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New Medicines

MultistemTreatment of ischaemic stroke in adults

Information

Multistem
New molecular entity
Athersys
Athersys

Development and Regulatory status

Phase II Clinical Trials
None
Phase III Clinical Trials
Mar 20After completing the MASTERS-2 and TREASURE trials, Athersys plans to use the accelerated pathways to approval in the US, Europe and Japan (results expected in 2021) [7].
Apr 19The MASTERS-2 study is considered acceptable to support licence applications by the FDA & EMA [2].
Oct 17Granted regenerative medicine advanced therapy (RMAT) designation by the US FDA for treatment of ischaemic stroke [2].
May 17Granted fast track status in US [2].

Category

Allogeneic stem cell therapy, made from human stem cells obtained from adult bone marrow or other non-embryonic tissue sources, and then significantly expanded in a controlled manner (e.g. from a single qualified donor to produce millions of doses)
There are more than 100,000 strokes in the UK each year. The rate of first-time strokes in people aged 45 and over is expected to increase by 59% in the next 20 years (to 2035). In the same period, it is estimated that the number of stroke survivors, aged 45 and over, living in the UK is expected to rise by 123% [1].
Treatment of ischaemic stroke in adults
Intravenous infusion

Trial or other data

Nov 20Results from the PII MASTERS-1 trial (NCT01436487), conducted at 33 international stroke centres across the US and UK (including at University of Glasgow - Western Infirmary and Southern General Hospital, St. Georges Healthcare NHS Trust, University College London Hospitals - Thames Stroke Research Network, Newcastle upon Tyne Hospitals NHS Foundation Trust, and University Hospital of North Staffordshire) showed patients receiving MultiStem earlier in the treatment window (24-36 hours post-stroke) exhibited more favourable recovery on the primary and key secondary endpoints than patients who received placebo or patients who received MultiStem later (e.g. Excellent Outcome, p = 0.03). In the MultiStem treatment group 12.9% patients achieved a good clinical outcome by day 7 vs. 5.2% of patients who received placebo. Similarly, improvement in NIHSS ≥ 75% was achieved by 10.2% of MultiStem-treated patients vs. 3.9% of patients who were treated with placebo. Mortality was lower among patients who received treatment with MultiStem (4 deaths) vs. placebo (9 deaths). At two days following dosing, the MultiStem treated group had a significantly lower level of circulating CD-3+ T-cells, suggesting a reduction in the inflammatory response post-stroke, consistent with the therapeutic hypothesis. MultiStem treatment demonstrated that 15.4% patients had an excellent outcome (mRS =1, NIHSS =1, and Barthel Index =95) at day 90 vs. placebo group patients (6.6%), with p = 0.10. High percentage of patients in treatment-arm showed an excellent outcome vs. placebo group (23.1% vs. 8.2%, p = 0.02) at one year. Higher percentage of patients demonstrated an excellent clinical outcome when treated with MultiStem within 36 hours of stroke vs. placebo at one year (29.0% vs. 8.2%; p < 0.01) [6].
Sep 20PII/III TREASURE trial, being conducted in Japan by collaborative partner, HEALIOS K.K., is also recruiting; collection of primary outcome data due to complete Mar 21 [5].
Feb 20PIII MASTERS-2 trial, being conducted by Athersys under an FDA Special Protocol Assessment, is recruiting; timescales unchanged [5].
Dec 19NCT03545607 - no UK trial sites [4]
Jul 18PIII MASTERS-2 (MultiStem Administration for Stroke Treatment and Enhanced Recovery Study-2) trial to evaluate efficacy of allogeneic stem cell therapy for the treatment of patients who have suffered an ischaemic stroke starts (NCT03545607). The trial will enrol 300 patients in the US. The primary endpoint is to evaluate disability using modified Rankin Scale (mRS) scores at three months, comparing the distribution, or the “shift,” between the MultiStem treatment and placebo groups; collection of these data is due to complete Dec 20 [3].
Nov 17PII/III TREASURE trial to evaluate the safety of allogeneic stem cell therapy in patients with acute ischaemic stroke starts (NCT02961504). The trial will enrol 220 patients in Japan, and will assess patient recovery through approximately 90 days following initial treatment. The primary efficacy outcomes are proportion of subjects achieving an excellent outcome at three months following treatment; Excellent outcome is defined as mRS score of ≤1 (scale, 0 to 6), NIHSS score of ≤1 (scale, 0 to 42), and BI score of ≥95 (scale, 0 to 100), and adverse events. Patients enrolled in the trial will be randomised with either single dose of MultiStem or placebo within 18-36 hours of stroke [3].
Oct 17Unlike most other cell types that may be isolated from the human body, MultiStem is manufactured from human stem cells obtained from adult bone marrow or other non-embryonic tissue sources, and then significantly expanded in a controlled manner. It can be stored in frozen form until required. Athersys believes that MultiStem represents a potential best-in-class stem cell therapy based on its ability to be used without tissue matching or immunosuppressive drugs, its capacity for large scale production, its consistent safety profile, and its ability to deliver therapeutic benefit via more than one mechanism of action [2].

