dm+d

38194311000001107

Refrigerated Storage

UltomirisAlexion Pharma UK Ltd

Alexion Pharma UK Ltd
Ultomiris
Concentrate for solution for infusion (300mg/3mL , 1100mg/11mL)

Contact Alexion Pharma UK Ltd in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

11 November 2021
London MI Service

New Medicines

UltomirisParoxysmal nocturnal haemoglobinuria (PNH) in adults - first-line

Information

Ultomiris
New molecular entity
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

Launched
Launched
Launched
February 2021
Yes
Oct 21Has been available in Europe since 2019. In Germany, 45% of PNH patients on Soliris had switched to Ultomiris as of Oct 19 —around three months ahead of the time Ultomiris took to hit the same milestone in the US [18].
Feb 21Available in UK. 100mg/ml conc for soln for inf in vial, 3ml=£4,533.00; 11ml=£16,621.00. Also 10mg/ml conc, 30ml= £4,533.00 [17].
Sep 19Ravulizumab was withdrawn from the Community Register of designated orphan medicinal products on 11 June 2019 on request of the sponsor [16].
Jul 19Alexion 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 19Alexion 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 19CHMP 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 19A 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 19One 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 18FDA has approved ravulizumab (ULTOMIRIS™) for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) [9].
Jun 18Filed 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 18The company announched plans for regulatory submissions of ALXN1210 in PNH in the US., EU and Japan in the 2nd half of 2018 [6].
Jul 17Will be filed in the EU via the centralised procedure [5].
Jan 17ALXN 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 - first-line
Intravenous

Further information

Yes

Trial or other data

Apr 18Positive 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 18Postive 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 16PIII 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

UltomirisAtypical haemolytic uraemic syndrome in adults and children ≥10kg

Information

Ultomiris
Licence extension / variation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

Launched
Launched
Launched
March 2021
Yes
Yes
Oct 21Has been available in Germany since approval in Jun 20 [11].
Feb 21Available in UK. 100mg/ml conc for soln for inf in vial, 3ml=£4,533.00; 11ml=£16,621.00 [10].
Jun 20Approved in EU for treatment of adults and children with a body weight of 10 kg or above with aHUS who are complement inhibitor treatment-naïve or have received eculizumab for at least three months and have evidence of response to eculizumab [9].
Apr 20Recommended for EU approval by CHMP - the additional indication is "in the treatment of patients with a body weight of 10 kg or above with atypical haemolytic uremic syndrome (aHUS) who are complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab" [8].
Oct 19FDA approved including for treatmend of patients one month of age and older [7].
Jul 19Also pre-registration in EU [6].
Jun 19Filed in the US where it has been granted priority review status. Target action date set at 19 October 2019 [5].
May 18Will be filed in EU using centralised procedure [3].

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 ≥10kg
Intravenous

Further information

Yes

Trial or other data

Jan 19PIII ULTOMIRIS aHUS-311 study (NCT02949128)meets primary endpoint. This global, multicentre, single arm study evaluated the safety and efficacy of i.v. ULTOMIRIS administered in 56 adults (≥ 18) who hadn’t been treated with a complement inhibitor before. Pts received a weight-based loading dose (≥ 40 to < 60 kg = 2,400 mg; ≥ 60 to < 100 kg = 2,700 mg; ≥ 100 kg = 3,000 mg) on day 1, followed by weight-based maintenance doses (≥ 40 to < 60 kg = 3,000 mg; ≥ 60 to < 100 kg = 3,300 mg; ≥ 100 kg = 3,600 mg) on day 15 and then once every 8 weeks. Complete TMA response (= primary endpoint, defined as normalisation of platelet count AND lactate dehydrogenase (LDH) level AND an improvement in serum creatinine of ≥ 25%) over 26-weeks was acheived by 53.6% (95% CI [39.6% to 67.5%]) of pts which was sustained over the 8-week dosing interval. Treatment with ULTOMIRIS resulted in reduced thrombocytopenia, haemolysis and improved kidney function. The safety profile was consistent with that observed in two PIII studies in pts with paroxysmal nocturnal hemoglobinuria (PNH) [4].
Apr 18Both PIII studies are still recruiting [2].
Jul 17PIII study to evaluate ALXN1210 in 16 children and adolescent patients with aHUS naïve of treatment with complement inhibitor starts (NCT03131219). Recruitment is taking places in several countries including US & EU. Primary outcome is complete TMA response; collection of these data is due to complete Dec 18 [2].
Nov 16PIII study to evaluate ALXN1210 in 55 adult and adolescent patients with aHUS naïve of treatment with complement inhibitor starts (NCT02949128). Recruitment is taking places in several countries including US & EU (inc. UK). Primary outcome is complete TMA response; collection of these data is due to complete Nov 18 [2].

