The FDA system is way too slow, we need more efficient genetic analysis when a drug works in some patients and not in others and testing in the patients most likely to succed.
CHRONIC HEART FAILURE MPC-150-IM is a Phase 3 product candidate being developed as a treatment for both advanced and end-stage chronic heart failure (CHF).
Disease Indication and Patient Population
CHF is characterized by an enlarged heart and insufficient blood flow to the organs and extremities of the body. The condition, which affects 2% of the adult population of the United States, is progressive and can be caused by many factors that put an excess demand on the heart muscle such as high blood pressure, faulty valves, infections or congenital heart problems. CHF prevalence is expected to grow 46% by 2030, affecting more than 8 million Americans1.
CHF is classified in relation to the severity of the symptoms experienced by the patient. The most commonly used classification system was established by the New York Heart Association (NYHA) and ranges from Class I (mild) to Class IV or end stage (severe).
Patients with advanced or Class II/III heart failure disease continue to represent the greatest unmet medical need despite recent advances in new therapies.
MPC-150-IM
MPC-150-IM is a tier 1 product candidate which consists of 150 million mesenchymal precursor cells (MPCs) administered by direct injection into the heart muscle in patients suffering from CHF and progressive loss of heart function.
Mechanism of Action
MPCs release a range of factors when triggered by specific receptor-ligand interactions within damaged tissue. Based on preclinical data, it is believed that these factors induce functional cardiac recovery by simultaneous activation of multiple pathways, including induction of endogenous vascular network formation, reduction in harmful inflammation, reduction in cardiac scarring and fibrosis, and regeneration of heart muscle through activation of tissue precursors.
Clinical Trials
Ongoing Phase 3 Trial
Approximately 600 patients are being enrolled in a placebo-controlled Phase 3 trial to evaluate a single dose of MPC-150-IM in Class II/III CHF patients across multiple sites in North America. Patients with advanced heart failure are expected to constitute the majority of the patients enrolled in this clinical trial program.
The objectives of this Phase 3 events-driven trial are to evaluate the ability of MPC-150-IM to reduce the primary endpoint of recurrent non-fatal heart failure-related major adverse cardiac events (HF-MACE) in patients with left ventricular dysfunction, as well as delay or prevent disease progression to end-stage HF and terminal cardiac events, defined as death, left ventricular assist device (LVAD) implantation, or cardiac transplant.
In April 2017, the trial achieved a successful pre-specified interim futility analysis of the efficacy endpoint in the first 270 patients and an independent data monitoring committee formally recommended the continuation of the trial.
A Phase 2 dose-ranging study in patients with Class II/III (New York Heart Association) heart failure has been completed. Click here for clinical trial results.
End-Stage Heart Failure
MPC-150-IM is also under clinical investigation for the treatment of end-stage heart failure.
In the United States, there are approximately 250,000–300,000 patients annually who suffer from advanced systolic heart failure (NYHA Class IIIb–IV) who despite optimal medical therapy (excluding mechanical assist devices) have a one-year mortality >25% and exceeding 50% in class IV patients.1 The only options to increase survival in these patients are the use of cardiac assist devices or heart transplants. Due to the decline in organ donations and limited availability of healthy donor hearts, the treatment of CHF with mechanical circulatory support devices such as LVADs is gaining momentum, with 4,500–5,500 assist devices implanted annually in the United States.2,3,4 However, rehospitalization is frequent in patients with an LVAD ranging from 2.1–2.7 times per year. The majority of patients rehospitalized for non-device related causes are as a result of GI bleeding (34%-44%) and infections (36%-44%).5,6
Clinical Trials
Phase 2 Trial
Results of a 159-patient randomized placebo-controlled Phase 2 trial, sponsored and conducted by United States National Institutes of Health (NIH), evaluating MPC-150-IM in the treatment of end-stage heart failure patients implanted with a left ventricular assist device (LVAD) were presented at the 2018 American Heart Association Scientific Sessions.
Key outcomes:
The trial succeeded in achieving the clinically meaningful outcome of reduction in gastrointestinal (GI) bleeding and related hospitalizations Results confirmed the previous pilot trial, which also demonstrated significant reduction in GI bleeding and related hospitalizations in MPC-150-IM treated LVAD patients Pilot trial results formed the basis for the FDA Regenerative Medicine Advanced Therapy (RMAT) designation granted in December 2017, which aims to expedite the development of regenerative medicine therapies intended for the treatment of serious diseases and life-threatening conditions Mesoblast intends to meet with the FDA to provide full study data and discuss the pathway to potential Biologics License Application (BLA) filing using reduction in GI bleeding and related hospitalizations as an approvable regulatory endpoint While the trial did not meet the overall primary endpoint of temporary weaning, MPC-150-IM treatment did significantly improve weaning in the 44% of patients with chronic ischemic heart failure LVAD patients with ischemic heart failure closely resemble the majority of patients enrolled in the ongoing Phase 3 trial of approximately 600 patients with moderate/ advanced heart failure. Pilot trial results
The results of the pilot trial were presented at the American Heart Association Scientific Sessions 2013 and published in the journal Circulation in June 2014. Click here more information on the trial results.
1Gustafsson F, Rogers JG. Left ventricular assist device therapy in advanced heart failure: patient selection and outcomes. European Journal of Heart Failure 2017;19:595-602
2United Network for Organ Sharing
3Agency for Healthcare Research and Quality – Healthcare Cost and Utilization Project – Claims Analysis ICD- 37.6
4Data on file
5Chatterjee A, Feldmann C, Hanke JS (2018) The momentum of HeartMate 3: a novel active magnetically levitated centrifugal left ventricular assist device (LVAD). J Thorac Dis 10 (Suppl 15): S1790-S1793
6Mehra, MR Salerno C, Cleveland JC (2018) Health care resources use and cost implications in the MOMENTUM 3 long-term outcome study: a randomized controlled trial of a magnetically levitated cardiac pump in advanced heart failure
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