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VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.
Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.
Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
PTP-001 (MOTYS)
Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.
Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.
Although the changes were only numerically and not statistically different from placebo (n = 71) when looking at the total study population, Ms. Pavesio noted that a key objective of the trial had been to identify populations of patients that may benefit.
When they looked at the effects of PTP-001 solely in those with unilateral knee OA, WOMAC pain scores were decreased to a significantly greater extent with both the high and low doses of PTP-001 vs placebo. Decreases in the least squares mean (LSM) change in WOMAC pain from baseline to week 26 were 26.8 with 100-mg PTP-001, 36.1 with 200-mg PTP-001, and 24.0 with placebo (P = .072). A similarly greater effect for PTP-001 was also seen for LSM change in WOMAC function (26.4, 36.0, and 20.0, respectively; P = .023).
Ms. Pavesio noted that the only real side effect seen during the trial was an initial inflammatory reaction within the first 2 days of IA injection, which resolved within a few days without further problems.
The results are promising enough for Ms. Pavesio and her team to consider a phase 3 trial.
Dr. Lane asked Ms. Pavesio: “So, what’s in the secret sauce? You said it was ground-up placentas?” To which Ms. Pavesio replied that it contained about 300 different molecules which came from amnion, chorion, and umbilical cord tissue obtained from consented placental donation.
Dr. Lane subsequently told this news organization: “It’s probably a bunch of growth factors and cytokines, but if it’s not toxic, and they can standardize it, then it might be good. We remain open minded because we haven’t figured it out.”
Novel Fluticasone Delivery
In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.
Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.
The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.
The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).
These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.
It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.
“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
PPS
Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.
“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”
There are currently two approved formulations: Oral capsules used for the treatment of interstitial cystitis in the European Union, United States, and Australia and an injectable form used in Italy for thromboprophylaxis.
Dr. Ahuja presented data from a phase 2 trial that looked at the effect of once- or twice-weekly subcutaneous injections of PPS vs placebo in 61 people with knee OA pain. Assessments were made after 56, 168, and 365 days of treatment.
Results showed PPS injections resulted in significant improvements in total WOMAC score, WOMAC pain, and WOMAC function, with more PPS- than placebo-treated individuals achieving and then maintaining at least a 30% or greater improvement in pain and a 56% improvement in function.
Rescue medication use was lower in the PPS-treated patients, and Patient Global Impression of Change were significantly higher, Dr. Ahuja said.
Exploratory analyses of synovial fluid biomarkers showed PPS could be having a direct inflammatory effect, with reductions in several proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha.
An assessment of OA disease progression using MRI analysis suggested that there may be an effect on cartilage thickness and volume, as well as bone marrow lesions and overall joint inflammation.
Gene Therapy
Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.
Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.
Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.
However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.
Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (P = .044).
Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.
XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.
The Best Is Yet to Come?
“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.
“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”
Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.
“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
A version of this article appeared on Medscape.com.
VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.
Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.
Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
PTP-001 (MOTYS)
Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.
Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.
Although the changes were only numerically and not statistically different from placebo (n = 71) when looking at the total study population, Ms. Pavesio noted that a key objective of the trial had been to identify populations of patients that may benefit.
When they looked at the effects of PTP-001 solely in those with unilateral knee OA, WOMAC pain scores were decreased to a significantly greater extent with both the high and low doses of PTP-001 vs placebo. Decreases in the least squares mean (LSM) change in WOMAC pain from baseline to week 26 were 26.8 with 100-mg PTP-001, 36.1 with 200-mg PTP-001, and 24.0 with placebo (P = .072). A similarly greater effect for PTP-001 was also seen for LSM change in WOMAC function (26.4, 36.0, and 20.0, respectively; P = .023).
Ms. Pavesio noted that the only real side effect seen during the trial was an initial inflammatory reaction within the first 2 days of IA injection, which resolved within a few days without further problems.
The results are promising enough for Ms. Pavesio and her team to consider a phase 3 trial.
