dm+d

Unassigned

New Medicines

Revascor Advanced chronic heart failure in patients who are no longer responsive to maximal standard of care heart failure drugs

Information

Revascor
New molecular entity
Mesoblast
Mesoblast

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Jul 21Mesoblast has filed requests and expects to hold meetings with the FDA during the next two quarters to discuss the pathways to US regulatory approval. No plans for submissions to European regulators announced for the heart failure indication (Mesoblast does plan to meet with the EMA to discuss a licence application for chronic discogenic lower back pain). Presume no plans for a UK licence at this time [18].
Mar 21Mesoblast intends to meet with FDA to discuss a potential pathway for approval of rexlemestrocel-L in patients with chronic heart failure based on the observed reduction in mortality and morbidity in the chronic heart failure Phase 3 trial. It is in ongoing discussions with potential strategic partners to develop and commercialise rexlemestrocel-L [17].
Nov 20PIII trial has completed patient follow-up and all events have been independently adjudicated. While the COVID-19 pandemic has delayed completion of data quality review at the study sites, trial data readout is expected in the current quarter [14].
Apr 20Data readout for PIII trial in advanced CHF planned for mid-2020; results may support regulatory approval in the US. No plans for EU approval described yet [13].
Jun 16Mesoblast notes that the US and Europe are leading markets for rexlemestrocel-L [1].
Jun 16FDA approves use of a second navigational catheter system in Mesoblast´s PIII program for advanced heart failure. Over 2,000 of these FDA-approved systems are currently in use across the US for treating atrial fibrillation, and their use in the Mesoblast program is likely to result in accelerated PIII trial recruitment and potentially a simplified distribution process through existing commercial channels once the product is approved [1].
Jun 16Mesoblast regains full worldwide rights from Teva [1].

Category

An allogeneic mesenchymal precursor cell (MPC) product
The unadjusted prevalence of heart failure is 0.7% of all patients registered with a GP in England and there were 61,130 admissions for heart failure (ICD10 I50) in 2011-12 [3,4].
Advanced chronic heart failure in patients who are no longer responsive to maximal standard of care heart failure drugs
Intracardiac

Trial or other data

Jan 21In the DREAM-HF trial in patients with chronic HF and reduced LVEF (n=537), a single dose of rexlemestrocel-L was associated with a reduction in three-point MACE over a median of 30 months (20.6% v 30%; p=0.027) [16].
Apr 20PIII DREAM HF-1 study recruited patients in the US & Canada - there were no UK trial sites. Collection of primary outcome data is due to complete end of May 20 [12].
Mar 20After surpassing the number of primary endpoints required for completion of the PIII DREAM HF-1 (NCT02032004) trial of REVASCOR for advanced chronic heart failure, final study visits for all surviving patients have been initiated in this CV outcomes trial in 566 patients. The independent Data Monitoring Committee overseeing the PIII trial held its 10th and final scheduled meeting and recommended that the trial continue as planned. The DMC reviewed available data from the 566 randomised patients, including components of the primary and secondary endpoints, and all safety data. The PIII trial results will be considered pivotal to support regulatory approval in the US [11].
Jun 16In a completed PII trial, patients treated with MPC-150-IM had no HF-MACE over 36 months of follow-up, compared with 11 recurrent HF-MACE events in the control group (p100ml, who closely resemble the patients being recruited in the Phase 3 trial, 71% of controls had at least one HF-MACE event vs 0 of those who received a single injection of MPC-150-IM (p<0.001) [1].
Jun 16The pivotal PIII trial is now close to 40% recruited, and is scheduled for completion within eighteen months [1].
Jan 16To shorten the time of trial completion, the pivotal PIII trial size has been reduced to 600 patients. The primary endpoint of the trial was also revised, and revised primary endpoint was a comparison of recurrent HF-MACE between patients treated with rexlemestrocel-L and controls. The revision of endpoint was supported by the fact that a single injection of rexlemestrocel-L successfully prevented recurrent HFMACE over three years in a PII trial. The reduction in trial size and endpoint revision was preceded by the communications between Teva and the US FDA. After reviewing the clinical data of the first 175 patients from the trial, in April 2016, the Data Monitoring Committee (DMC) recommended the continuation of the trial as per the protocol [2].
Jan 14Teva initiate a pivotal PIII trial assessing the efficacy, safety and tolerability of rexlemestrocel-L in adult and elderly patients with chronic heart failure (NCT02032004). The primary endpoint of the randomised, double-blind, placebo-controlled trial is the time to first heart failure-related major adverse cardiac events (HF-MACE) assessed over 5 years. The trial is designed to enrol approximately 1,165 patients, with high NT-proBNP levels and a heart failure-related hospitalisation within the past nine months. The trial is underway in the US, Canada, Latvia, Lithuania, Spain, and the UK [2].

