Ampion and Inflammatory Lung Diseases, COVID-19

About COVID-19

The United States and the rest of the world are experiencing a public health crisis due to the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) also known as coronavirus disease of 2019 (COVID-19). Infection and death rates continue to spike, with patients experiencing respiratory complications and requiring hospitalization as the virus sets off a vicious cycle of inflammation, also known as the cytokine storm.

Initial symptoms of COVID-19 infection include fever, cough and shortness of breath. Once infected, the virus moves down a patient’s respiratory tract, where the lungs may become inflamed, making it difficult to breathe. In some cases, the disease progresses to severe illness with patients struggling to breathe, resulting in low blood oxygen levels and requiring oxygen therapy, intensive care, and ventilation. These patients develop critical respiratory complications like acute respiratory distress syndrome (ARDS) and acute lung injury (ALI).

Treatment options for COVID-19 are limited and the numbers of infection continue to rise. Once a patient has respiratory complications like ALI and ARDS, the mortality rate is estimated to be 40%. Respiratory disease, like ALI and ARDS, are characterized by widespread inflammation in the lungs. The triggering insult to the lung has been associated with a hyper innate inflammatory response, or cytokine storm, where cytokines and related proteins (e.g., TNFα) are excessively increased. This hyperactive inflammatory response results in pulmonary edema and fibrosis with poor prognosis. Therapies which can target the inflammatory response may improve the clinical outlook for these patients.

Ampion and COVID-19

As an immunomodulatory agent with anti-inflammatory effects, Ampion interrupts the hyperactive immune response associated with COVID-19 and may improve the clinical outcome for patients suffering from its complications. Ampion is being investigated as a therapy for patients with COVID-19 by inhalation to treat localized inflammation in the lungs and by intravenous (IV) infusion to address the systemic inflammation in the lungs, heart, and kidney observed with COVID-19 infection.

Ampion regulates key components of the immune response connected to pulmonary edema, inflammation, and lung damage in respiratory illness. In vitro studies show that Ampion reduces the production of the cytokines responsible for inflammation (TNFα, IL-1β, IL-6) by regulating with the genetic transcriptional pathways (NFκB, STAT) responsible for the overproduction of these cytokines while activating anti-inflammatory proteins responsible for tissue growth and healing. This mechanism of action may have a clinical effect by interrupting the pulmonary disease, attenuating the cytokine storm, and improving the clinical outcome in patients with COVID-19, as studied in the Ampion COVID-19 clinical program.

Clinical Status of Ampion and COVID-19 – Intravenous (IV) Ampion

Administering Ampion by IV has the potential to treat systemic complications of COVID-19 infection, such as inflammation in the heart and kidneys.

In September 2020, Ampio announced positive results in a Phase I trial for IV Ampion treatment for COVID-19 patients requiring oxygen. The study met its primary endpoint for the safety and tolerability of IV Ampion treatment.

At hospital discharge, the IV Ampion treatment group had a stronger clinical improvement than the COVID standard of care control group, as determined by both the World Health Organization (WHO) clinical improvement scale and the National Early Warning Score 2 (NEWS2), which is recommended by the National Institute for Health and Care Excellence (NICE) in its guidelines for the management of COVID-19 patients in critical care.

The trial (AP-016) was a randomized, controlled study of adults hospitalized with COVID-19 receiving supplemental oxygen. Patients were randomized 1:1 (active vs control) to receive standard of care (SOC) for COVID-19 plus IV Ampion treatment or SOC alone. Standard of care included the use of anti-viral therapies such as Remdesivir or convalescent plasma. The majority of the patients in the control group were prescribed Remdesivir while no patients in the IV Ampion group received that anti-viral therapy.

Administering Ampion through IV has the potential to treat systemic complications of COVID-19 infection, such as inflammation in the cardiovascular system and kidney.

An international study has since been initiated in Israel and the U.S. with the focus on patient safety and efficacy, as measured by improvement in the clinical course of the disease and related outcomes for patients with moderate to severe COVID-19. Ampion IV treatment targets systemic inflammation in the body of patients with moderate to severe COVID-19 symptoms. In addition, this study will assess the effect of Ampion IV treatment in both a hospital setting and as a therapy for out-patient care.

