Date: 2018-09-20
Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Vabomere®, formerly known as Carbavance®
Compound: meropenem-vaborbactam
Therapeutic area: Infectious diseases
Action mechanism:
- antibiotic. Vabomere™ (formerly also known as Carbavance) is a fixed-dose combination of the carbapenem, meropenem, and the novel beta-lactamase inhibitor, vaborbactam. The combination is being developed to treat serious gram-negative infections, such as cUTI, including those infections caused by bacteria resistant to currently available carbapenems.
- Vabomere’s development has been supported by a cost-share contract with the Biomedical Advanced Research and Development Authority (BARDA). Ir has been designated by the FDA as a Qualified Infectious Disease Product (QIDP), as authorized under the GAIN Act. It was also granted Fast Track status by the FDA for the treatment of cUTI and pyelonephritis. QIDP designation also provides for additional market exclusivity, if approved.
- In January 2018, The Medicines Company announced the closing of the sale of its infectious disease business unit to Melinta Therapeutics for consideration consisting of $215 million of guaranteed cash, approximately 3.3 million shares of Melinta common stock, tiered royalty payments of 5% to 25% on worldwide net sales of Vabomere™, Orbactiv® and Minocin® IV, and the assumption by Melinta of all royalty, milestone and other payment obligations relating to those products.
Company: Rempex Pharmaceuticals (USA - CA) Melinta Therapeutics (USA - CT)
Disease: complicated urinary tract infections (cUTI), including a type of kidney infection, pyelonephritis, ca used by specific bacteria
Latest news:
- • On September 20, 2018, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation for Vabomere® (meropenem trihydrate/vaborbactam), a new treatment option against the following infections in adults:
- Complicated urinary tract infection, including pyelonephritis, a sudden and severe infection causing the kidneys to swell and which may permanently damage them;
- Complicated intra-abdominal infection; Hospital-acquired pneumonia, including ventilator associated pneumonia;
Bacteria in the blood associated with any of the infections listed above;
- Infections due to aerobic Gram-negative organisms in adults with limited treatment options.
- The CHMP’s opinion will be reviewed by the European Commission (EC), which is expected to make a final decision regarding marketing authorization within 67 days of receiving the CHMP opinion. If approved by the EC, marketing authorization for Vabomere will be granted in all 28 countries of the European Union, Norway, Iceland and Liechtenstein. Milestone payment obligations related to Vabomere’s European approval would not take effect until marketing authorization is granted by the EC.
- The CHMP opinion was supported by data from the TANGO clinical program, including data from TANGO-1, a Phase III, multi-center, randomized, double-blind, double-dummy study to evaluate the efficacy, safety and tolerability of Vabomere compared to piperacillin-tazobactam in the treatment of cUTI, including acute pyelonephritis, in adults, as well as TANGO-2, a multi-center, randomized, open-label clinical trial of Vabomere versus “best available therapy” in subjects with known or suspected carbapenem-resistant Enterobacteriaceae (CRE).
- • On August 3, 2018, Melinta Therapeutics announced that the Centers for Medicare & Medicaid Services (CMS) has granted a new technology add-on payment (NTAP) for Vabomere™ (meropenem and vaborbactam) when administered in the hospital inpatient setting. The NTAP program will provide hospitals with a payment, in addition to the standard-of-care Diagnostic Related Group (DRG) reimbursement, of up to 50% of the cost of Vabomere for a period of two to three years, effective in the 2019 fiscal year starting on October 1, 2018. CMS has assigned a maximum payment of $5,544.00 for a Medicare patient treated with Vabomere. Over 80% of Vabomere’s current and projected utilization among all patients is in the hospital inpatient setting.
- In the final rule concerning Hospital Inpatient Prospective Payment Systems and Fiscal Year 2019 Rates, CMS stated that “Vabomere is a novel, first-in-class beta-lactamase inhibitor [that] helps to protect the meropenem from degradation by certain beta-lactamases, such as KPC. Additionally, results from the TANGO II study demonstrate better outcomes regarding 28-day all-cause mortality taking into account prior antibiotic failures (Vabomere patients (5.3 percent) versus best-available therapy (BAT) patients (33.3 percent), p = 0.03), as well as decreases nephrotoxicity (Vabomere 11.1 percent versus BAT 24.0 percent). Therefore, based on the above, we believe that Vabomere represents a substantial clinical improvement.”
- • On August 29, 2017, the FDA approved Vabomere, formerly Carbavance®, (meropenem-vaborbactam) for adults with complicated urinary tract infections (cUTI), including a type of kidney infection, pyelonephritis, ca used by specific bacteria. The safety and efficacy of Vabomere were evaluated in a clinical trial with 545 adults with cUTI, including those with pyelonephritis. At the end of intravenous treatment with Vabomere, approximately 98 percent of patients treated with Vabomere compared with approximately 94 percent of patients treated with piperacillin/tazobactam, another antibacterial drug, had cure/improvement in symptoms and a negative urine culture test.
- Approximately seven days after completing treatment, approximately 77 percent of patients treated with Vabomere compared with approximately 73 percent of patients treated with piperacillin/tazobactam had resolved symptoms and a negative urine culture.
- The most common adverse reactions in patients taking Vabomere were headache, infusion site reactions and diarrhea. Vabomere is associated with serious risks including allergic reactions and seizures. Vabomere should not be used in patients with a history of anaphylaxis, a type of severe allergic reaction to products in the class of drugs called beta-lactams.
- • On July 25, 2017, The Medicines Company announced that both U.S. and European regulatory authorities have accepted, Vabomere as the U.S. and European trade name for meropenem-vaborbactam, assuming marketing applications are approved. Previously, meropenem-vaborbactam was commonly referred to as “Carbavance.”
- • On February 21, 2017, The Medicines Company announced that the FDA has accepted for priority review its new drug application (NDA) filing for Carbavance® (meropenem-vaborbactam) for the treatment of complicated urinary tract infections (cUTIs). The FDA does not currently plan to hold an advisory committee meeting to discuss the application.
- The NDA filing is based on results from the pivotal Phase III TANGO 1 clinical trial in patients with cUTIs. As previously announced, the TANGO 1 trial met both FDA and European Medicines Agency (EMA) pre-specified primary endpoints. Carbavance also demonstrated statistical superiority over piperacillin-tazobactam with overall success in 98.4% of patients. Supporting the NDA are interim data from the ongoing TANGO 2 Phase III trial, which compares the safety, tolerability and efficacy of Carbavance with best available therapy in patients with selected serious infections due to confirmed or suspected carbapenem-resistant Enterobacteriaceae. The TANGO 2 trial is ongoing and the Company expects results to be available before the end of the third quarter of 2017.
- • On April 11, 2016, The Medicines Company announced that the FDA has granted Fast Track Designation to the investigational agent Carbavance® (meropenem-vaborbactam) for the treatment of complicated urinary tract infections (cUTI).
- • In January 2014 , the FDA designated Carbavance® as a Qualified Infectious Disease Product (QIDP) for cUTIs, intra-abdominal infections, HABP/VABP, and febrile neutropenia. The QIDP designation provides Carbavance® priority review by the FDA , eligibility for the FDA's "fast track" status, and an additional five years of exclusivity upon approval.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-08-29
UE authorization:
Favourable opinion UE: 2018-09-20
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
