Michael Barbella, Managing Editor04.21.21
MiMedx Group Inc.'s studies of its AmnioFix Injectable drug for treating several musculoskeletal conditions is about to enter its final stage.
Patients enrolled in the company's Phase 3 studies for AmnioFix—micronized dehydrated Human Amnion Chorion Membrane (mdHACM)—have completed their last clinical visits; these patients received mdHACM as a potential treatment for plantar fasciitis and achilles tendonitis. In addition, all clinical effectiveness endpoint visits have been completed in a Phase 2B study of mdHACM as a potential treatment for knee osteoarthritis. With the completion of these patient visits, the company will begin reviewing and analyzing the data from all three trials in order to release results in the third quarter this year.
“Completion of the Phase 2B study for mdHACM as a treatment for knee osteoarthritis marks an extraordinary milestone,” said Alfred Gellhorn, M.D., adjunct associate professor of Clinical Rehabilitation and director of Sports Medicine, Weill Cornell Medicine. “There is a tremendous unmet need for safe and effective treatment options for knee osteoarthritis. The osteoarthritis community has long recognized that current treatment options are painfully insufficient. The benefit of a novel therapeutic option in this setting for both patients and clinicians cannot be overstated.”
The Micronized dHACM vs. Saline in the Treatment of Osteoarthritis of the Knee Trial, the first randomized clinical study of mdHACM injection in treating knee osteoarthritis (KOA), is a Phase 2B, prospective, double-blinded, randomized controlled trial of the mdHACM injection as compared to saline placebo injection in the treatment of osteoarthritis of the knee. Trial enrollment was planned to include 466 patients between the ages of 21 to 80 years, with a diagnosis of osteoarthritis defined as grade 1 to 3 on the Kellgren Lawrence grading scale and a Visual Analog Scale (VAS) for Pain score greater than 45. Due to a lower-than-expected number of study participant dropouts, and with an adequate number of patients meeting the required time in study to assess the primary endpoint, the final number randomized will be 447 patients.
The primary efficacy endpoints include change from baseline in VAS at 90 days, change from baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 days, and incidence of related Adverse Events (AEs), Serious Adverse Events (SAEs), and Unanticipated Adverse Events at 365 days. Secondary endpoints include: change from baseline in VAS at 180 days and change from baseline in WOMAC at 180 days. The WOMAC Index has become a standard study metric in KOA studies and its use has been extensively validated.
The blinded efficacy visits for this study are complete, with the 12-month safety visit follow up as requested by U.S. Food and Drug Administration (FDA) scheduled to compete in October 2021. The company intends to initiate a Phase 3 study of mdHACM injection in KOA treatment in Q3 2021, after an end of Phase 2 meeting with FDA, and planning for this effort is underway.
Osteoarthritis (OA) is by far the most common joint disease—millions of adults experience pain and decreased quality of life every day because of joint destruction caused by osteoarthritis. Osteoarthritis is responsible for a staggering public health and economic impact: more than 242 million people worldwide currently suffer from symptomatic OA of the knee and hip; 45 percent of all people have a lifetime risk of developing OA of the knee; and OA is responsible for $71 billion in lost earnings annually in the United States. Although knee replacement is an option for those with advanced knee arthritis, it carries significant risks, and current treatment algorithm, including oral anti-inflammatory medications, cortisone injections, and hyaluronic acid injections, are limited in the amount of relief it can provide. Anti-inflammatories have negative cardiovascular effects and injected steroids cause further joint degeneration.
“These trials play key roles in our late-stage AmnioFix Injectable pipeline, and with last patient visits complete across the three trials, we will now lock the databases, conduct the appropriate statistical analyses, and request meetings with the FDA to review the findings. We anticipate announcing top-line results of all three trials this summer, have commenced planning efforts to initiate our Phase 3 clinical trial for Knee Osteoarthritis, and plan to file a Biologics License Application (BLA) for plantar fasciitis in the first half of 2022," MiMedx CEO Timothy R. Wright said. "Although we do not anticipate pursuing a BLA for achilles tendonitis, we expect to glean valuable safety data for the AmnioFix Injectable product from that trial. On behalf of MiMedx, I would like to express our sincere gratitude to all the patients, families and physicians who participated in these important studies critical to our submissions to FDA for approvals for the therapeutic use of amniotic tissues.”
