Does the Placenta Hold the Answer to One of Our Most Challenging Medical Problems?
Bloomberg.com
Dec 10, 2018 - 12:00 AM
The placenta, a vital organ that supports the earliest stages of human development, now offers millions of patients the chance of a better quality of life following a scientific breakthrough that could save healthcare systems billions of dollars annually.

A clinical study of a pioneering placenta-based cell therapy product, PLX-PAD, has shown that it can dramatically enhance the mobility of patients with peripheral arterial disease (PAD) in their legs, and greatly reduce, or even eliminate, their need for surgery and hospitalization.

The implications of the statistically significant findings are considerable.

Peripheral Artery Disease is an increasingly common circulatory problem in which narrowed arteries reduce blood flow to your limbs. When you develop peripheral artery disease (PAD), your extremities do not receive enough blood flow to keep up with demand. Patients with PAD are at high risk of heart attack, stroke and cardiovascular death. It is estimated that more than 200 million people suffer from PAD today, and the figure continues to grow.

PAD, caused by fatty deposits in leg arteries, afflicts around 20 million American patients, 28 million Western Europeans and up to 60 million Chinese. PAD is estimated to affect 15—20 percent of people over 70 years of age, and its prevalence is set to grow in countries with rapidly aging populations. Risk factors include smoking, diabetes, obesity and stress. The commercial value of a viable treatment for the condition is likely to run into several billion dollars annually.

The rising prevalence of the disease is a major concern and is fueling a global PAD market valued at $3.14 billion in 2016. The market is projected to reach $4.98 billion by 2023, growing at a CAGR of 6.8 percent, according to Allied Market Research as innovative companies turn to biotechnology to meet the currently unmet medical needs.

The clinical results are potentially of profound importance for healthcare systems around the world, given the scale of the disease, its likely growth in populations worldwide and the fact that PAD patients currently spend large amounts of time in the hospital. By increasing the mobility of these patients, the cell therapy can also relieve depression and further alleviate costs for healthcare services.

PLX-PAD is a cell therapy product developed by Israel-based Pluristem Therapeutics (NASDAQ: PSTI), which uses placenta cells to create products that can be mass-produced and administered by intra-muscular injection. The placenta-based cell-therapy products release soluble biomolecules that heal damaged tissue and encourage generation of blood cells. Current alternative treatments include revascularization surgery to restore the blood supply in the limb, a process that involves lengthy hospitalization and is unsuitable for many PAD patients, including those with diabetes.

“Finding a nonsurgical medical solution for PAD, especially in patients who are unsuitable for revascularization, has proven to be one of the biggest medical challenges in recent years. Pluristem’s recent study results are highly encouraging and suggest that PLX-PAD cells may be the answer for both PAD patients and physicians seeking effective medical solutions,” says Professor Norbert Weiss, M.D., Director of the Vascular Center at the Technical University of Dresden, and the lead principal investigator for the European part of the study.

Research took place at 28 clinical sites in the United States, Germany, South Korea and Israel, and involved 172 patients with intermittent claudication (IC), a stage of PAD. The study examined the impact of PLX-PAD on the ability of patients to walk, and found that those given two administrations of cells, taken from different placentas, increased their maximal walking distance by 83 percent after 52 weeks. The same group also reported a zero requirement for revascularization treatment over a 65-week period.

Crucially, the findings provide validation for an ongoing Pivotal Phase III study of the treatment for the more extreme form of PAD, critical limb ischemia (CLI), which leaves patients in pain even when at rest, and include skin wounds and a high risk of leg amputation and death.

Dr. Manesh Patel, Chief of the Division of Cardiology at Duke University Health System and the lead principal investigator for the U.S. part of the IC study, describes the latest findings as an “important outcome” for the use of advanced regenerative medicine technologies. “We look forward to the CLI pivotal study results that may demonstrate the ability of Pluristem’s cell therapy to improve patient outcomes and create economic benefits for healthcare systems,” he says.

Yaky Yanay, Co-CEO and President of Pluristem, says that despite its “huge number,” the PAD population often goes unnoticed by the general public, which tends to regard people with the disease as merely suffering the effects of old age.

“We are looking at a long-term chronic disease,” he says. “Even the most simple things, like wearing shoes and walking, are difficult for them. It means that these patients are not mobilized, and because they are elderly, they are often not involved in society, which leads to a high incidence of depression. Some call them the invisible patients, because today the healthcare system has no good solutions for them.”



For people suffering “severe and constant pain,” the results of this study give rare cause for optimism that their quality of life might soon improve. “What we have released is actually a high dose of hope for PAD patients,” says Yanay. “We are trying to regenerate the condition of these patients to allow them to go back to society, have a better quality of life and be able to do the simple things, like go downstairs and walk on the street—the things that most of us do without even thinking.”

Yanay notes that the cost to U.S. healthcare systems to treat PAD patients is already $20—25 billion a year. “As long as we are increasingly aging, this situation is becoming worse,” he says.

Part of the potential value of cell therapy is its capacity for intervention to ensure that patients with the milder IC condition do not deteriorate. Many CLI patients are ineligible for surgery because of diabetes or other complications, and they spend an average of 30 days in the hospital each year, also putting them in danger of infection.

Cell therapy treatment is “relatively simple,” Yanay explains. “You go to the clinic and do the treatment, which takes about 20 minutes, and you stay for two hours and then go back home. You come in again after two months, take the same course, and that’s it.”



The full-term placentas, which once would have been discarded as medical waste, are collected by partner hospitals with the consent of mothers, who, Yanay says, have been overwhelmingly supportive of the project. From each placenta, Pluristem is able to treat over 20,000 patients.

“We can provide patients with young, potent, healthy cells that are interacting with the body,” he says. “They will secrete a lot of therapeutic proteins that are supporting the regeneration of the blood transfusion into the patient’s leg, enabling it to function. Closing the wound, reducing the pain and allowing them to walk—that’s regenerative medicine.” He says that finding a solution for PAD patients is “no less than a mission” for Pluristem’s research teams.

The potential business opportunity for a company that finds an effective means of treating PAD is “enormous,” Yanay says. “Any company that can find a reasonable solution for CLI is looking at potential annual revenues of several billion dollars. We are looking at a very big opportunity.”

Pluristem has attracted major funding from the American and Israeli governments and from the European Union. The fact that regulators in these territories are supportive of Pluristem and its pivotal studies are providing it with accelerated pathways is an indication of the hunger for a solution to this problem, Yanay believes. “We are looking at going to market not in 10 years, but potentially two or three years from now, and in Europe it might be even earlier,” he says.

The company, which employs 200 people and devotes around a quarter of its staff resources to research and development, is also developing placenta-based therapies for the treatment of acute radiation syndrome (ARS) to alleviate the side effects of chemotherapy and radiotherapy, and to boost muscle regeneration among hip joint surgery patients.

Written by Ian Burrell, for Bloomberg Media Studios