02 July 2020
Acacia Pharma Announces US FDA Approval of BYFAVO™ (remimazolam) for injection for the Induction and Maintenance of Procedural Sedation
- BYFAVO 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 is the second Acacia Pharma product approved by the FDA in 2020 and extends its portfolio of new products for anesthesia
This announcement contains inside information for the purposes of Article 7 of the Market Abuse Regulation (EU) No 596/2014.
Cambridge, UK and Indianapolis, US – 2 July 2020: Acacia Pharma Group plc (“Acacia Pharma” or the “Company”) (EURONEXT: ACPH), a commercial stage biopharmaceutical company focused on developing and commercializing novel products to improve the care of patients undergoing serious medical treatments such as surgery, invasive procedures, or chemotherapy, announces that the US Food and Drug Administration (FDA) has approved BYFAVO™ (remimazolam) for injection for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.
Acacia Pharma in-licensed the commercial rights to BYFAVO for the US from Cosmo Pharmaceuticals NV in January 2020. Remimazolam was developed by Paion AG.
The approval of BYFAVO will help to further strengthen Acacia Pharma’s financial resources, as previously announced, the Company will now have access to an additional €25 million debt facility from Cosmo. Acacia Pharma will make a €30 million upfront payment for the license of BYFAVO to Cosmo, triggered by the approval, consisting of €15 million in cash and €15 million in ordinary shares of Acacia Pharma stock. The €10 million of net cash that Acacia Pharma will receive will be available to help fund the US launch of BYFAVO.
“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.”
“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 by 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.
Dr. Jim Phillips, CEO of PAION AG, commented: “The US 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 US 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.”
“BYFAVO is an important addition to the limited selection of drugs available for procedural sedation,” said Acacia Pharma’s Chief Medical Officer, Dr. Gabriel Fox. “BYFAVO demonstrated clear patient benefits in its extensive clinical trial program, offering very rapid onset and offset of action coupled with an incidence of cardio-respiratory and other adverse reactions similar to that seen in patients in the placebo group. We are grateful to all the clinical investigators and patients who made this approval possible through their participation in the development program.”
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. See Important Safety Information at the end of this press release and Prescribing Information.
Acacia Pharma’s first product, BARHEMSYS® (amisulpride injection) was approved by the FDA on 26 February 2020 for the treatment and prevention of postoperative nausea and vomiting (PONV) in adult patients and the company intends to launch both BARHEMSYS and BYFAVO in the US during the second half of 2020.
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.
Acacia Pharma Group plc
Mike Bolinder, CEO
Gary Gemignani, CFO
+44 1223 919760 / +1 317 505 1280
Citigate Dewe Rogerson (Financial PR)
Mark Swallow, Frazer Hall, David Dible
+44 20 7638 9571
About Acacia Pharma
Acacia Pharma is a hospital pharmaceutical company focused on the development and commercialization of new products aimed at improving the care of patients undergoing significant treatments such as surgery, other invasive procedures, or cancer chemotherapy. The Company has identified important and commercially attractive unmet needs in these areas that its product portfolio aims to address.
Acacia Pharma's first product, BARHEMSYS® (amisulpride injection) for postoperative nausea & vomiting (PONV), has been approved by the US FDA, with US launch planned for 2H 2020.
BYFAVO™ (remimazolam) for injection, a very rapid onset/offset IV benzodiazepine sedative is approved in the US for use during invasive medical procedures in adults lasting 30 minutes or less, such as colonoscopy and bronchoscopy. BYFAVO is in-licensed from Cosmo Pharmaceuticals for the US market, and US launch is planned for 2H 2020.
APD403 (intravenous and oral amisulpride), a selective dopamine antagonist for chemotherapy induced nausea & vomiting (CINV) has successfully completed one proof-of-concept and one Phase 2 dose-ranging study in patients receiving highly emetogenic chemotherapy.
Acacia Pharma is based in Cambridge, UK and its US operations are centred in Indianapolis, IN. The Company is listed on the Euronext Brussels exchange under the ISIN code GB00BYWF9Y76 and ticker symbol ACPH.
BYFAVO (remimazolam) for injection is a very rapid onset/offset intravenous benzodiazepine sedative for use during invasive medical procedures in adult patients lasting 30 minutes or less, such as during colonoscopy and bronchoscopy. Approximately 25 million such procedures take place annually in the US, of which around 90% use moderate sedation.
Cosmo in-licensed the US rights to BYFAVO from Paion AG in 2016 and together they have progressed the product candidate through to registration. BYFAVO is now approved in the US and is indicated for the induction and maintenance of procedural sedation in adults lasting 30 minutes or less.
Important Safety Information for BYFAVO™ (remimazolam) Injection
BYFAVO is a benzodiazepine indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.
Important Safety Information
WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS
Personnel and Equipment for Monitoring and Resuscitation
- 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 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-Hypnotics
Concomitant 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.
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 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. 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.
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.
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.
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.
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
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.
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.
Safety and effectiveness in pediatric patients have not been established. BYFAVO should not be used in patients less than 18 years of age.
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.
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.
BYF HCP ISI 07/2020
© 2020 Acacia Pharma Group Plc
BYFAVO™ is a trademark owned or licensed by Cosmo Technologies Ltd.
Forward looking statement
This announcement includes forward-looking statements, which are based on current expectations and projections about future events. These statements may include, without limitation, any statements preceded by, followed by or including words such as "believe", "expect", "intend", "may", "plan", "will", "should", "could" and other words and terms of similar meaning or the negative thereof. Forward-looking statements may and often do differ materially from actual results. These forward-looking statements are subject to risks, uncertainties and assumptions about the Company and its subsidiaries and investments, including, among other things, the development of its business, trends in its operating industry, and future capital expenditures and acquisitions. By their nature, forward-looking statements involve risk and uncertainty because they relate to future events and circumstances. Any forward-looking statements reflect the Company's current view with respect to future events and are subject to risks relating to future events and other risks, uncertainties and assumptions relating to the Group's business, results of operations, financial position, prospectus, growth or strategies and the industry in which it operates. Save as required by law or applicable regulation, the Company and its affiliates expressly disclaim any obligation or undertaking to update, review or revise any forward-looking statement contained in this announcement whether as a result of new information, future developments or otherwise. Forward-looking statements speak only as of the date they are made.