One company working towards an ARDS treatment is Athersys, a biotech company focusing on regenerative medicine therapies for diseases with significant unmet need.
“ARDS makes you feel like you can’t breathe, like you’re suffocating,” said Eileen Rubin, J.D., ARDS survivor and Founder of the ARDS Foundation.
Acute respiratory distress syndrome (ARDS) is as scary as it sounds. A person is usually sick with something else, such as the flu, COVID-19, or sepsis (a serious bloodstream bacterial infection), before they develop ARDS. Suddenly, the person has trouble breathing, is short of breath, and feels like they are suffocating. ARDS patients quickly go into respiratory distress and usually need to be put on a ventilator (and are typically put into a medically induced coma) to get them the oxygen they so desperately need.
“Within about two days in the hospital, I went into respiratory arrest and was diagnosed with ARDS at age 33,” Rubin explained. “I spent nine weeks in the hospital, eight weeks on a ventilator, and four weeks in a medically induced coma.”
Despite the seriousness of ARDS, Rubin wants those affected by the disease and their families to know there is hope. Over 50% of the almost 200,000 Americans diagnosed with ARDS each year recover and it is not a terminal illness.
“ARDS patients are given the grim statistics about what is going to happen to them and how dire it is,” she added. “Where there is life, there is hope – families should talk to their ARDS loved one if they’re in a coma, tell them the reasons they need to have hope and focus on the things they need to survive for.”
This year, more people will be diagnosed with ARDS due to COVID-19. ARDS tends to develop in severely ill COVID-19 patients and is a common cause of death in these critical patients.
Rubin told BioSpace how her ARDS experience prompted her to help others by creating the ARDS Foundation. We also spoke to Gil Van Bokkelen, Ph.D., CEO of Athersys, a company developing stem cell therapy to treat ARDS, which is currently being tested in COVID-19 patients who develop ARDS.
Excitingly, the FDA recently designated Athersys’ stem cell therapy (MultiStem®) as a Regenerative Medicine Advanced Therapy (RMAT) for ARDS. This allows the company to work closely with the FDA and receive guidance on product development to enable an efficient product approval process. MultiStem also received Fast Track designation for ARDS from the FDA in May 2019.
Eileen Rubin, J.D., ARDS survivor and founder of the ARDS Foundation (left) and Gil Van Bokkelen, Ph.D., Chairman and CEO of Athersys (right). Source: Eileen Rubin and Athersys.
Eileen’s story: “I can’t breathe. I think I’m dying.”
It all started with lower back pain – not something you think would land you in the hospital on a ventilator, fighting for your life days later.
“I was suffering from excruciating lower back pain for eight days before going to my doctor,” Rubin explained. “They said I likely pulled a muscle, prescribed me a muscle relaxant, and sent me home.”
A week later, she still felt horrible and was having difficulty breathing. She saw another doctor, who basically said the same thing and didn’t order any tests, sending her home with the same muscle relaxer.
The next morning, she awoke around 5:00 a.m. with labored breathing and difficulty walking. After calling her doctor, they said they wouldn’t see her again because they had just seen her yesterday. Frustrated and scared, she found another doctor who saw her later that afternoon. By then, her blood pressure was dangerously low (70/50), she had blood in her urine and she became delirious. This third doctor finally ordered bloodwork and a chest x-ray but sent her home to await the results.
She awoke very early the next morning to a phone call from the doctor telling her to go to the emergency room immediately – her white blood cell count was 3.5 times higher than normal. Once in the emergency room, she saw a pulmonologist who said she would need to be ventilated if her breathing got any worse. That night, her kidneys failed. Luckily, she was stabilized, but during her second day in the hospital, she became extremely short of breath.
“I said to my mother, ‘I can’t breathe. I think I’m dying.’ And my mother ran out of the room,” Rubin recounted. “My mother rushed to find my internist and repeated what I had said. My internist said, ‘She’s okay, I just saw her. She’s just anxious.’ My mother replied, ‘Listen, she just said this, and I need you to come see her now.’ So, the doctor came in and saw me.”
