Mesoblast recently completed enrollment for its double-blind, placebo-controlled Phase 2 clinical trial at multiple sites across the United States and Australia to randomize 100 patients with intervertebral disc disease to receive either high doses of the company's allogeneic MPCs with hyaluronic acid carrier, hyaluronic acid carrier alone or saline solution.
"A theoretical advantage of this treatment is that if we are able to help a disc repair itself, then presumably we'll reduce the patient's chronic low back pain and associated disability, the need for oral pain medications, and absence from work," says Michael J. DePalma, MD, president and medical director of Virginia iSpine Physicians where he practices interventional spine care and Director of Research at Virginia Spine Research Institute. "Not everyone with a painful disc would be a candidate; patients with severe degeneration or significant mal-alignment would not be candidates. This technology seems to fit within the spectrum of treatments for patients, but the challenge is defining the appropriate candidate."
Depending on final results of this study, Mesoblast may advance to a larger clinical trial to prove its effectiveness. "We really need a therapy like this," says Hyun Bae, MD, medical director and director of spine education at Cedars-Sinai Spine Center. "We don't currently know what to do with these patients; surgery sounds like a big hurdle to them, so we do other therapies to try to help. I think Mesoblast has great promise because we can take these patients and return them to regular activity without surgery."
Back pain currently impacts 84 percent of adults, which can evolve into chronic low back pain. Chronic low back pain is expensive to treat and there is a huge economic loss associated with those patients. Current research publications internationally identify the intervertebral disc as the leading source of low back pain in the vast majority of patients.
"The problem is often an intervertebral disc develops an internal wound that does not heal properly," says Dr. DePalma. "Part of the body's reaction to the wound is an attempt to heal, but the healing process within the injured disc can be dysfunction leading to degeneration over time. We don't have a 'home run' treatment for those discs yet. We can provide pain relief by injecting steroids around the disc, but that doesn't fix the problem. We want to promote tissue healing within the disc."
The stem cells included in the Mesoblast injection may promote healing, but not just because they are stem cells. Researchers and scientists developed a method to isolate the right cells to achieve the desired affect.
"The more basic science research you do on stem cells, the more you realize that stem cells are not created equally," says Dr. Bae. "Just because it's a stem cell doesn't mean it's going to regenerate the desired tissue. You can find stem cells in many places — in fact, you can take stem cells in circulating blood, bone marrow or fat and spin them down, but they may never produce the results you want. In our own research, we not only have to isolate the best cell in a population of millions of stem cell but also have to modulate them with small molecules or drugs to get the desired effect."
In the Phase 2 Mesoblast trial, surgeons are injecting the purified mesenchymal precursor cells that have been expanded in the lab into their patients. Dr. Bae compares different concentrations of the stem cell injection with saline to determine whether Mesoblast has a positive impact on healing. The patients and investigators are blinded but the recent results of the Phase II trial show a positive impact in patients treated with stem cells over saline.
"The prevailing logic is that these cells have the ability to detect injury within the disc and respond to local stimuli of inflammation in the tissue that can induce the cells in the body to regenerate and proliferate," says Dr. DePalma. "That will promote a healing state in the disc."
At the 12-month mark, a greater proportion of the patients injected with Mesoblast experienced a 50 percent reduction of back pain when compared with patients who underwent injections of the control substance. A greater portion of the Mesoblast patients reported minimal residual back pain after one year. The study will continue to the 36-month mark.
"The trials will have to demonstrate true advantage of stem cell treatment over placebo in order to obtain FDA approval," says Dr. Bae. "This treatment will also have to show cost effectiveness and utility to justify payment from private insurance carriers."
While FDA clearance is still a ways off, the trials allow spine specialists surgeons to draw preliminary information about the future of treatment. Based on the initial results, there may be reason to move forward with a more rigorous trail to corroborate the initial results.
"Following the regulatory process, we would have to accept the initial results as a foundation for moving forward with a larger study, but it could be three to five years before the study would be completed," says Dr. DePalma. "Pending positive results, we may then see this new technology available for patients on a routine basis."
While the current outlook is shiny, Dr. Bae recognizes the placebo effect can be strong. He's worked in other clinical trials where patients had very promising results, only to find out the treatment had little advantage over the placebo when the data was unblinded.
"If I say I'm going to inject you with something that may help, there's a high likelihood you'll have a positive demonstrable effect," says Dr. Bae. "The Mesoblast trial was done against a placebo and in the phase 2 of the trial Mesoblast patients had better outcomes than the saline placebo group. For a treatment to show beneficial effects above a blinded placebo is an incredibly difficult task."
The clinical data may indicate a larger trial would be beneficial, but there is a huge cost. The larger clinical trials can cost $40 million to $50 million, and outside funding is scarce. However, if the therapy proves effective and becomes available to a wider patient population, it could have a positive impact on the economics of back pain.
"Mesoblast would allow us to intervene earlier with a treatment that has a proven effect," says Dr. Bae "We have a lot of tools in our armamentarium, such as chiropractic care or epidurals, and they are great to optimize patients, but I would like to have a therapy that's delivered easily and could be better. I think regenerative therapy is the focus of the new millennium; it's no longer replacement or reconstruction, but regeneration."
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