Evidence based evaluations

UltomirisParoxysmal nocturnal haemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) - 100mg/ml (advanced) IV formulation

Information

Ultomiris
New formulation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

Launched
Approved (Licensed)
Launched
March 2021
Yes
Yes
Jul 21Ultomiris 1100mg in 11ml vials (price £16,621/vial) and 300mg in 3ml vials (price £4,533/vial) are available in the UK, possibly since March 2021 [8].
Nov 20EMA approves a new strength (1100mg in 11ml vial, concentration 100mg/ml) for Ultomiris concentrate for solution for infusion, and a new presentation (300mg in 3ml vial, concentration 100mg/ml) including changes in the active substance concentration, and excipients composition and concentrations [7].
Oct 20Launched in US. A decision is expected in EU in November [6].
Oct 20FDA has approved ravulizumab 100 mg/mL formulation for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) and for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy for adult and pediatric (one month of age and older [5].
Sep 20UK launch plans for this formulation are unknown, but is likely to be affected by NICE decisions on approval for use in aHUS and PNH, which are still pending. The TA for aHUS has now been rescheduled into the work programme and is due to be discussed at committee on 13 April 2021; the TA for PNH is due to be discussed earlier at committee on 10 March 2021 [4].
Sep 20The CHMP has recommended marketing authorization in the EU for a new 100 mg/mL intravenous (IV) advanced formulation of Ultomiris. Ultomiris is administered every eight weeks for the treatment of PNH and aHUS. Ultomiris 100 mg/mL would constitute an advancement in the treatment experience for patients with aHUS and PNH by reducing average annual infusion times by approximately 60% compared to Ultomiris 10 mg/mL while delivering comparable safety and efficacy. With Ultomiris 100 mg/mL, most patients will spend six hours or less a year receiving treatment. The European Commission decision is anticipated in Nov 20 [3].
Sep 20Positive opinion from CHMP [1].

Category

Long-acting C5 complement inhibitor.
PNH is a rare disease where haemolytic anaemia occurs due to the action of complement on erythocyte call membranes. aHUS or atypical hemolytic uremic syndrome (also rare) involves complement-mediated thrombotic microangiopathy resulting in haemolysis [2].
Paroxysmal nocturnal haemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) - 100mg/ml (advanced) IV formulation
Intravenous

UltomirisParoxysmal nocturnal haemoglobinuria (PNH) in children and adolescents

Information

Ultomiris
Licence extension / variation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

Launched
Launched
Launched
October 2021
Yes
Oct 21MHRA approves ravulizumab to treat PNH in children and adolescents. The amended indication is treatment of adult and paediatric patients with a body weight of 10kg or above with with PNH, in patients with haemolysis with clinical symptom(s) indicative of high disease activity and in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months [11].
Sep 21Ravulizumab has been approved in the European Union for expanded use to include children (with a body weight of 10 kg or above) and adolescents with paroxysmal nocturnal haemoglobinuria (PNH) [9]
Jul 21EU CHMP issues a positive opinion recommending an extension to an existing indication to include use in paediatric patients. The proposed new indication is treatment of adult and paediatric patients with a body weight of 10kg or above with paroxysmal nocturnal haemoglobinuria, in patients with haemolysis with clinical symptom(s) indicative of high disease activity. and in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months [8].
Jun 21The FDA has approved the expanded use of ravulizumab-cwvz to include children (one month of age and older) and adolescents with paroxysmal nocturnal hemoglobinuria [7].
Mar 20Has orphan drug status in US [4].
Jun 19Ravulizumab for PNH was withdrawn from the EU Community Register of designated orphan medicinal products on request of the sponsor [5].