Upon realizing how badly Rubin was doing, her doctor cleared the room, called a code and declared that she was in respiratory arrest. Almost three hours later, her family was let back into her room, only to find her ventilated in a medically induced coma.
Unfortunately, this pain denial isn’t uncommon – pain that women experience is far too often downplayed, not taken seriously, or outright dismissed in healthcare.
“A woman in her 30s says she has pain in her chest and is having difficulty breathing is seen totally differently than a man with the same symptoms,” Rubin noted. “My doctors didn’t even consider doing an EKG.”
After receiving many units of blood, having her lungs collapse multiple times, developing some hospital-acquired infections and having five chest tubes placed, she was sent home to slowly recover after nine weeks in the hospital. Read her entire battle with ARDS, “From Trial Attorney to Life Support in Only Days…,” on the ARDS Foundation website.
ARDS Foundation
A few years after recovering from her battle with ARDS, Rubin wanted to help other ARDS patients and their families, providing the information and support that she and her family didn’t have.
“When my sister went on the internet, all she got were medical articles filled with jargon and autopsy photos,” Rubin commented. “There was nothing positive written about ARDS, nothing that offered any support.”
Rubin wanted to change that, so she created the ARDS Foundation in 2000. The foundation initially started to create a simple, easy to understand brochure for families explaining what ARDS is. Today, it is a nonprofit organization offering support, information, and awareness of ARDS to patients and families.
“After ARDS, a lot of people become less outgoing, more reserved,” Rubin noted. “They don’t feel like doing certain things and their personality changes – they may suffer from anxiety, depression, or PTSD because their life is completely altered.”
The foundation is also facilitating medical research to improve ARDS care and treatment.
“My ARDS was treated much like it is today, with supportive therapy and ventilation – there is no specific treatment for ARDS,” Rubin explained. “My doctors were just trying to put out all the fires that were going on while I was critically ill.”
A stem cell therapy for ARDS
One company working towards an ARDS treatment is Athersys, a biotech company focusing on regenerative medicine therapies for diseases with significant unmet need. Their product, called MultiStem®, is a certain type of off-the-shelf human stem cell being studied to treat a wide array of conditions, including neurological, cardiovascular, inflammatory, and immune diseases.
A vial of MultiStem® cells. Source: Athersys
To make this therapy, stem cells are isolated from the bone marrow of healthy donors and separated to collect a certain population of cells called multipotent adult progenitor cells (MAPC). These specific stem cells are expanded in the lab to become MultiStem; they can be frozen for extended periods of time, ready for use when a patient needs them.
“These cells have a robust and highly distinctive expansion potential – material from a single donor can be used to produce millions of doses, which is well beyond the limits of other donor-derived cell types,” explained Van Bokkelen.
MultiStem cells don’t express molecules that would elicit a rejection response, meaning they don’t require donor-recipient matching or immune suppression when being given to the patient. “The cells can be used like a universal donor Type O blood product,” Van Bokkelen added.
Because of the time sensitive nature of the conditions MultiStem is being used to treat (ARDS, stroke, trauma), timing is everything; being able to simply thaw ready-to-use cells and administer them to the recipient rapidly is key. Once the cells are delivered into the patient, they express a range of proteins and immune factors, giving the cells a unique ‘drug-like profile.’
“We’re administering living cells that are dynamically responsive to the signals and cues produced by the human body, unlike traditional pharmaceuticals or biologics that are designed to do one very specific thing,” said Van Bokkelen. “MultiStem is a living multifactor delivery system – the cells home to sites of tissue damage and inflammation where they perform a whole series of actions.”
When a virus like COVID-19 or another pathogen enters the body, the immune system becomes activated to destroy the pathogen. Sometimes, a hyperactive, over inflammatory state is triggered, which can actually be counterproductive and harmful. In fact, this “cytokine storm” is thought to cause ARDS in severe COVID-19 patients, resulting in the need for ventilation and frequently leading to death among seriously and critically ill individuals.