The Micronized dHACM Injectable for the Treatment of Plantar Fasciitis Trial is a Phase 3, prospective, double-blinded, randomized controlled trial of mdHACM injection as compared to saline placebo injection in the treatment of plantar fasciitis. The trial enrolled 277 patients between the ages of 21 and 79 years, with an investigator-confirmed diagnosis of plantar fasciitis for greater than or equal to one month (30 days) and less than or equal to 18 months. Patients were required to have a Visual Analog Scale (VAS) Pain scale of greater than or equal to 45 mm at randomization and be receiving conservative treatment for greater than or equal to one month (30 days), including any of the following modalities: rest, ice, compression, elevation (RICE); stretching exercises; NSAIDs or orthotics. The primary endpoints are change in VAS for Pain at 90 Days and incidence of related adverse events at 180 days, serious adverse events and unanticipated events during the first 12 months post-injection. Secondary endpoints include self-reported responses to the Foot Function Index – Revised (FFI-R) at 90 days.
This study follows a Phase 2B prospective, single‐blinded, randomized controlled trial of 145 patients, which demonstrated a statistically significant reduction in VAS score for pain and an improvement in Foot Function Index-Revised (FFI-R) score. At the three‐month follow‐up, the mean VAS score was reduced by 76 percent for patients in the treatment group compared with a 45 percent reduction for the Control Group (p<0.0001), and the mean FFI‐R score was reduced by 60 percent for patients in the treatment group, while the control group had mean reduction of 40 percent versus baseline (p=0.0004). Overall, at the three‐month study follow‐up visit, 60 (82.2 percent) patients in the treatment group, and 34 (47.2 percent) patients in the control group reported at least a 50 percent reduction in VAS score from baseline (p<0.0001). These effectiveness results were maintained at the six-month secondary endpoint.
More than 2 million people are treated for plantar fasciitis inflammation in the United States annually. In 10 percent of patients treated with traditional measures, the condition progresses to chronic plantar fasciitis-related pain—recovery from which is lengthy and recurrence of which is very common, with an estimated $284 million annual national economic burden. The current treatment algorithm aims to maintain arch shape, modify foot loading and/or improve shock absorbency of the heel through night splints and orthotics. While these measures may assist in reducing pain associated with plantar fasciitis, they do not address the root cause of the condition, which is thought to be both degenerative and inflammatory.
"These studies are designed to prove the clinical efficacy and safety of AmnioFix Injectable in treating frustrating chronic conditions," said Stuart Miller, M.D., principal investigator, Department of Orthopaedic Surgery, MedStar Union Memorial Hospital, and assistant professor, Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Md. “The prior Phase 2B Plantar Fasciitis study has helped establish the product’s safety profile, and I believe these further studies may demonstrate its effectiveness in battling inflammatory conditions. As a physician committed to advancing patient care, I would welcome having additional treatment options that could potentially address the pain and quality of life issues my patients face on a daily basis.”
The Micronized dHACM Injectable for the Treatment of Achilles Tendonitis Trial is a Phase 3, prospective, double-blinded, randomized controlled trial of mdHACM injection as compared to saline placebo injection in the treatment of achilles tendonitis. The trial enrolled 158 patients between the ages of 21 and 80 years, with an investigator-confirmed diagnosis of plantar fasciitis for greater than or equal to one month (30 days) and less than or equal to 18 months. Patients were required to have a Visual Analog Scale (VAS) Pain scale of greater than or equal to 45 mm at randomization and be receiving conservative treatment for greater than or equal to one month (30 days), including any of the following modalities: rest, ice, compression, elevation (RICE); stretching exercises; NSAIDs or orthotics. The primary endpoints are change in VAS for Pain at 90 Days and incidence of related adverse events at 180 days, serious adverse events and unanticipated events during the first 12 months post-injection. Secondary endpoints include self-reported responses to the Foot Function Index – Revised (FFI-R) at 90 days.
The company does not anticipate pursuing a BLA for Achilles Tendonitis at this time, and plans to review options for this program after assessing the results of the Phase 3 study, including potentially exploring the efficacy of AmnioFix Injectable in a more well-defined subset of patients. The company expects to glean valuable safety data from the trial for the AmnioFix Injectable product, which can be used to supplement the data package for other clinical indications underway and inform future clinical indications under consideration.
Achilles tendonitis is a common condition that can occur at any time, but often results from years of overuse (long distance runners, sprinters) and is not typically related to a specific injury. Achilles tendonitis can result in pain and stiffness along the Achilles tendon; pain along the tendon or back of the heel that worsens with activity; severe pain the day after exercising; thickening of the tendon; bone spurs (insertional tendinitis); and chronic swelling. All may result in limited mobility and, potentially, a rupture or tear in the Achilles tendon. Current treatments include rest, icing, NSAIDs; exercise; orthotics; cortisone injections; and surgery. Moderate to severe post-surgical pain is noted in 20 percent to 30 percent of patients and is the most common complication. In addition, wound infection can occur, which is difficult to treat in this location.