Chronic low back pain in adults

Information

Licence extension / variation
Grunenthal
Mesoblast

Development and Regulatory status

None
None
Phase III Clinical Trials
Jul 21Mesoblast and its partner in Europe and Latin America, Grünenthal, amend their collaboration agreement in line with a strategy to achieve regulatory harmonisation, cost efficiencies and streamlined timelines aiming to leverage the results from a planned US trial in support of potential approval in both US and EU. Mesoblast has filed requests and expects to hold meetings with the FDA during the next two quarters to discuss the pathways to US regulatory approval [6].
Mar 21Mesoblast intends to meet with the FDA to discuss a potential pathway for approval of rexlemestrocel-L in patients with chronic discogenic lower back pain based on the observed durable reduction in pain and opioid sparing activity in the CLBP PIII trial. It is in ongoing discussions with potential strategic partners to develop and commercialise rexlemestrocel-L [5].
Nov 20While the COVID-19 pandemic has delayed completion of data quality review at study sites, data readout for the US PIII trial in 404 patients is expected in the current quarter. Mesoblast continues to collaborate closely with Grünenthal on the clinical protocol for a confirmatory PIII trial in Europe for MPC-06-ID in chronic low back pain due to degenerative disc disease, with the results of this and the US PIII trial expected to support both FDA and EMA regulatory approvals [4].
Apr 20Mesoblast has plans to obtain clearance from European regulatory authorities to begin a European PIII trial and subsequently initiate that confirmatory in partnership with Grünenthal [3].
Mar 20The companies have agreed on an overall development plan for the product to meet European regulatory requirements. As part of this plan, they are collaborating on the study design for a confirmatory Phase 3 trial in Europe, with the results of the two Phase 3 trials expected to support both FDA and European Medicines Agency regulatory approvals for MPC-06-ID [3].
Sep 19Mesoblast and Grunenthal enter into an alliance for the development, manufacture and commercialisation of rexlemestrocel-L in Latin America and Europe for chronic lower back pain [3].

Category

An allogeneic autologous mesenchymal precursor cell (MPC) product
Back pain is extremely common. 60-80% of people in the UK report back pain at some time in their lives. A UK population-based cross-sectional study of people aged 25 years and older found the one-month period prevalence of low back pain to be around 30%, peaking at age 41-50 years. The one-year prevalence of chronic low back pain is about 1% [1].
Chronic low back pain in adults
Intradiscal
Parenteral

Trial or other data

Mar 21In its latest operational highlights report, Mesoblast announces that results from PIII trial of rexlemestrocel-L (MPC-06-ID) showed that a single injection of rexlemestrocel-L + hyaluronic acid (HA) carrier may provide at least two years of pain reduction, with opioid sparing activity in patients using opioids at baseline. Significant and durable reductions in CLBP through 24 months were seen across the entire evaluable study population, and greatest pain reduction was observed in the pre-specified population with CLBP of shorter duration than the study median of 68 months. The results indicate that treatment benefit may be greatest when inflammation is high and before irreversible fibrosis has occurred in the intervertebral disc [5].
Mar 20In PIII trial of MPC-06-ID in 404 patients with chronic low back pain due to degenerative disc disease (NCT02412735), final study visits for all evaluable patients have been initiated [3].
Aug 19PIII study (NCT02412735) is no longer recruiting [2].
Mar 15PIII study to evaluate the safety and efficacy of rexlemestrocel-L alone or combined with hyaluronic acid (HA) in subjects with chronic low back pain (> 6 months) associated with moderate radiographic degenerative changes of a disc starts (NCT02412735). 404 adults will be recruited in the US and Australia. Primary outcome is treatment success at 24 months (composite responder analysis of low back pain Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) score and no post-treatment interventions); collection of these data is due to complete Mar 20 [2].