“If we administer MultiStem cells to patients in this hyperinflammatory state, the cells will home to the spleen, the warehouse of activated immune cells, and calm everything down, restoring immunological homeostasis,” Van Bokkelen explained. “MultiStem cells don’t just regulate one type of cell, they regulate a whole series of pathways – that is what makes them so powerful.”
Once the overactive immune response has been reigned in, the body is able to recover and heal faster, rather than spiraling out of control.
You might be thinking, “If we have these stem cells inside us already, why wouldn’t they do the same thing and tamp down the overactive immune response in the first place?” While a person in the throws of a hyperactive immune response may have some of these specific stem cells (usually there is a very small amount in the bone marrow), they are slow to mobilize and there may not be enough to balance out the ‘storm’ of activated immune cells.
“If someone sustains a serious injury and they’re losing lots of blood, we give those patients a blood transfusion,” Van Bokkelen posed. “It’s not that the body can’t make red blood cells, it’s just that it can’t do it fast enough to deal with the rapid blood loss. Similarly, we can administer MultiStem to a patient much faster than the body would be able to respond on its own, helping to get things back to where we want them to be.”
A similar situation happens during a hyperactive immune response – administering MultiStem to provide the body with more calming stem cells helps balance the immune response quickly to avoid damage to the patient.
Another bonus of these cells is that they have a finite half-life in the body; unlike a bone marrow transplant that replaces the bone marrow permanently, MultiStem cells are cleared over time just like other normal cells in the body.
MultiStem cells to treat COVID-19-induced ARDS
When COVID-19 appeared, the Athersys team thought MultiStem may be helpful for ARDS in COVID-19 patients because it had already been tested in ARDS animal models and clinical studies. Previously, MultiStem, delivered either intravenously or directly to the lungs (endobronchially), effectively treated ARDS in sheep alone and in conjunction with extracorporeal membrane oxygen (ECMO).
Athersys concluded a randomized, double-blind, placebo-controlled Phase I/II study (MUST-ARDS) last year in 36 ARDS patients. Patients treated with MultiStem had:
- More ventilator-free days (12.9 days vs. 9.2 days for the placebo-treated group)
- More ICU-free days (10.3 days vs. 8.1 days in the placebo group)
- A lower mortality rate (25 percent vs. 40 percent in the placebo group)
- Improved quality of life 1-year after treatment compared to the placebo group, with even larger clinical benefits among the more seriously ill
Overall, the cells were well-tolerated with no serious adverse reactions within 24 hours of administration.
“We saw a dramatic difference one year after patients received a single dose of MultiStem,” Van Bokkelen said. “We were really helping patients get on the path to recovery and get back to where they wanted to be in terms of functional independence and quality of life.”
The company currently has two ongoing studies of MultiStem in ARDS patients: ONE-BRIDGE, a Phase II study in non-infection induced (pneumonitis) ARDS patients; and MACoVIA, a Fast Track designated Phase 2/3 study in COVID-19 induced ARDS patients.
ONE-BRIDGE, sponsored by HEALIOS K.K., is a randomized study aiming to enroll 35 adult participants to assess MultiStem’s safety and effects on ventilator-free days and various biomarkers. Enrollment is expected to be completed by the end of 2020.
MACoVIA is a randomized, placebo-controlled study designed to enroll up to approximately 400 adult participants to assess MultiStem’s safety and tolerability in COVID-19 ARDS patients, as well as evaluate its effect on ventilator-free days and all-cause mortality. “We worked with the FDA to get study approval in an accelerated timeframe of a few months – we started enrolling patients in early May,” added Van Bokkelen. “We’re hoping to complete the study sometime next year.”
“We welcome the progress being made by Athersys to find a solution to the huge unmet need of ARDS treatment,” Rubin commented. “We hope that their Phase 3 trials are completely successful because this treatment is much needed. We support all companies engaging in research on treatment options for ARDS.”