Dr. Lane asked Ms. Pavesio: “So, what’s in the secret sauce? You said it was ground-up placentas?” To which Ms. Pavesio replied that it contained about 300 different molecules which came from amnion, chorion, and umbilical cord tissue obtained from consented placental donation.
Dr. Lane subsequently told this news organization: “It’s probably a bunch of growth factors and cytokines, but if it’s not toxic, and they can standardize it, then it might be good. We remain open minded because we haven’t figured it out.”
Novel Fluticasone Delivery
In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.
Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.
The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.
The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).
These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.
It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.
“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
PPS
Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.
“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”
There are currently two approved formulations: Oral capsules used for the treatment of interstitial cystitis in the European Union, United States, and Australia and an injectable form used in Italy for thromboprophylaxis.
Dr. Ahuja presented data from a phase 2 trial that looked at the effect of once- or twice-weekly subcutaneous injections of PPS vs placebo in 61 people with knee OA pain. Assessments were made after 56, 168, and 365 days of treatment.
Results showed PPS injections resulted in significant improvements in total WOMAC score, WOMAC pain, and WOMAC function, with more PPS- than placebo-treated individuals achieving and then maintaining at least a 30% or greater improvement in pain and a 56% improvement in function.
Rescue medication use was lower in the PPS-treated patients, and Patient Global Impression of Change were significantly higher, Dr. Ahuja said.
Exploratory analyses of synovial fluid biomarkers showed PPS could be having a direct inflammatory effect, with reductions in several proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha.
An assessment of OA disease progression using MRI analysis suggested that there may be an effect on cartilage thickness and volume, as well as bone marrow lesions and overall joint inflammation.
Gene Therapy
Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.
Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.
Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.
However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.
Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (P = .044).
Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.
XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.
The Best Is Yet to Come?
“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.
“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”
Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.
“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
A version of this article appeared on Medscape.com.
VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.
Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.
Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
PTP-001 (MOTYS)
Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.
Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.
Although the changes were only numerically and not statistically different from placebo (n = 71) when looking at the total study population, Ms. Pavesio noted that a key objective of the trial had been to identify populations of patients that may benefit.
When they looked at the effects of PTP-001 solely in those with unilateral knee OA, WOMAC pain scores were decreased to a significantly greater extent with both the high and low doses of PTP-001 vs placebo. Decreases in the least squares mean (LSM) change in WOMAC pain from baseline to week 26 were 26.8 with 100-mg PTP-001, 36.1 with 200-mg PTP-001, and 24.0 with placebo (P = .072). A similarly greater effect for PTP-001 was also seen for LSM change in WOMAC function (26.4, 36.0, and 20.0, respectively; P = .023).
Ms. Pavesio noted that the only real side effect seen during the trial was an initial inflammatory reaction within the first 2 days of IA injection, which resolved within a few days without further problems.
The results are promising enough for Ms. Pavesio and her team to consider a phase 3 trial.
Dr. Lane asked Ms. Pavesio: “So, what’s in the secret sauce? You said it was ground-up placentas?” To which Ms. Pavesio replied that it contained about 300 different molecules which came from amnion, chorion, and umbilical cord tissue obtained from consented placental donation.
Dr. Lane subsequently told this news organization: “It’s probably a bunch of growth factors and cytokines, but if it’s not toxic, and they can standardize it, then it might be good. We remain open minded because we haven’t figured it out.”
Novel Fluticasone Delivery
In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.
Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.
The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.
The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).
These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.
It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.
“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
PPS
Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.
“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”
There are currently two approved formulations: Oral capsules used for the treatment of interstitial cystitis in the European Union, United States, and Australia and an injectable form used in Italy for thromboprophylaxis.
Dr. Ahuja presented data from a phase 2 trial that looked at the effect of once- or twice-weekly subcutaneous injections of PPS vs placebo in 61 people with knee OA pain. Assessments were made after 56, 168, and 365 days of treatment.
Results showed PPS injections resulted in significant improvements in total WOMAC score, WOMAC pain, and WOMAC function, with more PPS- than placebo-treated individuals achieving and then maintaining at least a 30% or greater improvement in pain and a 56% improvement in function.