Revascor End-stage heart failure in people who require a left ventricular assist device

Information

Revascor
Licence extension / variation
Mesoblast
Mesoblast

Development and Regulatory status

None
None
Phase II Clinical Trials
Yes
Apr 20In its latest financial report, Mesoblast planned key milestones include initiating the confirmatory PIII trial of Revascor in end-stage heart failure patients with an LVAD [7].
Mar 20Mesoblast ’s intellectual property portfolio encompasses approximately 1,000 patents or patent applications across 68 patent families, which it believes will provide substantial competitive advantages for the commercial development of its cell-based therapies in major markets including the U.S., Europe, Japan and China [6].
Nov 19Mesoblast announceds that they and the International Center for Health Outcomes Innovation Research (InCHOIR) at the Icahn School of Medicine at Mount Sinai in New York have greed on the protocol in line with the US FDA guidance for a confirmatory PIII trial in patients with end-stage HF and a LVAD. Both parties agreed with the FDA on a primary endpoint of reduction in major mucosal bleeding events, and key secondary endpoints demonstrating improvement in various parameters of CV function [2].
Jun 19US FDA grants orphan drug status to rexlemestrocel-L for prevention of post-implantation mucosal bleeding (including gastrointestinal bleeding) in end-stage CHF patients who require a LVAD [2].
Dec 17Granted Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of heart failure in patients with left ventricular systolic dysfunction and left ventricular assist devices. The designation was based on data from a pilot clinical trial in 30 patients [2].

Category

An allogeneic autologous mesenchymal precursor cell (MPC) product
The British Heart Foundation estimates that 900,000 people in the UK live with definite or probable heart failure, and a further 68,000 people develop the condition each year recent study found that 14% die in the first six months (38,000 men and around 30,000 women). A 2009 study found that 14% die in the first six months. The average life expectancy is only about three years following a diagnosis [1].
End-stage heart failure in people who require a left ventricular assist device
Intracardiac

Trial or other data

Apr 20In England, the implantation of a VAD may be considered in patients with advanced heart failure who are listed for a transplant and who are deemed to be deteriorating so rapidly that they would not survive long enough to receive a heart via the urgent allocation scheme. A short-term VAD can be used as a bridge to decision in extremely sick or ‘moribund’ patients who have contraindications to the implantation of a long-term VAD or urgent transplantation at the time of presentation. Contraindications must be considered acute and potentially reversible. CCGs commission care for patients who are on ambulatory mechanical circulatory support (older children and adults) whilst waiting for a heart transplant unless the patient requires care from a specialised service [8].
Aug 19PIIB study (NCT02362646) completes [3].
Mar 19The company receives guidance from the US FDA that the results from the PIIb study (NCT02362646) could support marketing approval [2].
Nov 18Mesoblast Ltd announced topline results from a PII randomised, sham-controlled trial (n=159) in pts with end-stage heart failure implanted with a left ventricular assist device (LVAD). Injections of MPC-150-IM (mesenchymal precursor cells) into the myocardium when the LVAD was implanted did not acheive the primary endpoint of temporary weaning from full LVAD support. This was thought to be due to blood clots in the devices that reduced the number of attempts. However, the therapy did allow a subgroup of pts with ischemic HF to be weaned off the LVADs temporarily, and there was a significant 76% reduction in major GI bleeds plus a 65% drop in bleed-related hospitalisations in pts treated with the therapy compared to the control gp (p=0.02) [4,5].
Jul 15PIIb study to evaluate the safety and efficacy of rexlemestrocel-L on the myocardial function in patients with heart failure who are recipients for LVAD implantation (NCT02362646). The primary endpoint of the trial is to improve heart function and reduce the need for LVAD implantation and will also evaluate patient survival and re-hospitalisation over 12 months. 159 adults will be recruited in the US and Canada; no UK trial sites [3].
Aug 14PIIb trial of rexlemestrocel-L in patients with end-stage CHF requiring mechanical circulatory support starts. The study intends to enrol approximately 120 patients in the US. This was following positive results from a pilot trial in 30 patients with heart failure who received LVAD were released in Jun 14 [2].