Patients enrolled in the company's Phase 3 studies for AmnioFix—micronized dehydrated Human Amnion Chorion Membrane (mdHACM)—have completed their last clinical visits; these patients received mdHACM as a potential treatment for plantar fasciitis and achilles tendonitis. In addition, all clinical effectiveness endpoint visits have been completed in a Phase 2B study of mdHACM as a potential treatment for knee osteoarthritis. With the completion of these patient visits, the company will begin reviewing and analyzing the data from all three trials in order to release results in the third quarter this year.
“Completion of the Phase 2B study for mdHACM as a treatment for knee osteoarthritis marks an extraordinary milestone,” said Alfred Gellhorn, M.D., adjunct associate professor of Clinical Rehabilitation and director of Sports Medicine, Weill Cornell Medicine. “There is a tremendous unmet need for safe and effective treatment options for knee osteoarthritis. The osteoarthritis community has long recognized that current treatment options are painfully insufficient. The benefit of a novel therapeutic option in this setting for both patients and clinicians cannot be overstated.”
The Micronized dHACM vs. Saline in the Treatment of Osteoarthritis of the Knee Trial, the first randomized clinical study of mdHACM injection in treating knee osteoarthritis (KOA), is a Phase 2B, prospective, double-blinded, randomized controlled trial of the mdHACM injection as compared to saline placebo injection in the treatment of osteoarthritis of the knee. Trial enrollment was planned to include 466 patients between the ages of 21 to 80 years, with a diagnosis of osteoarthritis defined as grade 1 to 3 on the Kellgren Lawrence grading scale and a Visual Analog Scale (VAS) for Pain score greater than 45. Due to a lower-than-expected number of study participant dropouts, and with an adequate number of patients meeting the required time in study to assess the primary endpoint, the final number randomized will be 447 patients.
The primary efficacy endpoints include change from baseline in VAS at 90 days, change from baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 days, and incidence of related Adverse Events (AEs), Serious Adverse Events (SAEs), and Unanticipated Adverse Events at 365 days. Secondary endpoints include: change from baseline in VAS at 180 days and change from baseline in WOMAC at 180 days. The WOMAC Index has become a standard study metric in KOA studies and its use has been extensively validated.
The blinded efficacy visits for this study are complete, with the 12-month safety visit follow up as requested by U.S. Food and Drug Administration (FDA) scheduled to compete in October 2021. The company intends to initiate a Phase 3 study of mdHACM injection in KOA treatment in Q3 2021, after an end of Phase 2 meeting with FDA, and planning for this effort is underway.
Osteoarthritis (OA) is by far the most common joint disease—millions of adults experience pain and decreased quality of life every day because of joint destruction caused by osteoarthritis. Osteoarthritis is responsible for a staggering public health and economic impact: more than 242 million people worldwide currently suffer from symptomatic OA of the knee and hip; 45 percent of all people have a lifetime risk of developing OA of the knee; and OA is responsible for $71 billion in lost earnings annually in the United States. Although knee replacement is an option for those with advanced knee arthritis, it carries significant risks, and current treatment algorithm, including oral anti-inflammatory medications, cortisone injections, and hyaluronic acid injections, are limited in the amount of relief it can provide. Anti-inflammatories have negative cardiovascular effects and injected steroids cause further joint degeneration.
“These trials play key roles in our late-stage AmnioFix Injectable pipeline, and with last patient visits complete across the three trials, we will now lock the databases, conduct the appropriate statistical analyses, and request meetings with the FDA to review the findings. We anticipate announcing top-line results of all three trials this summer, have commenced planning efforts to initiate our Phase 3 clinical trial for Knee Osteoarthritis, and plan to file a Biologics License Application (BLA) for plantar fasciitis in the first half of 2022," MiMedx CEO Timothy R. Wright said. "Although we do not anticipate pursuing a BLA for achilles tendonitis, we expect to glean valuable safety data for the AmnioFix Injectable product from that trial. On behalf of MiMedx, I would like to express our sincere gratitude to all the patients, families and physicians who participated in these important studies critical to our submissions to FDA for approvals for the therapeutic use of amniotic tissues.”