Rescue medication use was lower in the PPS-treated patients, and Patient Global Impression of Change were significantly higher, Dr. Ahuja said.
Exploratory analyses of synovial fluid biomarkers showed PPS could be having a direct inflammatory effect, with reductions in several proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha.
An assessment of OA disease progression using MRI analysis suggested that there may be an effect on cartilage thickness and volume, as well as bone marrow lesions and overall joint inflammation.
Gene Therapy
Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.
Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.
Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.
However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.
Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (P = .044).
Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.
XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.
The Best Is Yet to Come?
“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.
“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”
Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.
“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
A version of this article appeared on Medscape.com.
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This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were rep</metaDescription> <articlePDF/> <teaserImage>301377</teaserImage> <teaser>Data on several novel injectable drugs were presented at the World Congress on Osteoarthritis, as well as updated data on the gene therapy XT-150.</teaser> <title>Knee Osteoarthritis Trials Show Promising Results for Several Novel Injectables</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>8</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term>26</term> <term canonical="true">21</term> <term>15</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">265</term> <term>290</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240128f8.jpg</altRep> <description role="drol:caption">Alessandra Pavesio</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240128f9.jpg</altRep> <description role="drol:caption">Dr. Mukesh Ahuja</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/240128fa.jpg</altRep> <description role="drol:caption">Dr. Howard Rutman</description> <description role="drol:credit">Sara Freeman/Medscape Medical News</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Knee Osteoarthritis Trials Show Promising Results for Several Novel Injectables</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">VIENNA</span> — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 <span class="Hyperlink"><a href="https://www.medscape.com/viewcollection/37518">World Congress</a></span>.</p> <p>Of all the approaches discussed during the <a href="https://congress.oarsi.org/program/sessions/concurrent-session-09-news-therapies">News in Therapies</a> session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair <a href="https://health.ucdavis.edu/musculoskeletalhealth/bios/lane.html">Nancy E. Lane</a>, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.<br/><br/>Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of <a href="https://reference.medscape.com/drug/elmiron-pentosan-polysulfate-sodium-343348">pentosan polysulfate sodium</a> (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).<br/><br/></p> <h2>PTP-001 (MOTYS)</h2> <p>Indeed, promising results were seen in a <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05100225">phase 2 trial</a> testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. <a href="https://doi.org/10.1016/j.joca.2024.02.076">Results of this dose-finding study</a> were presented by <a href="https://www.bioventus.com/about-us/leadership/alessandra-pavesio/">Alessandra Pavesio</a>, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.</p> <p>Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.[[{"fid":"301377","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Alessandra Pavesio"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>Although the changes were only numerically and not statistically different from placebo (n = 71) when looking at the total study population, Ms. Pavesio noted that a key objective of the trial had been to identify populations of patients that may benefit.<br/><br/>When they looked at the effects of PTP-001 solely in those with unilateral knee OA, WOMAC pain scores were decreased to a significantly greater extent with both the high and low doses of PTP-001 vs placebo. Decreases in the least squares mean (LSM) change in WOMAC pain from baseline to week 26 were 26.8 with 100-mg PTP-001, 36.1 with 200-mg PTP-001, and 24.0 with placebo (<em>P</em> = .072). A similarly greater effect for PTP-001 was also seen for LSM change in WOMAC function (26.4, 36.0, and 20.0, respectively; <em>P</em> = .023).<br/><br/>Ms. Pavesio noted that the only real side effect seen during the trial was an initial inflammatory reaction within the first 2 days of IA injection, which resolved within a few days without further problems.<br/><br/>The results are promising enough for Ms. Pavesio and her team to consider a phase 3 trial.<br/><br/>Dr. Lane asked Ms. Pavesio: “So, what’s in the secret sauce? You said it was ground-up placentas?” To which Ms. Pavesio replied that it contained about 300 different molecules which came from amnion, chorion, and umbilical cord tissue obtained from consented placental donation.