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 children and adolescents
Intravenous

Trial or other data

Jun 21Data from PIII trial (NCT03406507) presented at 26th Congress of the European Haematology Association (EHA-2021). Ravulizumab was found to be effective and provided immediate, complete, and sustained terminal complement inhibition irrespective of prior treatment with eculizumab. Out of 13 patients enrolled, 10 (83.3%) patients were aged ≥ 12 years, with a median (range) age at first ravulizumab infusion of 15.0 (9–17) years. Complete terminal complement inhibition was attained by the end of first ravulizumab infusion (defined as mean serum free C5 concentration < 0.5 μg/mL) and was sustained through Day 183 in all patients. Mean (SD) percentage change in LDH was –42.1% (59.0) in complement-inhibitor-naïve patients and remained stable in eculizumab-experienced patients at +4.65% (44.7). Overall, 10 (83.3%) patients achieved transfusion avoidance (TA), 8 (66.7%) achieved Hgb-S and no patients experienced breakthrough haemolysis (BTH). Steady-state therapeutic serum concentrations of ravulizumab were achieved immediately following the first dose and maintained throughout the primary evaluation period with no evidence of accumulation (mean [SD] Cmax and Ctrough accumulation ratios of 1.1 [0.1] and 1.1 [0.2], respectively) [10].
Jul 20PIII trial estimated primary completion now June 2021 [6].
Oct 19PIII study (NCT03406507) is recruiting [1].
Feb 18PIII trial to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ALXN1210 in paediatric patients with paroxysmal nocturnal haemoglobinuria (PNH) starts (NCT03406507). The open-label trial will enrol 12 patients up to 18 years of age in the UK, the US, the Netherlands, Norway, Russian Federation and France. Collection of primary outcome is due to complete Aug 20 [1].

Evidence based evaluations

UltomirisNeuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4-seropositive

Information

Ultomiris
Licence extension / variation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

First in class, humanised monoclonal antibody C5 complement inhibitor
Neuromyelitis Optica is a rare disorder affecting eyes and spinal cord leading loss of vision, mobility, and sensation. 90% of patients have relapsing NMO. It affects about 0.4 in 10,000 people in the EU equivalent to a total of around 20,000 people.
Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4-seropositive
Intravenous

Evidence based evaluations

UltomirisGeneralised myasthenia gravis in adults

Information

Ultomiris
Licence extension / variation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

None
Recommended for approval (Positive opinion)
Launched
Jul 22Recommended for EU approval by CHMP – the extension to the existing indication is for use “as an add-on to standard therapy for the treatment of adult patients with gMG who are anti-acetylcholine receptor (AChR) antibody-positive” [10].
Apr 22FDA approves ravulizumab to treat gMG [8].
Dec 21Supplemental Biologics License Application (sBLA) has been accepted for Priority Review by the US Food and Drug Administration (FDA) with a Prescription Drug User Fee Act date during the second quarter of 2022, following use of a rare disease priority review voucher by Alexion, AstraZeneca’s Rare Disease group [6]
Dec 21Is currently pre-registration in EU. Has been filed using the centralised procedure [5].

