo is a specialty pharmaceutical company focused on developing and commercialising products to treat selected gastrointestinal disorders and improve endoscopy quality measures through aiding the detection of colonic lesions. Cosmo has also developed medical devices for endoscopy and has recently entered into a partnership with Medtronic for the global distribution of GI Genius™ its artificial intelligence device for use in coloscopies and GI procedures. Cosmo has licensed Aemcolo™ to Red Hill Biopharma and is the licensee of BYFAVO™(Remimazolam) for the U.S. for procedural sedation, which it has sub-licensed to Acacia. For additional information on Cosmo and its products please visit the Company’s website: www.cosmopharma.com
Financial calendar
| 2020 Half-Year Results | July 30, 2020 |
| Investora, Zurich | September 23/24, 2020 |
Contact
Niall Donnelly, CFO & Head of Investor Relations
Cosmo Pharmaceuticals N.V.
Tel: +353 1 817 03 70
ndonnelly@cosmopharma.com
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