Endocarditis, Bacterial

Pictured: Facade of the FDA's office in Maryland/iStock, Grandbrothers Basilea Pharmaceutica received FDA approval Wednesday for its antibiotic Zevtera (ceftobiprole medocaril sodium for injection) in adults with Staphylococcus aureus bloodstream infections and two other indications, marking the end of a 15-year odyssey. The authorization covers the use of Zevtera in adults with Staphylococcus aureus bloodstream infections (SAB), including those with right-sided infective endocarditis and acute bacterial skin and skin structure infections, as well as adult and pediatric patients three months to less than 18 years old with community-acquired bacterial pneumonia (CABP). Peter Kim, director of the FDA’s Division of Anti-Infectives, said in a statement that the approval will “provide an additional treatment option for a number of serious bacterial infections.” In particular, Vance Fowler, professor in the departments of medicine and molecular genetics and microbiology at the Duke University School of Medicine, noted there are limited treatments for SAB, a condition with a high mortality rate that causes substantial morbidity. The FDA approved the beta-lactam antibiotic after seeing results from three clinical trials that enrolled between 390 and 679 participants. The studies showed Zevtera has similar efficacy to comparator drugs in the three adult populations. The FDA relied on the adult CABP trial and a study in 138 pediatric subjects to inform the approval in children with pneumonia. Basilea partnered with Johnson & Johnson to develop the molecule in 2005 but the program ran into regulatory problems. The FDA hit J&J with a warning letter over clinical trials of ceftobiprole and rejected a filing for approval in 2009. Basilea regained the asset, plus compensation for lost payments, in 2010 and brought it to market with partners outside the U.S. The Swiss drugmaker had its own issues, notably a delay to the FDA submission. The FDA approval gives Zevtera 10 years of market exclusivity, starting now, and Basilea is looking for a partner to commercialize the drug. The company had planned to find a commercial partner for the U.S. market before winning FDA approval. Basilea is aiming to complete the process around mid-year to allow it to “explore fully all potential partnering opportunities,” CFO Adesh Kaul said in a statement. Kaul added that Basilea is taking “preparatory steps to shorten the launch timelines, once we have entered into a commercialization partnership.” Basilea CEO David Veitch told investors on an earnings call in February 2024 that the company was in talks with “a few potential partners.” Veitch added that the goal is “to secure an appropriate participation over the lifetime of the product.” That goal is informing the deal structure that Basilea wants to secure. “We want to participate over the entire 10-year period,” Veitch said. “The focus is, therefore, more on having an appropriate royalty rate, having milestones as the product is commercialized. We’re not necessarily looking at front-loading the transaction.” Basilea reported CHF 150 million ($166 million) in revenues related to Cresemba and Zevtera last year, up 23% compared to 2022. The company expects sales to rise by 20% this year to hit CHF 180 million. Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.

Switzerland-based Basilea Pharmaceutica has finally won U.S. FDA approval for its broad-spectrum cephalosporin intravenous antibiotic — in three indications. Ceftobiprole, branded Zevtera, is now approved in the U.S.for the treatment of adult patients with Staphylococcus aureus bloodstream infections (SAB), adult patients with acute bacterial skin and skin structure infections (ABSSSI) and for adult and pediatric patients with community-acquired bacterial pneumonia (CABP). The SAB indication, which includes those with right-sided infective endocarditis, is especially notable, given the current lack of treatments. These bloodstream infections arecaused by methicillin-susceptible and methicillin-resistant isolates, MSSA and MRSA. The approvals are a long-fought win for Zevtera, which will now have 10 years of market exclusivity in the U.S. after a regulatory journey that has lasted more than a decade. Ceftobiprole was first approved in Canada in 2008 for the treatment of complicated skin and soft tissue infections. It has since notched approvals throughout Europe for patients with hospital-acquired bacterial pneumonia (HABP) and CABP. Basilea says it has license and distribution agreements for the drug covering more than 80 countries. But the U.S. story has been different. In 2008, the FDA handed Basilea and then copartner, J&J, a CRL for ceftobiprole for the treatment of complicated skin and skin structure infections. The agency recommended additional site audits be conducted. A year later, the partners were handed a second CRL for the same indication, with the FDA then recommending the partners conduct additional clinical studies. In 2014, Basilea attempted to get approval for ceftobiprole for the treatment of pneumonia, but were shot down after the FDA said U.S. approval would require additional phase 3 data. Now, with an FDA approval finally in hand,Basilea is looking for a U.S. partner. "Whilst our initial goal was to have announced a commercial partnership by the time of approval of Zevtera in the US, in order to explore fully all potential partnering opportunities, we now expect to complete the process around mid-year," said Adesh Kaul, Basilea CFO.

