dm+d

Unassigned

Refrigerated Storage

XeravaPaion

Paion
Xerava
Powder for concentrate for solution for infusion

In the event of an inadvertent temperature excursion the following data may be used:

The product is stable when exposed to a temperature excursion of 25ºC for 6 months.

Contact Paion in cases where additional stability data is required. Refer to the electronic medicines compendium (eMC) at https://www.medicines.org.uk for company contact details.

10 March 2022
London MI Service

New Medicines

Xerava Complicated intra-abdominal infections in adults - first-line

Information

Xerava
New molecular entity
PAION
Tetraphase

Development and Regulatory status

Launched
Launched
Launched
April 2022
Apr 22Xerava available in the UK. Price for 100mg vial, 1=£105.00; 10=£1050.00 [26]
Feb 22Expected to launch in UK April 22. [25]
Sep 21Launched in the Netherlands. PAION is currently launching all of its products - Byfavo, GIAPREZA and XERAVA - in a staggered manner by country so that by the end of 2022, launches are planned to have been conducted in most key European markets [24].
May 21Company have intention to market in UK. [22]
Jan 21Paion enter into a license agreement with La Jolla Pharmaceutical Company for XERAVA(TM) (eravacycline) for the commercialisation of products in the European Economic Area, the United Kingdom and Switzerland (the Territories). [23]
Nov 18Tetraphase plans to commercialise Xerava in certain European countries, but also through collaboration arrangements. No details provided of UK plans [21].
Oct 18The wholesale acquisition cost of Xerava in the US is $175 per day of therapy to support use for the empiric treatment of cIAI [20].
Oct 18Launched in US [19].
Sep 18Approved in the EU [18].
Aug 18Approved by the FDA [17].
Jul 18CHMP issues positive opinion, recommending the granting of a marketing authorisation for the medicinal product Xerava, for the treatment of complicated intra-abdominal infections in adults [16].
Jan 18Filed in US for treatment of complicated abdominal infections. Submission is based on the IGNITE1 and IGNITE 4 PIII trials [15].
Aug 17Filed in EU for the treatment of complicated intra-abdominal infections (cIAI) via centralised procedure [14].
Jul 17Tetraphase plans to submit a NDA, which will be supported by data from IGNITE1 and IGNITE4, to the FDA in Q1 2018. They are on track to submit a MAA to the EMA during Q3 2017 [13].
May 16The FDA requests an additional PIII trial before it will support an NDA submission. Tetraphase will in fact do two new studies: the first, for twice-daily IV eravacycline in patients with complicated intra-abdominal infections (cIAI). The study is set to take place early in Q4 2016 with top-line results available in Q4 2017. The second PIII trial will be for once-daily IV eravacycline in patients with complicated urinary tract infections (cUTI). This will go toward a supplementary NDA for an additional indication of cUTI [10].
Jan 16Still listed in PIII development on company website [9].
Apr 14US FDA has granted Fast Track designations for both the intravenous (IV) and oral formulations of eravacycline [5].
Mar 1450% of targeted enrollment has been achieved in the PIII IGNITE 1 study (NCT01844856). Top-line data is expected in Q1 2015. The company plans to file in the US by end of 2015 [4].
Jul 13The FDA has designated eravacycline a Qualified Infectious Disease Product (QIDP) for complicated intra-abdominal infection (cIAI) and urinary tract infection (cUTI) indications. The company will be eligible to benefit from certain incentives for the development of new antibiotics including priority review and fast-track status [2].

Category

Fully synthetic tetracycline antibiotic
Complicated intra-abdominal infections (IAIs) are associated with very high mortality rates, particularly among critically ill patients. IAIs may be community- or hospital-acquired and treatment options are limited due to resistance to commonly used antibiotics.
Complicated intra-abdominal infections in adults - first-line
Intravenous infusion

Trial or other data

Jul 17Tetraphase announce positive top-line results from PIII IGNITE4 trial (n=500). Eravacycline met primary endpoint of statistical non-inferiority of clinical response at test-of-cure visit, under guidance set by FDA and EMA (12.5% non-inferiority margin) [13].
Sep 16Enrolment of approximately 400 patients to PIII IGNITE 4 (NCT02784704) has begun. Trial will assess efficacy, safety and pharmacokinetics of twice-daily IV eravacycline compared with meropenem. Primary endpoint is clinical response at the test-of-cure (TOC) visit, which occurs 25 to 31 days after the initial dose of the study drug. Top-line results are expected in fourth quarter of 2017 [12].
Jul 16 A further PIII study, IGNITE 4 is currently recruiting and will compare eravacycline with meropenem - it is due to complete in December 2017 [11].
Apr 15Eravacycline met primary endpoints in PIII IGNITE1 study in 541 pts with complicated intra-abdominal infection (cIAI). Detailed results presented at the 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). IGNITE1, a randomised, multi-centre, double-blind, double-dummy global PIII trial, assessed the efficacy and safety of intravenous eravacycline 1.0 mg/kg every 12 hours vs. intravenous ertapenem 1 g every 24 hours, in the treatment of cIAI. The primary endpoint was clinical response at the test-of-cure (TOC) and 86.8% and 87.6% of pts receiving eravacycline and ertapenem achieved a clinical cure respectively. The most common Gram-negative pathogens in the study included Escherichia coli, Klebsiella pneumonia and Pseudomonas. Eravacycline achieved high cure rates against these pathogens, as well as in pts with Acinetobacter baumannii and in pts with suspected ESBL-producing pathogen isolates. There were no drug-related serious adverse events in the trial. The most common drug-related adverse events for eravacycline were gastrointestinal, including nausea (3.3%, n=9) and emesis (2.2%, n=6) [8].
Dec 14Tetraphase reported positive top-line results from the PIII IGNITE 1 trial of eravacycline for the treatment of complicated intra-abdominal infection (cIAI) compared to ertapenem. In the trial, eravacycline met the primary endpoint of statistical non-inferiority of clinical response at the test-of-cure (TOC) visit, under the guidance set by the FDA and the EMA [7].
Jul 14Patient enrollment in Phase 3 IGNITE 1 [NCT01844856] completed. Top-line results from IGNITE 1 expected in early first quarter 2015 [6].
Sep 13NCT01844856 - The first patient is dosed [3].
May 13NCT01844856 (TP-434-008) is a PIII, randomized, double-blind, double-dummy, multicentre study of eravacycline (IV infusion 1mg/kg 12 hourly) vs ertapenem in 536 patients with complicated intra-abdominal infections. The primary outcome is clinical response at the test-of-cure (TOC) visit (25-31 days after first dose) in the microbiological ITT population. The study starts Aug 13 and is due to complete Jan 15 [1].

Evidence based evaluations