Category

First in class, humanised monoclonal antibody C5 complement inhibitor
The incidence ranges from 0.3 to 2.8 per 100,000. It is estimated to affect more than 700,000 people worldwide. The prevalence of MG in the UK is estimated at about 15 per 100,000 population. Peak incidence is in the third decade for women and the sixth or seventh decade in men [1].
Generalised myasthenia gravis in adults
Intravenous

Further information

Yes

Trial or other data

Apr 22Results of PIII Champion-MG trial (NCT03920293) are published in NEJM [9].
Apr 22AstraZeneca presents follow-up results from the PIII Champion-MG trial (NCT03920293) at the American Academy of Neurology (AAN) annual meeting. The open-label extension of the study shows long-term efficacy in those with anti-acetylcholine receptor (AChR) antibody-positive gMG, with improvements in daily activities, muscle strength and quality of life which sustained for more than a year [7].
Jul 21Alexion announces positive topline results from PIII study. Study met primary endpoint of change in baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at week 26´ and in patient who completed extension study the positive treatment effect was maintained through a total of 52 weeks [4]
Feb 21Results from PIII NCT03920293 are expected in H2 2021 [3].
Feb 20PIII study (NCT03920293) is recruiting [1].
Mar 19PIII study to evaluate the safety and efficacy of intravenous ravulizumab, in patients with generalized myasthenia gravis starts (NCT03920293). 160 adults will be enrolled in the US. Primary outcome is change from Baseline In Myasthenia Gravis-Activities Of Daily Living (MG-ADL) Total Score At Week 26; collection of these data is due to complete Dec 21 [1].

Evidence based evaluations

Ultomiris Atypical haemolytic uraemic syndrome and paroxysmal nocturnal haemoglobinuria - SC formulation

Information

Ultomiris
New formulation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

None
Phase III Clinical Trials
Pre-registration (Filed)
Feb 22Has been filed in the US [9].
Oct 21The PIII study of weekly subcutaneous ULTOMIRIS demonstrated PK-based non-inferiority versus intravenous ULTOMIRIS. Pending collection of 12-month safety and drug-device combination data, Alexion plans to file for approval in the US for the ULTOMIRIS SC formulation and device combination in PNH and aHUS in Q3 21, and in the EU in Q1 22 [7].
Apr 20Following a portfolio prioritization, Alexion has made the decision to not proceed with further development of ALXN1810, subcutaneous ULTOMIRIS co-administered with ENHANZE technology [6].
Dec 17Alexion (now Alexion AstraZeneca Rare Disease) and Halozyme Therapeutics enter into a collaboration and license agreement that provides Alexion access to Halozyme ENHANZE drug-delivery technology for the development of subcutaneous formulations for their portfolio of products. Alexion can use the technology for exclusive development of up to four targets including ravulizumab (ALXN 1210 SC), to potentially further extend the dosing interval of ALXN 1210 SC to once every two weeks or once per month. The ENHANZE ravulizumab product will be known as ALXN 1810 [4].

Category

Long-acting humanised monoclonal antibody C5 complement inhibitor in a drug-device combination, administered by once-weekly infusion.
Atypical hemolytic uremic syndrome (aHUS) is an extremely rare disease characterised by hemolytic anemia, thrombocytopenia and uremia. In Europe, the disorder affects ~0.11 per 1 million individuals aged 0-18 years. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder that affects between 0.5-1.5 per million people in the general population [3].
Atypical haemolytic uraemic syndrome and paroxysmal nocturnal haemoglobinuria - SC formulation
Subcutaneous infusion