Recent feedback from the FDA recommended that this trial move to become a Phase II double-blind, placebo-controlled trial, similar to one in inhaled Ampion.

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Clinical Status of Ampion and COVID-19 – Inhaled Ampion (Nebulizer)

Administering Ampion to patients by inhalation allows the drug to directly target and attenuate inflammation in the lungs.

In October 2020, Ampio began a Phase I clinical trial to study the effects of inhaled Ampion in patients with respiratory distress due to COVID-19 infection. Ampion is delivered by a nebulizer with a hand-held device for inhalation by patients with less severe cases of respiratory illness, and with non-invasive ventilation (face mask) and mechanical ventilation (intubation) devices to those patients with severe cases.

Directly administering Ampion to patients by inhalation allows the drug to directly target and attenuate inflammation in the lungs.

Preliminary results from the AP-014 Phase I trial of inhaled Ampion indicate:

  • Ampion demonstrated an improvement in all-cause mortality in COVID-19 patients compared to standard of care (SOC). A lower all-cause mortality rate of 8% is observed for the Ampion treatment group, compared to 21% in standard of care alone.
  • Patients who received Ampion required less hospitalization time. The average hospital length of stay was 7 days for the Ampion group compared to 11 days for standard of care patients.
  • Patients who received Ampion required less oxygen than standard of care alone, and 86% of Ampion patients were stable or had improvement compared to 75% of SOC patients.
  • More patients who received Ampion were stable or had improvement on a scale of clinical improvement compared to standard of care alone. By day 5, 86% of patients who received Ampion were stable or had improvement compared to 75% of standard of care patients. This trend in improvement with Ampion treatment is noted as early as day 2 and continues to day 5.
  • Adverse events were the same between Ampion and standard of care, and no drug-related serious adverse events have been reported.

This data was presented to the FDA for consideration as a potential emergency use authorization treatment for COVID-19 patients, and the FDA recommended moving to a Phase II randomized, double-blind, placebo-controlled clinical trial. The FDA indicated that this trial design may allow for an effective and efficient review of data results and support the safety and statistical significance and effectiveness of Ampion treatment, which are necessary for the FDA to objectively review the known and potential benefits of Ampion against any potential risks to be considered for emergency use authorization.

The protocol of this Phase II clinical trials for inhaled Ampion in treatment of COVID-19 respiratory distress is being finalized, with the trial expected to start in Q2 2021.

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Clinical Status of Ampion and Post-Acute Sequelae of SARS-CoV-2 (PASC) COVID-19 “Long Hauler” Symptoms

Inhaled Ampion may be useful in helping those who still suffer the after-effects of COVID-19 long after the virus is gone.

In March, 2021, Ampio outlined plans for a forthcoming Phase I clinical trial utilizing inhaled Ampion with patients exhibiting “long hauler” COVID-19 symptoms, now known clinically as Post-Acute Sequelae of SARS-CoV-2, or PASC. A significant percentage of the millions of people who have contracted COVID-19 over the past year – even those with mild or asymptomatic cases – continue to suffer effects from the disease long after there is no detectable virus in their system.

The complications from COVID-19 stem not from the virus but from the out-of-control inflammatory immune response it triggers, which remains a problem long after the infection is over. Inhaled Ampion may provide a significant therapeutic benefit for those patients plagued by the “long haul COVID-19 symptoms” of PASC.

The trial design will deal specifically with respiratory distress-related symptoms and will involve an “at home” treatment, where patients will receive a nebulizer and a five-day supply of inhaled Ampion. The trial protocol is being finalized, with commencement of the study expected by mid-Q2 2021.

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Ampion regulates the immune response

Ampion uses the power of the immune response and is in development to treat osteoarthritis, respiratory illness due to COVID-19, and a wide range of other debilitating and life-threatening inflammatory conditions.

Learn About Ampion