Pluristem Therapeutics Inc., an Israeli regenerative medicine company, said several of the seven COVID-19 patients treated with its allogeneic placental expanded (PLX) cells have progressed from suffering severe symptoms of the disease to signs of clinical recovery, including respiratory improvements. Encouraged by the experiment, carried out a under compassionate use program, the company next plans to apply for permission to run a multinational trial of PLX cells to treat people suffering from complications associated with the pandemic. Company shares (NASDAQ:PSTI), which rose 50% by midday, closed April 7 at $4.11, up 22%.
Investigators collaborating with the company have dosed seven COVID-19 patients each with a single 300-million-cell-dose of PLX-PAD, an allogeneic mesenchymal-like cell therapy the company was already studying in two phase III trials, one for the treatment of critical limb ischemia and another for muscle regeneration following hip fracture.
"We have a lot of evidence that a good portion of the mechanism of action is the anti-inflammatory and immunomodulatory capability of the cells," Pluristem CEO and President Yaky Yanay told BioWorld. "It seems to be like a perfect fit. We are very confident in the safety profile of the product," he said.
Six of the patients, which Yanay said were in "extremely severe" condition before dosing with PLX-PAD, have completed at least seven days of follow-up with a seventh headed toward that milestone following treatment on April 5. In each, progression in the disease appeared to change after two to three days, he said.
Of the six evaluable at one week post-treatment, four have demonstrated improvement in respiratory parameters and three are in advanced stages of weaning from ventilators. Two patients with multiple-organ failure prior to treatment showed clinical recovery in addition to the respiratory improvement.
One patient has shown no change in respiratory parameters and is still breathing with the assistance of a ventilator and remains relatively stable, the company reported, while another has shown deterioration in respiratory parameters.
Now, with the first patient enrolled in a second group of compassionate use cases Pluristem's team will track, it plans to enroll yet more patients in the early testing, something that has been helped by support from the Israeli Ministry of Health, the FDA's efforts to quickly turn around compassionate use patient requests and support from Pluristem's partner in the work at the BIH Center for Regenerative Therapy and the Berlin Center for Advanced Therapies at Charite University of Medicine Berlin.
"The goal now is to move as quickly and efficiently as we can to full-blown clinical studies," Yanay said, something that will be helped by Pluristem's substantial GMP manufacturing capacity in Israel and pre-existing inventory of cells. Though the design for the study hasn't been finalized yet, work to define the protocols for a multinational controlled study are at an advanced stage. The multi-arm study is likely to test multiple dose levels of PLX-PAD against standard-of-care treatment in COVID-19 patients on ventilation with ARDS, with the goal of reducing ventilation days and mortality rates.
A broad effort
Pluristem's work fits into a growing wave of efforts by companies in the regenerative medicine community racing to find both a vaccine for SARS-CoV-2 and meaningful therapeutics for COVID-19. Between Pluristem's announcement and the recent receipt of FDA approval by Perth, Australia-based Mesoblast Ltd. to test its allogeneic mesenchymal stem cell product candidate in patients with ARDS caused by COVID-19, Tuesday represented important progress for ongoing efforts.
Athersys Inc., Celltex Therapeutics Corp. and Wuhan Hamilton Biotechnology Co. Ltd. are also working on cell therapy products to address respiratory issues. (See Biopharma products in development for COVID-19.)
"Obviously, if you can have some positive effect on [ARDS], even though you're not curing the disease, you can in theory keep the patient off a ventilator, which would be a really big deal," Michael Lehmicke, director of Science & Industry Affairs at the Alliance for Regenerative Medicine, told BioWorld.
In response to the current situation and the dramatic need for therapies for COVID-19 and funding opportunities that have emerged in The Coronavirus Aid, Relief and Economic Security Act, companies "may try to pivot a bit and develop therapies that are more targeted to infectious disease," he said.
Such support, especially in provisions targeted at funding new research through the NIH and BARDA, could prove especially important to regenerative medicines companies, depending on their ambitions. Though the subset of patients with ARDS is relatively small, "if you're trying to treat COVID-19 as opposed to ARDS that results from COVID-19, that's a whole other story. I would say that would be a significant challenge," he said.
Further details of the regenerative medicine sector's response to COVID-19 will likely take at least a couple more months to come into better focus. Meanwhile, Lehmicke said he's keeping an eye on whether companies in the long term pivot toward tackling other emergent diseases without innate immunity, an area to which knowledge of immunology and the technical capabilities that have developed alongside it could be repurposed and deployed.