Jordan Report

Jordan hosts ground-breaking
stem cell trial for
heart repair

Bioheart has turned to Jordan to conduct an important clinical trial of its pioneering genetically modified MyoCell product because it is more affordable and they consider the kingdom’s medical practise to be on a par with some of the leading medical research facilities in the United States. Callan Emery reports.

The Jordan Hospital in Amman, Jordan, will play host to a ground-breaking clinical trial on patients with congestive heart failure. The US FDA-approved study, REGEN, is set to observe 15 patients with congestive heart failure treated with MyoCell SDF-1, a genetically-modified version of MyoCell, in a process that uses the patient’s own muscle cells as a basis for treatment.

Speaking to Middle East Health, Peggy A. Farley, Chief Operating and Financial Officer of Bioheart, the company that has funded the development of MyoCell, explained that they decided to conduct the research in Jordan – although the results would be submitted to the US FDA – because the costs of conducting this trial in the US were prohibitive. She added that Jordan became an attractive option because the quality of medical practice at certain hospitals in the country was on a par with the top clinical centres in the US.

“The REGEN trial is a Phase I study to determine the optimal dosage for MyoCell SDF-1 to treat congestive heart failure,” Farley said.

MyoCell SDF-1 is a genetically modified version of MyoCell. MyoCell is a regenerative cell therapy that uses myoblasts, or muscle stem cells that are grown from a patient’s own muscle. MyoCell has been tested successfully on patients in four clinical trials.

“MyoCell, itself, has been shown to be safe and effective at the levels of 400 and 800 million cells injected into the heart of a congestive heart failure patient. We want to see whether the same levels of MyoCell SDF-1 are appropriate as a treatment. Once we have observed the effect of escalating levels of MyoCell SDF-1, we will incorporate MyoCell SDF-1 into our ongoing Phase II/III MARVEL trial,” Farley said.

The MARVEL trial is designed to assess functional capacity and quality of life in patients with advanced heart failure after receiving injection of adult muscle stem cell therapy – MyoCell – in their damaged heart muscle. Phase 1 is complete. The FDA has given clearance to go ahead with a Phase II/III trial of MyoCell in North America and Europe.

“The costs for conducting a clinical trial in the United States are prohibitive,” Farley said. “For the REGEN study, which is only on 15 patients, we would have incurred a cost of US$2 million or more. At this juncture, with capital investment very tight in the United States, if limited to the United States, we would not have had the financial resources necessary to do the study.

“We decided to look for alternatives to the conduct of the study in the US. At this point, there are a number of alternatives, including China and India. We chose Jordan because the practice of medicine in Jordan rivals that of the top clinical centres in the United States. The physicians in Jordan are on a par with the best US physicians in each specialisation and Jordan’s best facilities mirror those in the United States.

“Furthermore, unlike other countries, Jordan rigorously observes methods and standards for data gathering that comply with international standards that are also observed in the United States so that we can rely on those data with confidence. We are, therefore, able to conduct a study in Jordan that will be equal to or possibly surpass the quality of the same study if it were conducted in the United States.”

Leading the study at the Jordan Hospital is Dr Imad Alhaddad, MD, FACC, FACP and Co-Director of the Jordan Cardiovascular Centre. He is also Principal Investigator.

He explained that Jordan Hospital was an excellent place to conduct this research as it is a tertiary referral hospital for complex cardiovascular disease and  the Cardiovascular Center is a comprehensive and state of the art facility run by internationally known consultants. Farley said they were “very pleased that Dr Alhaddad has consented to be the Principal Investigator for the study and that Jordan Hospital has agreed to be the study centre.

“We are hoping that the Royal Medical Services Hospital will be a second centre for us. Both hospitals are excellent.” Discussing the trial, Dr Alhaddad said that until now heart muscle damage was considered irreversible and permanent. “As a result of the trials, we can now help regenerate and repair heart muscle using innovative techniques like stem cell therapy. The REGEN trial is a milestone study that will help us achieve these goals.”