Ad hoc announcement pursuant to Art. 53 LR Allschwil, Switzerland, April 04, 2024 Basilea Pharmaceutica Ltd, Allschwil (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today that the US Food and Drug Administration (FDA) approved ZEVTERA® (ceftobiprole medocaril sodium for injection), for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis, and adult patients with acute bacterial skin and skin structure infections (ABSSSI) and for adult and pediatric patients (3 months to less than 18 years old) with community-acquired bacterial pneumonia (CABP). David Veitch, Chief Executive Officer of Basilea, said: “We are excited with the US approval of ZEVTERA. The positive decision by the FDA is a key milestone towards bringing ZEVTERA to patients in the US. ZEVTERA has 10 years of market exclusivity from the date of approval and we believe the US provides the most important global commercial opportunity for the brand.” Dr. Marc Engelhardt, Chief Medical Officer of Basilea, stated: “We are very pleased that the FDA approved ZEVTERA for all three indications that were submitted with the NDA, including a pediatric labelling. This approval is a landmark for ceftobiprole and reflects its broad clinical utility. The indication in adult patients with Staphylococcus aureus bacteremia, including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates, MSSA and MRSA, addresses a real medical need, as current treatment options are limited.” The New Drug Application (NDA) was supported by clinical efficacy and safety data from the phase 3 studies ERADICATE (SAB)1 and TARGET (ABSSSI),2 and a phase 3 study in CABP.3 The ERADICATE study was the largest double-blind randomized registrational study conducted for a new antibiotic treatment in SAB. Vance G. Fowler, Jr., M.D., Professor in the Departments of Medicine and Molecular Genetics & Microbiology at the Duke University School of Medicine and academic lead investigator of the ERADICATE study, commented: “Complicated Staphylococcus aureus infections have a high mortality rate and are associated with substantial morbidity. We need more options for treating these infections, especially if MRSA is involved.” Thomas Holland, M.D., Associate Professor in the Department of Medicine at the Duke University School of Medicine and chair of the data review committee of the ERADICATE study, added: “There is a high medical need in Staphylococcus aureus bacteremia, therefore, the first approval of a therapy for this indication in over 15 years is highly welcome.” Adesh Kaul, Chief Financial Officer of Basilea, added: “As we were moving towards completion of the regulatory review, especially with increasing visibility on the expected label, the external interest for commercial partnering increased. Whilst our initial goal was to have announced a commercial partnership by the time of approval of ZEVTERA in the US, in order to explore fully all potential partnering opportunities, we now expect to complete the process around mid-year. In parallel, we are also taking preparatory steps to shorten the launch timelines, once we have entered into a commercialization partnership.” Basilea’s phase 3 program for ceftobiprole is funded in part with federal funds from the US Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under contract number HHSO100201600002C. Through this partnership, Basilea has been awarded approximately USD 112 million, or approximately 75 percent of the costs related to the SAB and ABSSSI phase 3 studies, regulatory activities and non-clinical work. About ZEVTERA® (ceftobiprole medocaril sodium for injection) Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced generation cephalosporin antibiotic for intravenous administration, with rapid bactericidal activity against a wide range of Gram-positive bacteria, such as Staphylococcus aureus, including methicillin-resistant strains (MRSA), and Gram-negative bacteria.4 In several countries in Europe and beyond, the brand is currently approved and marketed as Zevtera® and Mabelio® for the treatment of adult patients with hospital-acquired bacterial pneumonia (HABP), excluding ventilator-associated bacterial pneumonia (VABP), and for the treatment of community-acquired bacterial pneumonia (CABP). Basilea has entered into license and distribution agreements covering more than 80 countries. In the United States, ZEVTERA is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including right-sided infective endocarditis, and adult patients with acute bacterial skin and skin structure infections (ABSSSI) and for adult and pediatric patients (3 months to less than 18 years old) with community-acquired bacterial pneumonia (CABP). Important US safety information for ZEVTERA (ceftobiprole medocaril sodium for injection) Contraindications ZEVTERA is contraindicated in patients with a known history of severe hypersensitivity to ZEVTERA, or to other members of the cephalosporin class. Warnings and precautions Increased Mortality with Unapproved use in Ventilator-Associated Bacterial Pneumonia (VABP) Patients: The safety and effectiveness of ZEVTERA for the treatment of VABP has not been established and the use of ZEVTERA for VABP is not approved. Hypersensitivity