dm+d

Unassigned

New Medicines

Septic shock (sepsis) due to severe bacterial infections, initially necrotising soft tissue infection (NSTI)

Information

New molecular entity
Atox Bio
Atox Bio

Development and Regulatory status

None
None
Pre-registration (Filed)
Yes
Yes
Jan 22Not yet filed in EU.[15-17]
Dec 20US FDA accepts NDA for reltecimod for the treatment of suspected organ dysfunction or failure in patients with necrotizing soft tissue infection [14]
Jul 20Atox has reviewed the topline results of this trial with the US FDA. Atox Bio believes that the CE population reflects the more clinically relevant and statistically appropriate patient population for evaluation of the treatment effect of reltecimod. It plans to submit a New Drug Application (NDA) to the FDA in Q3 2020 under the Accelerated Approval Pathway with resolution of organ dysfunction being the basis for this approval pathway. Plans for filing in other jurisdictions not described [13].
May 20Pipeline notes that ACCUTE trial is complete and filing is anticipated in H2 2020. [12]
Jan 20PIII trials complete. [10,11]
Jan 19Still in PIII trials and on company pipeline.[7,9]
Feb 18In PIII trials. [5,6]
Aug 14orphan drug status in EU for treatment of NSTI granted by EMA [1].
Sep 12FDA grants Fast Track designation for treatment of NSTI [1].
Oct 11Orphan drug status granted by FDA for treatment of necrotising soft tissue infections (NSTI) [1].

Category

Immunomodulator: a synthetic peptide inhibiting the CD28 antigen and modulating over-reaction in the inflammatory cascade
The incidence of NSTI is estimated at 25-29,000 cases/year in the US with mortality of 15-20%.[9]
Septic shock (sepsis) due to severe bacterial infections, initially necrotising soft tissue infection (NSTI)
Intravenous infusion

Trial or other data

Jul 20 Results of the PIII ACCUTE trial announced. In the modified intent to treat (mITT) population on the necrotising infection clinical composite endpoint (NICCE) primary endpoint, 48.6% of patients achieved clinical success on reltecimod vs. a 39.9% success rate in patients on placebo (p=0.14). In assessment of resolution of organ dysfunction (defined as day 14 mSOFA =1 in combination with a decline of at least 3 mSOFA points from baseline), reltecimod demonstrated a distinct advantage over placebo (65.1% success vs. 52.6%, p=0.041). In the clinically evaluable (CE) analysis, 52.6% of patients receiving reltecimod achieved clinical success on the NICCE primary endpoint vs. 40.3% on placebo (p=0.039). In the evaluation of resolution of organ dysfunction, reltecimod demonstrated a strong clinically meaningful effect over patients receiving standard of care alone, with 70.9% of patients on reltecimod achieving resolution of organ dysfunction by day 14 vs. 53.4% on placebo (p=0.005). Consistent with these findings, in this study in patients who survived to day 14, whether on reltecimod or placebo, those that had resolved organ dysfunction by day 14 had a 90-day mortality of 2.4% vs. 21.5% in patients who had persistent organ dysfunction at day 14 (p<0.001) in the CE analysis population. While not showing a difference in mortality at day 28 and although not powered to show significance for mortality generally, in those patients surviving to day 14, the day 14 to day 90 mortality was 5.9% on reltecimod vs. 11.5% on placebo (p=0.12) in the CE analysis population. In the mITT analysis, the day 14 to day 90 mortality was 6.5% on reltecimod vs. 11.2% on placebo (p=0.17) [13].
Jan 20PIII ACCUTE study complete. Atox Bio expects to present the results in H1 2020. [10,11]
Jan 19 PIII ACCUTE study (NCT02469857) ongoing after the independent Data Monitoring Committee recommended it continue - the estimated primary completion date is Sept 19.[7,8]
Feb 18PIII study (NCT02469857) ongoing with a primary completion date of December 2018.[5,6]
Feb 17The Independent Data Monitoring Committee for the ACCUTE trial recommends continuation of the trial based on successful completion of a pre-specified futility analysis based on the first 102 patients enrolled [2].
Sep 15PIII trial initiated in US to evaluate efficacy and safety in patients with NTIS (ACCUTE, NCT02469857) [1]. Participants will receive reltecimod 0.5 mg/kg or saline placebo within 6 hours of diagnosis once it is surgically confirmed; primary outcome is a composite of five indicators of organ function and local signs of infection (including survival at day 28) compared to placebo, estimated recruitment is 290, and estimated primary completion date Dec 2018 [4].
Nov 12Atox Bio reports positive top-line results from a proof-of-concept PIIa trial (NCT01417780) that assessed two dose levels in patients (n=40) scheduled for urgent surgical intervention [1].