MultistemAcute respiratory distress syndrome in adults

Information

Multistem
Licence extension / variation
Athersys
Athersys

Development and Regulatory status

Phase II Clinical Trials
None
Phase II Clinical Trials
Mar 20Athersys announces that allogeneic stem cell therapy was designated as a “Highly Relevant” therapeutic for treatment of acute respiratory distress syndrome due to COVID-19 infections by the Biomedical Advanced Research and Development Authority (BARDA) [3].
May 19US-FDA grants fast track designation for clinical program evaluating MultiStem® cell therapy for the treatment of ARDS [3].

Category

Allogeneic stem cell therapy, made from human stem cells obtained from adult bone marrow or other non-embryonic tissue sources, and then significantly expanded in a controlled manner (e.g. from a single qualified donor to produce millions of doses)
ARDS is a common and devastating condition which can affect all adult patients, e.g. medical, surgical and obstetric patients. It occurs when non-cardiogenic pulmonary oedema (secondary to acute damage to the alveoli) leads to acute respiratory failure. In the UK, in one prospective six-month study to determine the incidence and outcome of ARDS in a UK adult university hospital ICU, 344 patients were admitted during the study period, of which 43 (12.5%) were determined to have ARDS [1].
Acute respiratory distress syndrome in adults
Intravenous infusion

Trial or other data

May 20Healios continues to recruit to the PII ONE-BRIDGE study. Athersys has a collaboration with Healios to develop and commercialise MultiStem for the treatment of ischaemic stroke and ARDS in Japan on an exclusive basis; Athersys is responsible for the supply of clinical product to Healios. Collection of primary outcome data is due to complete Dec 20. In Jan 20, Athersys announced one-year follow-up results from the MUST-ARDS study, providing further confirmation of tolerability, lower mortality and a greater number of ventilator-free and ICU-free days in the MultiStem-treated patient vs. the placebo group. Based on the promising results, Athersys is planning for a registrational trial in this indication [4,5].
Jan 19PII ONE-BRIDGE study to evaluate the efficacy and safety of MultiStem® cell therapy, in patients with ARDS caused by pneumonitis starts (NCT03807804). The open-label, standard therapy controlled study is expected to enrol approximately 30 patients in Japan. Primary endpoint of the trial will be the number of ventilator-free days – the days in which the patient was not on a ventilator in the 28 days following the treatment [3].
Jan 19Positive efficacy and safety results from the PI/II MUST-ARDS trial released by Athersys [3].
Jan 16PI/II study to assess Multistem® cell therapy in patients with acute respiratory distress syndrome starts (MUST-ARDS; NCT02611609). The double-blind, open, parallel, prospective, randomised trial will enrolled 36 patients in the US and the UK. UK trial sites are Queen Elizabeth Hospital (Birmingham), Addenbrooke Hospital (Cambridge), University College London, St. Georges Hospital (London), Manchester Royal Infirmary, Wythenshawe Hospital (Manchester) and John Radcliffe Hospital (Oxford) [2].