<br/><br/>Dr. Lane subsequently told this news organization: “It’s probably a bunch of growth factors and cytokines, but if it’s not toxic, and they can standardize it, then it might be good. We remain open minded because we haven’t figured it out.” <br/><br/></p> <h2>Novel Fluticasone Delivery</h2> <p>In the same session, <a href="https://eupraxiapharma.com/about-us/board-of-directors/person-details/default.aspx?ItemId=ed8f2d4a-2958-490c-b842-cbc74641b5b9">James A. Helliwell</a>, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424001195">presented updated data</a> from the <a href="https://clinicaltrials.gov/study/NCT04120402">SPRINGBOARD phase 2B trial</a> of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.</p> <p>Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.<br/><br/>The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.<br/><br/>The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; <em>P</em> = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; <em>P</em> = .003), function (−2.64 vs −1.99; <em>P</em> = .005), and stiffness (−2.85 vs −2.05; <em>P</em> = .001).<br/><br/>These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.<br/><br/>It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.<br/><br/>“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”<br/><br/></p> <h2>PPS</h2> <p>Although it perhaps can’t be described as a novel injectable per se, <a href="https://theorg.com/org/paradigm-biopharma/org-chart/mukesh-ahuja">Mukesh Ahuja</a>, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.</p> <p>“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”[[{"fid":"301378","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Mukesh Ahuja, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Mukesh Ahuja"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>There are currently two approved formulations: Oral capsules used for the treatment of <a href="https://emedicine.medscape.com/article/2055505-overview">interstitial cystitis</a> in the European Union, United States, and Australia and an injectable form used in Italy for thromboprophylaxis.<br/><br/>Dr. Ahuja <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424001225">presented data</a> from a <a href="https://clinicaltrials.gov/study/NCT04809376">phase 2 trial</a> that looked at the effect of once- or twice-weekly subcutaneous injections of PPS vs placebo in 61 people with knee OA pain. Assessments were made after 56, 168, and 365 days of treatment.<br/><br/>Results showed PPS injections resulted in significant improvements in total WOMAC score, WOMAC pain, and WOMAC function, with more PPS- than placebo-treated individuals achieving and then maintaining at least a 30% or greater improvement in pain and a 56% improvement in function.<br/><br/>Rescue medication use was lower in the PPS-treated patients, and Patient Global Impression of Change were significantly higher, Dr. Ahuja said.<br/><br/>Exploratory analyses of synovial fluid biomarkers showed PPS could be having a direct inflammatory effect, with reductions in several proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha.<br/><br/>An assessment of OA disease progression using MRI analysis suggested that there may be an effect on cartilage thickness and volume, as well as bone marrow lesions and overall joint inflammation.<br/><br/></p> <h2>Gene Therapy</h2> <p><a href="https://congress.oarsi.org/program/sessions/concurrent-session-7-clinical-aspects-and-outcomes-oa">Elsewhere at OARSI 2024</a>, <a href="https://www.sciencedirect.com/science/article/abs/pii/S1063458424001067">updated data</a> were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.</p> <p>Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a <a href="https://clinicaltrials.gov/study/NCT04124042">phase 2 trial</a>, which evaluated the effects of single and repeat IA injections of XT-150.<br/><br/><a href="https://acrabstracts.org/abstract/efficacy-of-xt-150-a-novel-non-viral-gene-therapy-delivering-il-10v-on-moderate-to-severe-pain-due-to-osteoarthritis-of-the-knee-results-of-a-phase-2-trial/">Previously</a>, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.[[{"fid":"301379","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Howard Rutman, chief medical officer of Xalud Therapeutics","field_file_image_credit[und][0][value]":"Sara Freeman/Medscape Medical News","field_file_image_caption[und][0][value]":"Dr. Howard Rutman"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.<br/><br/>Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (<em>P</em> = .044).<br/><br/>Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.<br/><br/>XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.<br/><br/></p> <h2>The Best Is Yet to Come?</h2> <p>“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.</p> <p>“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”<br/><br/>Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.<br/><br/>“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.<br/><br/>The congress was sponsored by the Osteoarthritis Research Society International.<br/><br/>Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/several-novel-injectables-show-early-promise-knee-2024a10008rh">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
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