dm+d

Unassigned

New Medicines

GiaprezaHypotension in adults with septic or other distributive shock

Information

Giapreza
New molecular entity
PAION
La Jolla

Development and Regulatory status

Licensed but not launched
Launched
Launched
Apr 22Company plans on continuing commercial launch of product in Europe including the UK for 2022. Launch expected by the end of 2022/early 2023 in selected European countries [15]
Jul 21Launched in Germany. PAION decided to make Giapreza available before establishing a commercial structure in Germany. Other European markets are to follow over the course of the next months in a staggered manner by country so that, by the end of 2022, launches will have been conducted in all selected European markets [14].
Jan 21La Jolla has out-licensed Giapreza in Europe to PAION AG. Launch is expected in Europe in late 2021 [13].
Mar 20La Jolla has agreed to supply Giapreza to an individual UK hospital using the UK Specials procedure in light of the COVID-19 pandemic. Other trusts wishing to obtain supplies are advised to contact La Jolla [12].
Sep 19La Jolla expects to launch in Europe in early 2020 [10].
Aug 19Approved in EU [9].
Jun 19Recommended for EU approval by CHMP - the full indication is "for the treatment of refractory hypotension in adults with septic or other distributive shock who remain hypotensive despite adequate volume restitution and application of catecholamines and other available vasopressor therapies (see section 5.1)”. It is proposed that the drug be prescribed by physicians experienced in the treatment of shock and used in an acute and hospital setting [8].
Jun 18According to the company, the EMA has accepted and validated the Marketing Authorisation Application for angiotensin II infusion. The indication being sought is treatment of hypotension in adults with distributive or vasodilatory shock who remain hypotensive despite fluid and vasopressor therapy, and the MAA is based on the results of the ATHOS-3 study (NCT02338843) [7].
Mar 18Launched in US [6].
Dec 17Approved in the US. Launch planned for March 2018. Analysts suggest use initially will be as a third-line treatment after noradrenaline and vasopressin have failed, but may also get some second-line use [5].
Aug 17The FDA has accepted the New Drug Application for angiotensin II (LJPC-510) in the treatment of hypotension in adults with distributive or vasodilatory shock who remain hypotensive despite fluid and vasopressor therapy, according to a company statement. The application has been given Priority Review status, with a target action date of 28th Feb 2018 [4].
Mar 15ATHOS-3 study (NCT02338843) is a PIII multi-national study recruiting in the US, EU (including UK) and elsewhere [2].

Category

Synthetic angiotensin II, a peptide agonist of angiotensin receptor, acts as a vasoconstrictor to help the kidneys balance body fluids and electrolytes by improving sodium excretion and urine output.
Distributive shock is the most common type of shock with about 90% of cases being septic shock. Septic shock has been reported to be associated with high risk of mortality despite treatment. There are at least 245,000 cases of sepsis in the UK every year. Approximately 6-7% of critically ill patients may develop refractory shock [16, 17]
Hypotension in adults with septic or other distributive shock
Intravenous infusion

Further information

Yes

Trial or other data

May 17La Jolla announces full data from a PIII trial. Although LJPC-501 met its primary outcome, there was no improvement in mortality and total organ function [3].
Feb 17La Jolla announces positive top-line data from its PIII trial. The primary endpoint of percentage of patients hitting targeted BP response was seen in 23% of the 158 placebo-treated patients vs. 70% of the 163 LJPC-501-treated patients (p < 0.00001). The primary endpoint was the percentage of patients with a mean arterial pressure (or MAP) of ≥ 75 mmHg or a 10-mmHg increase from baseline MAP at three hours following treatment and without an increase in standard-of-care vasopressors. Although not powered for survival, the company also noted a trend toward longer survival was observed: 22% reduction in mortality risk through day 28 for LJPC-501-treated patients (hazard ratio 0.78 (0.57-1.07); p = 0.12) [1].
Mar 15La Jolla initiates the PIII ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock) 3 trial to investigate the safety and efficacy of LJPC 501 in adults with CRH (LJ501-CRH01; NCT02338843). The primary efficacy endpoint of the trial is to compare the change in mean arterial pressure between the two groups in the trial. The randomised, double-blind, placebo-controlled trial will enrol approximately 315 patients. Enrolment has begun in the US, Canada, Finland, Australia and New Zealand. This trial forms the part of a registration program, which initiated as a result of an agreement between the FDA and the company on Special Protocol Assessment to utilise blood pressure as the primary endpoint for the approval of LJPC 501 in CRH [1].

Evidence based evaluations