Ampion and Inflammatory Joint Disease
Osteoarthritis is the most common form of arthritis affecting over 100 million people in the United States. While osteoarthritis can strike any joint, osteoarthritis of the knee (OAK) is the most prevalent, affecting over 15 million people in the United States and over 200 million people worldwide. It is estimated that approximately 45% of people will develop OAK in their lifetime. The global osteoarthritis therapeutics market continues to expand and is expected to exceed $10 billion by 2027. Despite the obvious need for effective therapies for osteoarthritis, few adequate treatments currently exist for this chronic, debilitating disease.
Osteoarthritis is an incurable and progressive disorder of the joint involving the degradation of cartilage, ligaments, and bone caused by inflammation of the soft tissue and bony structures. The condition worsens over time and leads to progressive thinning of articular cartilage, narrowing of the joint space, synovial membrane inflammation, and osteophyte formation. Symptoms include aching, burning and sharp pain along with decreased range of motion and function. Once a patient has OAK, there is no cure, and the disease will eventually progress to the most severe form of OAK, further increasing pain and reducing functional capability. Progression of OAK leaves patients with little or no treatment options, and the FDA has recognized that severe OAK is an “unmet medical need” with no existing licensed therapy available.
The pain and functional disabilities in OAK are attributed to immune-mediated inflammation which causes long-term, chronic joint synovitis. An overabundance of inflammatory proteins (TNFα, IL-1β, IL-6, IL-12) in the joint continue to signal inflammation, which causes further tissue damage and interrupts natural chondrocyte metabolism and cartilage maintenance. A cycle of inflammation is observed where continued cartilage destruction overwhelms the biological signaling required for tissue repair and healing, ultimately causing the knee joint to transform into a painful, diseased state. Therapeutic targets in the immune system responsible for this cycle of inflammation provide a basis for treating OAK as well as OA in other joints (hip, shoulder, hand), and have the potential for modifying or reversing the disease.
About Ampion and Osteoarthritis
Ampion is being developed as an intra-articular injection to treat the signs and symptoms of severe OAK, which continues to be a growing epidemic in the United States and other countries worldwide.
Ampion regulates key components of the immune response connected to pain, inflammation, and joint damage in osteoarthritis. In vitro studies show that Ampion reduces the production of the cytokines responsible for inflammation (TNFα, IL-1β, IL-6, IL-12) 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 has an overall clinical effect that has been shown to relieve pain and improve function in the knee for patients in clinical trials. Additionally, this mechanism may have the potential to stop, or reverse, disease progression after continued treatment with Ampion, which needs to be evaluated in the clinical.
Clinical Status of Ampion in OAK
Clinical trials for Ampion treatment of OAK are advancing through late-stage clinical trials in the United States. Clinical data shows consistent safety and efficacy for severely diseased OAK patients after a single injection of Ampion. The second Phase III trial in OAK was paused early 2020 due to the COVID-19 pandemic. Ampio has recently proposed to the FDA to close that study and use the data gathered in both Phase III trials to support a commercial Biologics Licensing Application (“BLA”).
The first Phase III trial was recognized by the FDA to be an adequate and well-controlled study providing evidence of clinical efficacy and serves as one of two pivotal trials to support the marketing application. The study (AP-003-A) was a randomized, placebo-controlled trial of patients with OAK who received a single intra-articular injection of Ampion or saline control. The results showed a statistically significant reduction in pain in patients treated with Ampion compared to those given the saline injection. Patients who received Ampion also showed a significant improvement in knee function compared to patients who received saline. Treatment with Ampion was safe and well-tolerated with fewer adverse events than the saline control group.
The second Phase III pivotal trial to support efficacy for the Ampion marketing application is being conducted currently under an FDA Special Protocol Assessment (SPA). This trial was paused in early 2020 due to the pandemic. The FDA provided guidance in December, 2020, that would allow Ampio to complete the study using the data collected thus far.
In March, 2021, Ampio submitted a proposal to the FDA to use existing data only in submitting its application for a commercial BLA for Ampion intra-articular injection in OAK. A factor supporting this proposal was the large block of historic data from previous clinical trials. This represents a large base of knowledge on patients with severe OAK, one that does not exist outside of Ampio. The inclusion/exclusion criteria was practically identical in all of Ampio’s single intra-articular injection trials, with similar demographics including patient age, weight, severity, and dose, and all patients were evaluated at 12 weeks.
The current study remains blinded until Ampio receives written confirmation from the FDA that the proposal to use only existing data has been accepted and the existing SPA remains in effect.
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.