The Micronized dHACM Injectable for the Treatment of Plantar Fasciitis Trial is a Phase 3, prospective, double-blinded, randomized controlled trial of mdHACM injection as compared to saline placebo injection in the treatment of plantar fasciitis. The trial enrolled 277 patients between the ages of 21 and 79 years, with an investigator-confirmed diagnosis of plantar fasciitis for greater than or equal to one month (30 days) and less than or equal to 18 months. Patients were required to have a Visual Analog Scale (VAS) Pain scale of greater than or equal to 45 mm at randomization and be receiving conservative treatment for greater than or equal to one month (30 days), including any of the following modalities: rest, ice, compression, elevation (RICE); stretching exercises; NSAIDs or orthotics. The primary endpoints are change in VAS for Pain at 90 Days and incidence of related adverse events at 180 days, serious adverse events and unanticipated events during the first 12 months post-injection. Secondary endpoints include self-reported responses to the Foot Function Index – Revised (FFI-R) at 90 days.
This study follows a Phase 2B prospective, single‐blinded, randomized controlled trial of 145 patients, which demonstrated a statistically significant reduction in VAS score for pain and an improvement in Foot Function Index-Revised (FFI-R) score. At the three‐month follow‐up, the mean VAS score was reduced by 76 percent for patients in the treatment group compared with a 45 percent reduction for the Control Group (p<0.0001), and the mean FFI‐R score was reduced by 60 percent for patients in the treatment group, while the control group had mean reduction of 40 percent versus baseline (p=0.0004). Overall, at the three‐month study follow‐up visit, 60 (82.2 percent) patients in the treatment group, and 34 (47.2 percent) patients in the control group reported at least a 50 percent reduction in VAS score from baseline (p<0.0001). These effectiveness results were maintained at the six-month secondary endpoint.
More than 2 million people are treated for plantar fasciitis inflammation in the United States annually. In 10 percent of patients treated with traditional measures, the condition progresses to chronic plantar fasciitis-related pain—recovery from which is lengthy and recurrence of which is very common, with an estimated $284 million annual national economic burden. The current treatment algorithm aims to maintain arch shape, modify foot loading and/or improve shock absorbency of the heel through night splints and orthotics. While these measures may assist in reducing pain associated with plantar fasciitis, they do not address the root cause of the condition, which is thought to be both degenerative and inflammatory.
"These studies are designed to prove the clinical efficacy and safety of AmnioFix Injectable in treating frustrating chronic conditions," said Stuart Miller, M.D., principal investigator, Department of Orthopaedic Surgery, MedStar Union Memorial Hospital, and assistant professor, Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Md. “The prior Phase 2B Plantar Fasciitis study has helped establish the product’s safety profile, and I believe these further studies may demonstrate its effectiveness in battling inflammatory conditions. As a physician committed to advancing patient care, I would welcome having additional treatment options that could potentially address the pain and quality of life issues my patients face on a daily basis.”
The Micronized dHACM Injectable for the Treatment of Achilles Tendonitis Trial is a Phase 3, prospective, double-blinded, randomized controlled trial of mdHACM injection as compared to saline placebo injection in the treatment of achilles tendonitis. The trial enrolled 158 patients between the ages of 21 and 80 years, with an investigator-confirmed diagnosis of plantar fasciitis for greater than or equal to one month (30 days) and less than or equal to 18 months. Patients were required to have a Visual Analog Scale (VAS) Pain scale of greater than or equal to 45 mm at randomization and be receiving conservative treatment for greater than or equal to one month (30 days), including any of the following modalities: rest, ice, compression, elevation (RICE); stretching exercises; NSAIDs or orthotics. The primary endpoints are change in VAS for Pain at 90 Days and incidence of related adverse events at 180 days, serious adverse events and unanticipated events during the first 12 months post-injection. Secondary endpoints include self-reported responses to the Foot Function Index – Revised (FFI-R) at 90 days.
The company does not anticipate pursuing a BLA for Achilles Tendonitis at this time, and plans to review options for this program after assessing the results of the Phase 3 study, including potentially exploring the efficacy of AmnioFix Injectable in a more well-defined subset of patients. The company expects to glean valuable safety data from the trial for the AmnioFix Injectable product, which can be used to supplement the data package for other clinical indications underway and inform future clinical indications under consideration.
Achilles tendonitis is a common condition that can occur at any time, but often results from years of overuse (long distance runners, sprinters) and is not typically related to a specific injury. Achilles tendonitis can result in pain and stiffness along the Achilles tendon; pain along the tendon or back of the heel that worsens with activity; severe pain the day after exercising; thickening of the tendon; bone spurs (insertional tendinitis); and chronic swelling. All may result in limited mobility and, potentially, a rupture or tear in the Achilles tendon. Current treatments include rest, icing, NSAIDs; exercise; orthotics; cortisone injections; and surgery. Moderate to severe post-surgical pain is noted in 20 percent to 30 percent of patients and is the most common complication. In addition, wound infection can occur, which is difficult to treat in this location.