dm+d

Unassigned

New Medicines

Primary cold agglutinin disease

Information

New molecular entity
Sanofi
Sanofi

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Pre-registration (Filed)
Yes
Yes
Sep 21According to Sanofi pipeline, sutimlimab is now pre-registration (as of Jun 21); presume US as not listed in EMA latest filings [14].
Jun 21Sutimlimab was prioritised for a NICE TA in Dec 2018 but it has not yet been added to the NICE work programme suggesting the company may not intend to market this in the UK [13].
Jun 21Sanofi plan a resubmission to FDA in the second half of 2021 and is also set up to file in EU [12].
Nov 20Sanofi notes that satisfactory resolution of the observations by the third-party manufacturer is required before the BLA can be approved and it remains in close contact with the FDA and the third-party manufacturer to reach a resolution in a timely manner [10].
Nov 20FDA reject sutimlimab due to deficiencies from a pre-license inspection of a third-party manufacturing facility. In its CRL, the FDA said there were no clinical or safety deficiencies with respect to the application but it cannot be approved until there are “satisfactory resolutions of the observations by the third-party manufacturer.” [9]
May 20US FDA has granted priority review of Biologics License Application (BLA) for sutimlimab for treatment of hemolysis in adult patients with cold agglutinin disease [8].
Oct 18Has breakthrough therapy status in US [4].
Oct 18Has orphan drug status in EU & US [4].
Jul 18Filings planned for 2020 [2].

Category

First-in-class, humanised monoclonal antibody that selectively inhibits an upstream serine protease within the C1-complex in the complement pathway, so preventing downstream signalling cascades, which results in phagocytosis, inflammation and cell lysis.
Cold agglutinin disease is a type of autoimmune hemolytic anemia defined by the presence of cold autoantibodies (autoantibodies which are active at temperatures below 30°C). It represents an estimated 16-32% of AIHA, whose annual incidence is estimated to be between 1/35,000-1/80,000 in North America and Western Europe [1].
Primary cold agglutinin disease
Intravenous infusion

Trial or other data

Jun 21A second phase 3 clinical trial (n=42) of Sanofi’s sutimlimab in people with cold agglutinin disease has met its primary endpoint. Sixteen of the 22 patients on sutimlimab had a 1.5-g/dL or more improvement in hemoglobin and were free from transfusions and the need for other non-permitted therapies after Week 5. The three measures made up the composite primary endpoint. One patient had a TESAE deemed by the investigator to be related to sutimlimab, namely a case of cerebral venous thrombosis in a person with a history of diabetes. The TESAEs headache, hypertension, rhinitis, Raynaud’s phenomenon and acrocyanosis were more common in the sutimlimab group than in the placebo cohort [12].
Apr 21Results of PIII Cardinal Study (NCT03347396) reported inn NEJM [11].
Dec 19Data from the PIII pivot CARDINAL study presented, reporting the primary efficacy outcome measure was met. The responder rate for a composite of an increase in hemoglobin (Hb) of ≥2 g/dL from baseline or reaching a Hb level ≥12 g/dL at 26-weeks and absence of transfusions from Weeks 5 to 26. This was met by 54% (n=13) of pts, with 62.5% achieving a Hb of ≥ 12 g/dL or an increase of >2g/dL and 71% remaining transfusion-free after week 5. Mean total bilirubin achieved near normalidation after th 1st week of treatment and fatigue scores demonstrated a clinically meaningful improvement from baseline. Most pts (91%) experienced adverse events; 29% were serious but none of these were assessedas related to sutimlimab. No pt discontinued sutimlimab due to infection and there were no meningococcal infections. [7]
Nov 19According to Sanofi, the Cardinal trial met its primary endpoint. Of 24 patients eventually enrolled, two left the trial for reasons unrelated to the drug and the remaining 22 have enrolled on the one-year follow-up phase [6].
May 19Collection of primary outcome data due to complete in Jun 20 (Cardinal) and Aug 20 (Cadenza) [5].
Nov 18PIII Cadenza trial to assess the efficacy and safety of sutimlimab in patients with primary CAgD without a recent history of blood transfusion starts (NCT03347422). The double-blind, parallel, randomised trial will enrol 40 patients. Collection of primary outcome data (responders and AEs) is due to complete Dec 19 [3].
Sep 18PIII Cadenza and Cardinal studies are recruiting [3].
Nov 17PIII Cardinal trial to assess the efficacy and safety of sutimlimab in patients with primary cold agglutinin disease (CAgD) who have a recent history of blood transfusion starts (NCT03347396). The open, prospective trial is enrolling 20 patients at sites including in the US & EU (plus UK). Primary outcomes are percentage of participants with response at week 26 and those with an adverse effects. A participant who meets all of the following criteria will be considered a responder: who did not receive a blood transfusion from Week 5 through Week 26 (end of treatment) and did not receive treatment for cold agglutinin disease (CAD) beyond what is permitted per protocol. Additionally the participant´s hemoglobin (Hgb) level must meet either of the following criteria: Hgb level greater than or equal to (>=) 12 gram per deciliter (g/dL) at the treatment assessment endpoint, or Hgb increased >= 2 g/dL from baseline (defined as the last Hgb value before administration of the first dose of study drug) at treatment assessment endpoint. Collection of these data is due to complete Jun 19 [3].

Evidence based evaluations