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38721611000001103

New Medicines

Quofenix (EU), Baxdela (US) Acute bacterial skin and skin structure infections

Information

Quofenix (EU), Baxdela (US)
New molecular entity
Menarini
Melinta

Development and Regulatory status

Launched
Launched
Launched
July 2020
Jul 20Launched in the UK. Pack sizes available are 10 vials for powder and 10 tablets. NHS list price is £615.00 for both formulations [20]
Dec 19Approved in EU. [18]
Oct 19Recommended for EU approval by CHMP - the full indication is "for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the initial treatment of these infections" the proposed authorisation states that "Consideration should be given to official guidance on the appropriate use of antibacterial agents" [17].
Jul 18In 2017, Melinta Therapeutics granted the Menarini Group rights to commercialise delafloxacin in Europe [16].
Jun 18Filed in EU using centralised procedure [15].
Feb 18Will be filed in the EU using the centralised procedure [14].
Jan 18Launched in US for adult patients with acute bacterial skin and skin structure infections (ABSSSI) [13].
Jun 17Approved in US [11].
Jan 17Melinta announces that the FDA has accepted their New Drug Application for Baxdela (oral and IV) in the treatment of acute bacterial skin and skin structure infections (ABSSSI); as it is designated a Qualified Infectious Disease Product, which leads to priority review, the target date for an FDA decision is 19th June 2017 [10].
May 16Melinta Therapeutics plans to file for approval later in 2016 [8].
Oct 15Results from a second PIII study (RX-3341-303) of IV and oral delafloxacin in pts with ABSSSI are expected in the first half of 2016. and filing of a new drug application is anticipated with the US FDA in 2016 [7].

Category

DNA gyrase inhibitor; DNA topoisomerase IV inhibitor; Protein 50S ribosomal subunit inhibitor
In England in 2017/18, there were ~190,000 finished consultant episodes of skin infections including cellulitis, local infections of skin tissues and cutaneous abscess. Up to 10% receive targeted antimicrobial therapy based on antibiotic resistance rates (36 per 100,000 people), rather than empirical therapy.[19]
Acute bacterial skin and skin structure infections
Oral

Trial or other data

Oct 17Results of NCT01811732 published in Journal of Antimicrobial Chemotherapy [12].
Oct 16New Drug application submitted to US FDA for IV and oral delafloxacin for ABSSSI [9].
May 16Top-line data for a PIII study of delafloxacin confirmed its noninferiority to IV vancomycin combination therapy with aztreonam for ABSSSI. The study met both FDA and EMA guidelines [8].
Oct 15Melinta Therapeutics announced complete results from the first of the two PROCEED PIII studies (NCT01811732) of delafloxacin for 660 pts with acute bacterial skin and skin structure infections (ABSSSI). Delafloxacin met the study´s primary endpoint, reduction in lesion size by >20% at 48-72 hours without nonstudy antibiotics or major procedures, which was comparable to the response with vancomycin plus aztreonam. Delafloxacin was also comparable to vancomycin + aztreonam in the study´s secondary endpoint of cure (complete resolution of signs and symptoms at day 14). Delafloxacin-treated pts experienced fewer treatment-emergent adverse events (AEs), and fewer discontinuations due to AEs than pts in the vancomycin + aztreonam arm. The most frequent AEs in the delafloxacin arm were infection, infusion site extravasation, diarrhoea, and nausea. Melinta also provided an analysis of obese pts in this study. Among study participants, 214 pts had a BMI of at >30 kg/m2. More obese pts in the delafloxacin arm achieved cure than in the vancomycin + aztreonam arm [7].
May 15Results for a cohort of obese pts from the first of the PIII PROCEED studies (NCT01811732) announced. A total of 214 obese pts were enrolled and 193 of these pts with a positive clinical response (cured or improved) were assessed for changes in lesion size, signs and symptoms, pain score, and pt-reported HRQL to understand the impact of obesity on response to antibiotic treatment. At late follow-up, pts completed the Extremity Soft Tissue Infection (ESTI) Score, which measures the degree of importance/impairment as assessed by pts of their symptoms, daily functioning, emotional functioning, and social interactions. The investigators assessed that 55% of pts were improved and 26% were cured. Improved pts had a higher ESTI score (greater impairment) than cured pts at late follow-up (46.4 vs 26.3, p=0.029) [6].
Jan 15Melinta Therapeutics announced positive top-line results from the first of two PIII PROCEED studies (NCT01811732) comparing delafloxacin with vancomycin + aztreonam for the treatment of patients with acute bacterial skin and skin structure infections. Delafloxacin met the FDA required primary endpoint of a reduction in the measurement of lesion erythema at the primary infection site at 48-to-72 hours [4].
Feb 14Melinta Therapeutics was previously know as Rib-X
Nov 13NCT01984684 is a PIII, multicentre, randomized, double-blind study of IV and oral delafloxacin (300mg IV twice daily for 3 days then 450mg orally twice daily for up to 10 – 28 doses) vs vancomycin + aztreonam in 660 patients with acute bacterial skin and skin structure infection (cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection) with at least two signs of systemic infection. The primary outcome is objective response of ≥20% reduction in lesion erythema area compared to baseline at 48 to 72 hours after starting treatment as determined by digital measurements of the leading edge. The study starts Dec 13 and is due to complete Jun 15 [3].
May 13NCT01811732 is a PIII, multicentre, randomized, double-blind, active-controlled study of first-line treatment with IV delafloxacin vs vancomycin + aztreonam in 660 patients with acute bacterial skin and skin structure infections. Delafloxacin 300mg will be given every 12 hours for up to 10 to 28 doses. The primary outcome is size of lesion erythema at primary infection at 48 to 72 hours. The study started Apr 13 and is due to complete Sep 14 [2].
May 13The IV formulation of delafloxacin is Captisol-enabled™. Captisol is a patent-protected, chemically modified cyclodextrin designed to optimize solubility and stability of drugs. An oral formulation of delafloxacin is also being developed. The FDA designated delafloxacin as a Qualified Infectious Disease Product (QIDP) for the indications of ABSSSI and community-acquired bacterial pneumonia [2].
Sep 12Rib-X reported additional positive delafloxacin data at ICAAC, including performance against new objective endpoints from FDA, from its completed PIIb study in patients with acute bacterial skin and skin structure infections. The data were presented in 7 posters and a symposium talk (http://www.rib-x.com/investors/press-release_2012_09_11_2.php)
Dec 11Rib-X Pharmaceuticals, Inc. announced positive top-line results from PIIb clinical trial of delafloxacin for the treatment of acute bacterial skin and skin structure infections (ABSSSI), including infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The trial enrolled a total of 256 pts and were randomized into three treatment arms to receive either delafloxacin, 300 mg intravenously every 12 hours, or the recommended dosing for Zyvox, both with and without aztreonam, or vancomycin, both with and without aztreonam. The primary endpoint for the study was the Investigators’ Global Assessment of Cure. Efficacy was evaluated at multiple time points during the study, with a focus on the first five days of administration, through assessments of objective signs and symptoms of infection such as the extent/size of infection, fever, measurement of biochemical markers of inflammation and culture and susceptibility testing of bacterial isolates. Delafloxacin met or exceeded primary and secondary efficacy endpoints evaluated to date in comparison to Zyvox® with and without aztreonam, and vancomycin, with and without aztreonam. The Investigators’ Global Assessment of Cure, delafloxacin demonstrated statistical superiority in comparison to vancomycin (95% Confidence Interval -30.3%, -2.3%; p=0.031). Overall AE rates were statistically equivalent across the study for delafloxacin (74%), Zyvox (72%) and vancomycin (65%). The leading AE associated with delafloxacin was GI disorder with mild to moderate diarrhea as the most common specific event [1].

