Ravulizumab

Unassigned

New Medicines

Ultomiris · Paroxysmal nocturnal haemoglobinuria (PNH) in adults and children - first-line

Information

Ultomiris
New molecular entity
Alexion
Alexion

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Launched
Yes
Yes
Sep 19 · Ravulizumab was withdrawn from the Community Register of designated orphan medicinal products on 11 June 2019 on request of the sponsor [16].
Jul 19 · Alexion is awaiting a positive recommendation from NICE and agreed funding from NHS England before providing a price or launch date. They are working with the HTA body to ensure a timely appraisal [15].
Jul 19 · Alexion announced that the European Commission has approved ravulizumab for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) as below ref 12 [13].
Apr 19 · CHMP has adopted a positive opinion for ravulizumab for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) with haemolysis with clinical symptoms indicative of high disease activity and those treated with eculizumab for 6 months who are clinically stable [12].
Mar 19 · A new market research report identifies ravulizumab as one of seven new drugs it believes will hit sales of $1 billion or more, the so-called “blockbuster” mark, by 2023 [11].
Feb 19 · One month after launch of Ultomiris, Alexion announce 5% of US patients have switched from Soliris (eculizumab) and virtually 100% of new starts are with Ultomiris. The company aims for a 70% switch in 2 years and has similar ambitions for Europe, starting with Germany, where launch is anticipated mid 2019 [10].
Dec 18 · FDA has approved ravulizumab (ULTOMIRIS™) for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) [9].
Jun 18 · Filed in EU for treatment of patients with PNH. The application is supported by comprehensive data from two PIII trials in more than 440 patients (the largest population of patients with PNH ever studied in Phase 3), which included patients who had never received a complement inhibitor, and patients who were stable on Soliris® (eculizumab) and switched to ALXN1210 [8].
Mar 18 · The company announched plans for regulatory submissions of ALXN1210 in PNH in the US., EU and Japan in the 2nd half of 2018 [6].
Jul 17 · Will be filed in the EU via the centralised procedure [5].
Jan 17 · ALXN 1210 gains orphan drug status for paroxysmal nocturnal haemoglobinuris in the US; orphan designation in the EU was granted in June 2016. A PIII trial in the US has recently started and a PII trial (NCT02605993, EudraCT2015-002674-20) is in progress in several countries including the UK [1].

Category

Long-acting humanised monoclonal antibody C5 complement inhibitor
PNH is a very rare acquired bone marrow disorder characterised by intravascular haemolysis, with resultant anaemia; before effective treatments were available, median survival was 10 years from diagnosis and half of those affected died from complications. Spontaneous recovery may occur, but only in a minority of patients. [2] UK incidence is about 0.13/100,000/year and 15-year prevalence is likely to be around 1.59/100,000 [3].
Paroxysmal nocturnal haemoglobinuria (PNH) in adults and children - first-line
Intravenous

Further information

Yes
To be confirmed

Trial or other data

Apr 18 · Positive topline data from ALXN1210 PIII switch study. The study showed pts with PNH can be effectively and safely switched from Soliris® (eculizumab) every 2 weeks to ALXN1210 every 8 weeks. The study demonstrated non-inferiority of ALXN1210 vs. Soliris® in pts with PNH who were stable on Soliris® based on change in LDH levels. The study also demonstrated non-inferiority on four key secondary endpoints: the proportion of pts with breakthrough hemolysis, change from baseline in quality of life, the proportion of pts avoiding transfusion and the proportion of pts with stabilised Hb levels. No pts treated with ALXN1210 experienced breakthrough haemolysis vs. 5 pts treated with Soliris®. ALXN1210 was well tolerated with a safety profile consistent with that of Soliris®. No pt withdrew from the study due to adverse events and no anti-drug antibody was observed for ALXN1210; one was observed for Soliris®. There were no cases of meningococcal infection observed in either the ALXN1210 or Soliris® arms.[7]
Mar 18 · Postive topline data from PIII trial comparing ALXN 1210 to eculizumab in treatment-naïve PNH pts. The co-primary endpoints were avoidance of transfusions and normalisation of lactate dehydrogenase (LDH) levels (a direct marker of complemented-mediated hemolysis). ALXN1210 showed non-inferiority for all four key secondary endpoints.The safety profiles of the two drugs were reported to be basically the same [6].
Oct 16 · PIII trial is in progress (NCT02946463), currently in the US only: it is an open label randomised comparison of ALXN1201 every 8 weeks with eculizumab every 2 weeks; primary outcomes are normalisation of lactate dehydrogenase levels and transfusion avoidance, both over 26 weeks, estimated recruitment will be 214, and estimated primary completion Dec 2017 [4].

Evidence based evaluations

Ultomiris · Atypical haemolytic uraemic syndrome in adults and children - first-line

Information

Ultomiris
Licence extension / variation
Alexion
Alexion

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Pre-registration (Filed)
Yes
Yes

Category

Long-acting humanised monoclonal antibody C5 complement inhibitor
Atypical hemolytic-uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction. Prevalence is 1-9 per 1,000,000 people [1].
Atypical haemolytic uraemic syndrome in adults and children - first-line
Intravenous

Evidence based evaluations