Despite the ongoing funding issues and political challenges, several companies are moving forward with clinical trials and
logging impressive early stage data. Last May, Osiris Therapeutics, an elder statesman in the stem cell space, secured the
approval of Prochymal in Canada, for the treatment of graft-vs-host disease in children who have received bone marrow transplantation.
The product received a second approval in New Zealand in June. Prochymal isn't the first stem cell therapy approved; Genzyme's
Carticel was the first FDA approved therapy, way back in 1997. The reason that Osiris can legitimately claim to be the first
approved stem cell "product" is because Carticel, and several other therapies approved globally, rely on an autologous procedure,
meaning that adult stem cells are extracted from the patient, and then readministered to the same patient. Autologous therapies
are limited, from a commercial standpoint, by the fact that cells must be derived from the individual adult patient that will
make use of them. Prochymal, on the other hand, utilizes human mesenchymal stem cells sourced from the bone marrow of healthy
adults ages 18 to 30, for use in other patients, a cell transfer process known as allogeneic transplant. Allogeneic therapies
are closer to products in the sense that they can be scaled and used by any number of people.
A critical success factor in other technologies in the healthcare field has been a very active NIH…one that is able to fund
early research. —Martin McGlynn
Autologous therapies have much to recommend them, however. Tim Mayleben, CEO at Ann Arbor, Michigan-based Aastrom Biosciences,
says primary market research conducted by his company found that autologous therapies, like Aastrom's Phase III candidate
targeting critical limb ischemia, are perceived as safer by physicians, payers, and patients. "Physicians in particular like
autologous cell therapies, because if you're starting with the patient's own cells, there's not the risk of [immune] rejection
and there's not the perceived or real safety issues that people have with allogeneic cells," says Mayleben. However, Mayleben
concedes that in some ways, working with allogeneic cells is "easier" due to manufacturers not having to process cells for
each individual seeking treatment.
At Stem Cells Inc., which is focused on CNS disorders using cells derived from fetal brain tissue—which are classified as
"adult" stem cells as opposed to hESC, since organs have fully formed—there is less of a tumorigenicity risk to patients,
a key challenge with embryonic stem cells. Being close to "totipotent," or capable of turning into any cell type in the body,
hESC must be "terminally differentiated" in the lab, ex vivo, a complex process that prevents the cells from turning into
anything other than the cell type or organ tissue that's being targeted in the patient. If just one cell slips through without
being differentiated in the manner, it could lead to tumors. In this example, a patient could end up with tumors containing
cartilage, teeth, hair or bone, for example, a gruesome outcome to clinicians and potential investors. However, stem cell
companies—Stem Cells Inc. included—have largely avoided this problem, primarily by using other kinds of stem cells whose fates
are more hardwired, unlike the youthful and fancy-free embryonic stem cells. Or by meticulously screening embryonic cells
using assays or procedures to assess whether cells have indeed been made to "dance to a tune" that leads to terminal differentiation,
as McGlynn put it.
Stem Cells Inc. is pursuing therapies across a range of CNS disorders including spinal cord injury, stroke, Alzheimer's, lysosomal
storage disorders, cerebral palsy, and macular degeneration, among others. McGlynn says the putative label for his company's
neural stem cells would be as follows: "A neuro-active, cell-based therapeutic, for the restoration and preservation of neurological
function in a broad range of CNS disorders."
We were last in the IVF clinics in 2005, so our methodology doesn’t destroy, harm, or change the fate of the embryo in any
way. —Gary Rabin
Pluristem Therapeutics, an Israeli cell therapy firm that raised roughly $34 million in a September public offering of common
stock, is also targeting patients with critical limb ischemia, the end stage and most severe form of pulmonary artery disease.
In its lead program, Pluristem treated 27 patients —12 in the United States and 15 in Germany—with the goal of demonstrating
progression-free survival against historical data. The result was 85 percent progression-free survival, compared to 65 percent
in the historical, placebo-controlled studies. For CLI, however, it's likely that FDA would require amputation-free survival,
which the endpoint that Aastrom Biosciences is looking at in Phase III. Pluristem is now moving forward with a Phase II trial
evaluating its placental expanded cells (PLX) in the treatment of intermittent claudication, a subset of peripheral artery
disease. Through a compassionate use program in Israel earlier this year, the company also successfully saved the life of
a seven-year-old patient with aplastic bone marrow, who had failed a bone marrow transplant. She was given two doses of PLX
cells one week apart, via intramuscular injection, and "in seven to 10 days, she had recovery of her red cells, white cells,
and platelets, and was discharged" from the hospital, says Bill Prather, Pluristem's senior VP, corporate development. The
company has saved two additional bone marrow patients' lives in the last few months.
Pluristem struck its first PLX out-licensing deal with United Therapeutics in 2011, to fund development for treating pulmonary
arterial hypertension, a chronic syndrome characterized by abnormally high pressure in the arteries leading from the heart
to the lungs. The company manufactures its own cells, which are derived from human placentas, and hopes that its sophisticated
3D culturing process will lead to a situation where "we will be considered by our partner as the best supplier," says CEO
Zami Aberman. "We don't want to give any manufacturing rights to the pharma companies." The subcutaneous administration of
PLX is also a differentiating factor of Pluristem's therapies. "We don't believe we need to go to the intravenous route because
that's a dose-limiting procedure. There's a certain amount of cells you can't exceed because the cells get stuck in your lung,"
says Prather. "In our ischemia trials, it was an outpatient procedure...it took about 20 minutes [to administer the cells]."
Pluristem's PLX cells cannot be differentiated, and the company isn't focused on pluripotent cells, or cells that can be differentiated
in the lab. Instead, Pluristem is focused on cells that are "good secretors, that can secrete a variety of factors, which
is a completely different approach than embryonic stem cell therapies." The company is "working with both the EMA and the
FDA on all our projects," says Prather. By forming relationships with expectant mothers, Pluristem is able to show up for
scheduled C-sections to collect the placenta. "We'll be able to manufacture 10,000 doses at a dose of 300 million cells from
one placenta, and we have a lot of them,"according to Prather.