Trial or other data

Jun 20The ongoing global PIII open-label, parallel-group study evaluating ULTOMIRIS SC compared with ULTOMIRIS IV (EudraCT2017-002370-39; NCT03748823; ALXN1210-PNH-303) enrolled 136 adults with PNH who are clinically stable and have previously been treated with eculizumab for at least three months prior to study entry. It recruited in Germany, France, Belgium, the UK, the Netherlands, Sweden, Finland, Czech Republic, Spain and Argentina. The primary objective is ULTOMIRIS serum trough concentration at Day 71. The study remains ongoing to assess secondary endpoints, including safety, immunogenicity and various PK/PD, quality of life, device performance and efficacy measures. Patients were stratified by weight groups (≥40 to <60kg and ≥60 to <100kg) and then randomized 2:1 to receive either ULTOMIRIS SC or ULTOMIRIS IV. All patients received an initial IV loading dose on Day 1. On Day 15, patients in the ULTOMIRIS SC group began receiving a once-weekly self-administered fixed-dose of ULTOMIRIS SC, and patients in the ULTOMIRIS IV group received a single infusion of the approved weight-based IV dose. The study met its primary objective, with ULTOMIRIS SC demonstrating PK-based non-inferiority versus ULTOMIRIS IV at Day 71 (p < 0.0001 for non-inferiority in serum ULTOMIRIS trough concentration - C[trough]). Serum free C5 concentrations were maintained below the target threshold in all patients, and mean lactate dehydrogenase levels remained stable below the upper limit of normal. Preliminary safety data through the 71-day randomized treatment period of the study were consistent with the known safety profile of ULTOMIRIS and did not result in any unexpected safety findings. No adverse events led to withdrawal of study drug in either arm. No serious adverse device effects or meningococcal cases were reported, and no anti-drug antibodies were observed. Of the 135 patients who completed the RCT treatment portion of the study, all but one participant chose to continue in the ongoing SC-only extension period, where all patients are receiving weekly ULTOMIRIS SC for up to an additional 182 weeks. The extension period will provide 12 months of safety data required for regulatory submissions to applicable health authorities, now anticipated in the third quarter of 2021 to accommodate all regulatory requirements for this combination device filing [8].
Jun 20Alexion announces PIII study of weekly SC ravulizumab met primary endpoint of phamacokinetic-based non-inferiority vs ravulizumab IV at Day 71 [2].
Jul 19Alexion initiate a PIII trial to compare pharmacokinetics of ravulizumab subcutaneous (SC) administered via an on-body delivery system (OBDS) to ravulizumab intravenous (IV) in patients with paroxysmal nocturnal hemoglobinuria (PNH) currently treated With eculizumab (EudraCT2017-002370-39) [1].

Information

Ultomiris
Licence extension / variation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Long-acting humanised monoclonal antibody C5 complement inhibitor. Weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 4 to 8 weeks.
An uncommon but devastating consequence of HSCT is transplantation-associated thrombotic microangiopathy (TA-TMA). The incidence of TA-TMA ranges from 0.5% to 76%, with a mortality rate of 60-90% despite treatment [1].
Haematopoietic stem cell transplant-related thrombotic microangiopathy (HCST-TMA)
Intravenous infusion

Ultomiris Complement-mediated thrombotic microangiopathy (CM-TMA)

Information

Ultomiris
Licence extension / variation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Long-acting humanised monoclonal antibody C5 complement inhibitor.
CM-TMA is a group of rare, potentially life-threatening syndromes (both hereditary and acquired) that reflect tissue responses to severe endothelial damage. It is caused by a number of different disorders including atypical haemolytic uraemic syndrome (aHUS). 90% of cases are due to secondary aHUS (including HSCT-TMA, cancer, pregnancy, hypertensive emergency). Prevalence of specific TMA syndromes is challenging to define in adults; relative frequency of the different syndromes is unknown [1,2].
Complement-mediated thrombotic microangiopathy (CM-TMA)
Intravenous infusion

Ultomiris Amyotrophic lateral sclerosis (motor neurone disease) in adults

Information

Ultomiris
Licence extension / variation
Alexion AstraZeneca Rare Disease
Alexion AstraZeneca Rare Disease

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Aug 21Development for ALS discontinued [3].

Category

Long-acting humanised monoclonal antibody C5 complement inhibitor
MND is relatively uncommon with an annual incidence of about 2 cases per 100,000 population. Prevalence is about 5-7 per 100,000. General practitioners can expect to see one or two cases in their career. It can occur at any age but is more common in people aged over 50. The male to female ratio is 2:1 [1].
Amyotrophic lateral sclerosis (motor neurone disease) in adults
Intravenous infusion

Trial or other data

Aug 21Following a review of data from PIII CHAMPION-ALS RCT, the Independent Data Monitoring Committee recommend trial be discontinued due to lack of efficacy. No new safety findings were observed, and data were consistent with the safety profile of ravulizumab [3].