Reactions: Discontinue ZEVTERA if a hypersensitivity reaction occurs, and institute appropriate treatment. Seizures and other adverse central nervous system (CNS) reactions have been associated with the use of ZEVTERA. If seizures or other CNS adverse reactions occur, evaluate patients to determine whether ZEVTERA should be discontinued. Clostridioides difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including ZEVTERA. Evaluate if diarrhea occurs. Adverse reactions SAB (adult patients): The most common adverse reactions occurring in ≥ 4% of adult patients were anemia, nausea, hypokalemia, vomiting, hepatic enzyme and bilirubin increased, diarrhea, blood creatinine increased, hypertension, leukopenia and pyrexia. ABSSSI (adult patients): The most common adverse reactions occurring in ≥ 2% of adult patients were nausea, diarrhea, headache, injection site reaction, hepatic enzyme increased, rash, vomiting, and dysgeusia. CABP (adult and pediatric patients 3 months to less than 18 years of age): Adult Patients: The most common adverse reactions occurring in ≥ 2% of adult patients were nausea, hepatic enzyme increased, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, phlebitis, hypertension and dizziness. Pediatric Patients: The most common adverse reactions occurring in ≥ 2% of pediatric patients were vomiting, headache, hepatic enzyme increased, diarrhea, infusion site reaction, phlebitis and pyrexia. For full US prescribing information, please visit here: About Staphylococcus aureus bacteremia (SAB) Staphylococcus aureus bacteremia (SAB) is a serious bloodstream infection associated with significant morbidity and mortality.5 Complications include concomitant infections such as bone, joint or heart valve infections, persistent bacteremia or bacteremia in patients on dialysis. With a 30-day all-cause mortality of around 20% there is a high medical need for improved therapies for SAB.6 About acute bacterial skin and skin structure infections (ABSSSI) Acute bacterial skin and skin structure infections (ABSSSI) are common infections in the healthcare setting. Staphylococcus aureus is the most common pathogen associated with these infections, which can be difficult to treat if methicillin-resistant Staphylococcus aureus (MRSA) is involved.7 About community-acquired bacterial pneumonia (CABP) Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality worldwide. It is the leading cause of infectious disease-related death in the US.8 About Basilea Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the needs of patients with severe bacterial and fungal infections. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of bacterial infections. In addition, we have preclinical and clinical anti-infective assets in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com. Disclaimer This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning Basilea Pharmaceutica Ltd, Allschwil and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd, Allschwil to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd, Allschwil is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. For further information, please contact: Peer Nils Schröder, PhD Head of Corporate Communications & Investor Relations Basilea Pharmaceutica International Ltd, Allschwil Hegenheimermattweg 167b 4123 Allschwil Switzerland Phone +41 61 606 1102 E-mail media_relations@basilea.com investor_relations@basilea.com This ad hoc announcement can be downloaded from . References ERADICATE study (SAB): ClinicalTrials.gov identifier NCT03138733 T. L. Holland, S. E. Cosgrove, S. B. Doernberg et al. Ceftobiprole for treatment of complicated Staphylococcus aureus bacteremia. New England Journal of Medicine 2023 (389), 1390-1401; DOI: 10.1056/NEJMoa2300220 TARGET study (ABSSSI): ClinicalTrials.gov identifier NCT03137173 J. S. Overcash, C. Kim, R. Keech et al. Ceftobiprole compared with vancomycin plus aztreonam in the treatment of acute bacterial skin and skin structure infections: Results of a phase 3, randomized, double-blind trial (TARGET). Clinical Infectious Diseases 2021 (73), e1507-e1517 CABP study: ClinicalTrials.gov identifier NCT00326287 S. C. Nicholson, T. Welte, T. M. File Jr. et al. A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalization. International Journal of Antimicrobial Agents 2012 (39), 240-246 Summary of Product Characteristics (SmPC) Zevtera: [Accessed: April 03, 2024] A. P. Kourtis, K. Hatfield, J. Baggs et al. Vital signs: Epidemiology and recent trends in methicillin-resistant and in methicillin-susceptible Staphylococcus aureus bloodstream infections – United States. Morbidity and Mortality Weekly Report 2019 (68), 214-219 K. Hamed, M. Engelhardt, M. E. Jones et al. Ceftobiprole versus daptomycin in Staphylococcus aureus bacteremia: a novel protocol for a double-blind, Phase III trial. Future Microbiology 2020 (1), 35-48 J. Edelsberg, C. Taneja, M. Zervos et al. Trends in US hospital admissions for skin and soft tissue infections. Emerging Infectious Diseases 2009 (15), 1516-1518 J. A. Ramirez, T. L. Wiemken, P. Peyrani et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clinical Infectious Diseases 2017 (65), 1807-1812 Attachment Press release (PDF)