Dr Alhaddad told Middle East Health that they were due to start the recruitment process and that they exoected the trial to be completed within a year.

“This is a phase 1 trial primarily designed for dose finding and safety. We hope to demonstrate similar benefits to preclinical studies,” he said.

Preclinical animal studies showed a 54% improvement of heart function with modified myoblasts as compared to 27% for the animals treated using myoblasts without modification.

Dr Karl Groth, Chairman and CEO of Bioheart, explained that research “conducted in advance of pre-clinical trials strongly indicates that genetically modified stem cell therapy may increase the speed of repair or regeneration of heart muscles. This means that a patient can return to a normal lifestyle, faster.”

“We have found that SDF-1 releases additional therapeutic proteins to assist in the tissue repair process, resulting in a more expansive and quicker repair.”

Groth added that the REGEN trial is designed to test the safety and effectiveness of the composition of muscle stem cells that have been gene-modified to induce a greater than usual release of the SDF-1 protein.

“We fully expect that this trial will significantly enhance the clinical improvements we have already observed in our Phase II/III MyoCell study,” Groth said.

He explained that unlike other tissues, the heart muscle does not release sufficient SDF-1 to attract the number of stem cells to promote complete self-healing, often resulting in scar tissue formation and an impairment of normal heart function.

Asked when a MyoCell product could be commercialised Farley said that if the REGEN trial is successful “the next step towards commercialisation in the US is to incorporate MyoCell SDF-1 into our Phase II/III MARVEL trial for US FDA approval. That study is on hold pending the outcome of the REGEN trial. We expect the MARVEL trial to be completed roughly 18 months after its continuation. Assuming that it begins again in mid-2011, it would be completed in 2013, with commercial product launch during that year, assuming rapid approval by the US FDA.

“Outside the United States, we are establishing Centres of Excellence where patients have access to our treatments for congestive heart failure, acute myocardial infarction, chronic heart ischemia, and lower limb ischemia. Once we have completed the REGEN trial, and have assessed optimal dosage, we will make this treatment available to our centres so that congestive heart failure patients can benefit from the treatment. Since we use autologous muscle cells (cells taken from the patient’s own muscle) as the basis for the treatment, we do not have issues of rejection or safety.

“And, in many countries other than the United States, that fact is sufficient to allow treatment within those countries.”

What is MyoCell and how does it work?

MyoCell is a regenerative cell therapy that uses myoblasts, or muscle stem cells that are grown from a patient’s own muscle. Modified myoblasts induce a higher release of SDF-1 protein, the catalyst that generates stem cells in the body after an injury.

Following a heart attack – congestive heart failure – the body naturally increases the level of SDF-1 protein in the heart, but not enough to heal the damaged tissue. By modifying the myoblasts to express additional SDF-1, the SDF-1 protein levels present in the heart are multiplied exponentially.

The additional quantities of SDF-1 protein stimulate the recruitment of the patient’s existing stem cells to the cell transplanted area.

The recruited stem cells will assist in the tissue repair and blood vessel formation process.

The treatment with MyoCell involves taking a biopsy from the patient’s leg muscle, transporting that biopsy to Bioheart’s cell manufacturing facility, expanding the number of cells from the biopsy, and inducing the cells to regress to produce precursors to muscle cells called myoblasts. These cells know that they are muscle cells, but do not know which muscle.

Once those precursor cells, or myoblasts, are present, they are segregated from the muscle cells and grown until they number over 1 billion cells. The myoblasts are then transported back to the patient’s treatment centre. Some are then injected into the patient’s heart with a needle-tipped injection catheter. The treatment used in the REGEN trial involves genetically modifying myoblasts (MyoCell SDF-1), utilising Bioheart’s proprietary process.

The modified cells are injected in the same manner into the patient’s heart. The myoblasts release increased levels of the SDF-1 protein, which stimulates angiogenesis and regeneration of tissue.

ate of upload: 15th Aug 2010

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