Evidence based evaluations

Quofenix (EU), Baxdela (US) Community-acquired pneumonia

Information

Quofenix (EU), Baxdela (US)
Licence extension / variation
Menarini
Melinta

Development and Regulatory status

Launched
Launched
Launched
March 2021
Mar 21Licence extension approved in the EU and UK [12].
Feb 21Recommended for EU approval by CHMP - the additional indication is "community- acquired pneumonia (CAP)"; all indications are speciifed to be in adults [11].
Sep 20Application for marketing authorisation for CABP has been submitted to EMA (date not stated) [9].
Oct 19The FDA approves licence extension of Baxdela (delafloxacin) for treatment of community-acquired bacterial pneumonia (CABP) [8].
Jun 19Filed in US for treatment of Community Acquired Bacterial Pneumonia (CABP) in adults. [7]
Jan 19Pipeline indicates NDA being prepared for submission to FDA.[6]
Oct 18Melinta Therapeutics announced intention to submit supplemental NDA to US FDA for CAPB in H1 2019.[5]
Mar 17Has fast track status in the US [2].

Category

DNA gyrase inhibitor; DNA topoisomerase IV inhibitor; Protein 50S ribosomal subunit inhibitor
Annual incidence of CABP is ~1% of the UK adult population (~430,000/year in England); 20-40% of these will be admitted to hospital (~86,000 to 170,000 adults). Based on reported resistance rates, ~10% (~17,000) may be eligible for delafloxacin after failure of first-line antibiotics (~30 per 100,000 people).
Community-acquired pneumonia
Intravenous and
Oral

Trial or other data

Jan 21In the PIII DEFINE-CABP trial, i.v. then oral delafloxacin 300mg given twice daily was as effective as i.v. then oral moxifloxacin once daily or linezolid (twice daily). Early clinical response (in all patients who were clinically evaluable) occurred in 91% of patients in both groups. Complete cure and treatment success rates were similar. [10]
Oct 18In the PIII trial comparing delafloxacin with moxifloxacin in CAP, IV-to-oral delafloxacin met the primary endpoint of statistical non-inferiority (12.5% non-inferiority margin) for the Early Clinical Response at 96 hours (± 24 hours) after initiation of therapy (88.9% ECR in delafloxacin patients) compared to IV/oral moxifloxacin (89.0%) [4].
Mar 17PIII (NCT02679573; ML-3341-306) is currently recruiting patients in various countries including the US and some EU countries. Collection of primary outcome data is expected to complete Oct 18 [3].
Jan 16Melinta Therapeutics initiates a PIII study comparing delafloxacin with moxifloxacin for treatment of hospitalised patients with radiographic evidence of community-acquired bacterial pneumonia (CABP) (ML-3341-306). The study will assess clinical response 96 hours after the first dose, in approximately 860 patients randomised 1:1 to receive either delafoxacin or moxifloxacin [2].