dm+d

Unassigned

New Medicines

Treatment of muscle injury following arthroplasty for hip fracture

Information

New molecular entity
Pluristem Therapeutics
Pluristem Therapeutics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Dec 20Data readout from PIII trial expected Q3 21 [5].
Apr 20Company pipeline shows PXL-PAD is PIII for hip fracture. Pluristem believes that cell therapies could significantly improve post-surgical outcomes for these patients by improving muscle regeneration [2].

Category

Allogeneic ex-vivo expanded placental mesenchymal-like adherent stromal cells that stimulate the body to heal. An ‘off-the-shelf’ tissue-engineered ATMP, needing no genetic or tissue matching.
Around 76,000 hip fractures occur each year in the UK as a whole. Half of people with hip fractures sustain displaced intracapsular fractures, and since most are not ideally suited for total hip arthroplasty (>90%), hemiarthroplasty remains the commonest operation recorded by the NHFD. Rates of successful mobilisation varied considerably between units; figures for units in England ranged from 36-100% [1].
Treatment of muscle injury following arthroplasty for hip fracture
Intramuscular

Trial or other data

Jul 20PIII (NCT03451916) study is recruiting; collection of primary outcome data now expected to finish in Jun 21 [4].
Apr 19PIII (NCT03451916) study is recruiting [3].
Jul 18Pivotal PIII trial to evaluate safety, efficacy and tolerability of emiplacel in the patients with muscle injury following hip replacement or reconstruction due to hip fracture starts (NCT03451916; PLX-HF-01). 240 adultsa ged 60 to 90 years will be recruited in Denmark, Germany, US and Israel and the UK (sites are Norfolk and Norwich University Hospital plus John Radcliffe Hospital in Oxford). Primary outcome is Short Physical Performance Battery (SPPB) score at week 26; collection of these data is due to complete Jul 20 [3].

Evidence based evaluations

Critical limb ischaemia with minor tissue loss for patients with peripheral arterial disease or muscle injuries who are unsuitable for revascularisation

Information

New molecular entity
Pluristem Therapeutics
Pluristem Therapeutics

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Dec 20Pleuristem are discontinuing development of emiplacel following a review by the independent Data Monitoring Committee (DMC). The DMC concluded that the therapy was unlikely to meet its primary endpoints in the CLI study population [18].
Dec 20Data readout from an interim analysis of the PIII PACE study expected before year end [17].
Apr 20Pluristem reports that enrolment in the PIII study is advancing with more than 80% patients enrolled, but has slowed in April, 2020. Pluristem is now finalising discussions with the FDA and EMA regarding the interim data readout, confirming understandings on endpoint, timing, and procedures for cleaning data during COVID-19 limitations. It expects an announcement of the interim readout top line results to be delayed to the beginning of Q4 2020 [14].
Apr 20Has fast track status in US for CLI [13].
Apr 20Pluristem announces it is holding discussions with the FDA and EMA in order to confirm and agree on changes in trial parameters and final protocol design, which may lead to conditional marketing approval in Europe. It expects to be able to update on those understandings in the coming weeks [12].
Nov 19Company announces intention to file with the EMA [11].
Nov 18US FDA expanded the early access programme (EAP) for emiplacel, making the stem cell therapy available to patients with CLI who are unsuitable for revascularisation and cannot take part in ongoing PACE trial [9]
Feb 17Pluristem announces it has made significant strides towards marketing approval of PLX-PAD in the treatment of critical limb ischemia (CLI). Study initiation of the pivotal PIII trial in CLI received clearance from regulatory authorities in the US, UK and Germany. Based on these clearances, the Company expects to begin enrolling patients in this study in H1 2017. An interim analysis of data collected on the first half of recruited patients is planned, potentially leading to early conditional marketing approval in Europe via the EMA adaptive pathway pilot project. Full enrolment is to be completed as planned to pursue full marketing approval in the US and Europe [6].
Feb 17The EMA categorises PLX-PAD as an ATMP as it is both a somatic cell therapy medicinal product and tissue engineered product; based on that is considered as Tissue Engineered Product [5].
Feb 17PLX PAD is a designated EMA Adaptive Pathways pilot project for the treatment of critical limb ischaemia [2].
Jan 11Design of mutinational PII/III study agreed with EMA and FDA [1].

Category

Allogeneic ex-vivo expanded placental mesenchymal-like adherent stromal cells that stimulate the body to heal. Given as two i.m doses (each comprising 30 injections), 2 months apart. An ‘off-the-shelf’ tissue-engineered ATMP, needing no tissue matching.
Approximately 20% of people aged over 60 years have some degree of peripheral arterial disease, with greater prevalence in people with cardiovascular disease and risk factors such as diabetes, smoking and dyslipidaemia. Critical limb ischaemia occurs in around 1% of all people with peripheral arterial disease, with an estimated annual incidence of between 50 and 1,000 new cases per million population [3].
Critical limb ischaemia with minor tissue loss for patients with peripheral arterial disease or muscle injuries who are unsuitable for revascularisation
Intramuscular

Further information

Yes
Has been prioritised

Trial or other data

Aug 20PIII PACE trial (NCT03006770) is still recruiting subjects. Collection of primary outcome data is delayed and now expected to complete in Dec 21 [16].
Apr 20Emiplacel has been prioritised for potential TA guidance production. Topic has been passed to scoping team to prepare for a consultation exercise [16].
Dec 19No UK trial sites [10].
Dec 18PIII PACE trial (NCT03006770) is still recruiting subjects, with estimated primary completion date of May 2020 [8].
Feb 17PIII (NCT03006770) study is due to open for recruitment. This will be a randomized, placebo-controlled, parallel group, multicenter study. The study aims to evaluate efficacy, tolerability and safety of intramuscular injections of PLX PAD for treatment of 246 adults with CLI with minor tissue loss (Rutherford Category 5) who are unsuitable for revascularization. Primary outcome is Amputation Free Survival (AFS) up to 36 months from enrollment. Collection of these data is expected to complete Feb 20 [4].
Jun 15A PI/II (NCT01525667) study to assess efficacy and safety of local administration of PLX-PAD single dose, intra-muscular injection for the regeneration of injured gluteal musculature after Total Hip Arthroplasty (THA) completes. 20 adults were enrolled in Germany [4].
Jan 11The EMA and FDA have agreed on the design of a PII/PIII study. It will be a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel study. Patients with critical limb ischaemia (CLI) Fontaine class III-IV, Rutherford category 4-5, will be treated with two PLX-PAD treatments or with two placebo treatments, a few months apart, administered by multi-intramuscular injections delivered to the affected leg. The primary endpoint will be major-amputation free survival rate (amputations and death) at 12 months [1].
Jan 11PLX (PLacental eXpanded) cells are a drug delivery platform that release therapeutic proteins in response to a variety of local and systemic inflammatory diseases. PLX cells do not require tissue matching or immune-suppression treatment prior to administration [1].

Evidence based evaluations

1 January 2018NIHR