Mito research around the world

Elamipretide (Bendavia, MTP-131)

What is Elamipretide?

Elamipretide, also known as Bendavia or MTP-131, is an injectable drug developed by a U.S based pharmaceutical company called Stealth BioTherapeutics.

It was initially developed to protect against a special type of tissue damage which is caused when there is a sudden return of blood to an organ after there has been a lack of blood (this commonly happens on recovery from a heart attack or following organ injury).

This damage is called ‘reperfusion injury’ and is caused when the mitochondria suddenly over-work to restore the balance in the cell. This can generate an overflow of damaging oxygen species, known as free radicals, which can trigger wide-scale tissue damage and cell death.

How does it work?

Elamipretide is a drug that reaches the inner mitochondrial membrane and targets part of the membrane critical to maintaining mitochondrial function. This is challenging because it is difficult to develop drugs that will pass through both the cell membrane and outer mitochondrial membranes.

What is it supposed to do?

Elamipretide is thought to normalize the structure of the inner mitochondrial membrane, which can lead to improvements in mitochondrial function. This can include improved energy production and a reduction in the formation of harmful free radicals. In turn, this is thought to increase energy supply and reduce cell damage and death.

Is it a cure?

Unfortunately not. Elamipretide cannot correct the underlying genetic defect that causes mitochondrial disease.

What types of mitochondrial disease could it treat?

Elamipretide is currently being trailed in patients with mitochondrial disease and muscle weakness (primary mitochondrial myopathy). It is also being trialed in patients with a mitochondrial disease known as Leber’s hereditary optic neuropathy (LHON).

Have there been any trials of Elamipretide?

A phase 1/2 clinical trial, known as MMPOWER, was performed to evaluate the safety, tolerability and efficacy of elamipretide in 30 patients with mitochondrial disease and mitochondrial myopathy. Initial positive results were published in 2016. The findings demonstrated statistically significant improvements in 'distance walked in six minutes', which is an accepted measurement of functional exercise capacity. This improvement was seen after five days of treatment with elamipretide.

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What is the latest update on this trial?

The results of a follow-on phase 2 clinical trial, known as MMPOWER2, were announced in June 2017. In this study, patients who took part in the initial MMPOWER trial were given elamipretide for a longer treatment period of four weeks. This showed further improvements in ‘distance walked in six minutes’, although the results were not statistically significant. Detailed analysis revealed that elamipretide had most benefit for those who were able to walk the shortest distance before treatment.

In March 2017, Stealth started a multi-national pre-trial registry of patients with mitochondrial myopathy called RePOWER. The aim of this was to obtain information that would help inform a phase 3 clinical trial and over 400 patients were enrolled across 29 sites (including 2 in the UK - London & Newcastle).

What next?

Patients enrolled in RePOWER were eligible for recruitment into MMPOWER3, a phase 3 randomized, double-blind, parallel-group, placebo-controlled trial to evaluate the efficacy and safety of daily injections of elamipretide in subjects with primary mitochondrial myopathy (PMM) followed by an open-label treatment extension. This 32 week trial will assess approximately 200 patients (ages 16-80) at approximately 30 sites in North America and Europe and is now fully-enrolled. Results are expected in late 2020.

Are there any other trials?

A phase 2 clinical study, known as ReSIGHT, is evaluating the safety, efficacy and tolerability of Elamipretide in the form of eye drops for the treatment of LHON.  The trial has 12 participants with a particular genetic mutation associated with LHON and involves twice-daily application of the drops for 52 weeks, with an option to enter an open label extension for up to 48 weeks of treatment.

Other Info

In October 2017, Stealth BioTherapeutics received Fast Track designation and Orphan Drug designation from the FDA in the US for the development of elamipretide for primary mitochondrial myopathy.  This aims to advance both the evaluation and development of drugs that have the potential to treat rare diseases and should make it easier for Elamipretide to gain marketing approval.

More information can be found here: https://www.stealthbt.com/

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