Allogeneic cell therapy fares well in phase III osteoarthritis trial

AMSTERDAM – A novel intra-articular allogeneic cell therapy improved knee osteoarthritis pain, physical activity, and patients’ quality of life in a randomized, placebo-controlled, double-blind, phase III trial reported at the World Congress on Osteoarthritis.

During a 1-year follow up, single-dose treatment with TissueGene C (Invossa) in patients with degenerative knee osteoarthritis (OA) led to significantly greater improvements in International Knee Documentation Committee (IKDC) knee pain, Likert visual analog scale (VAS) pain score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores than in those given a saline placebo.

©Nandyphotos/Thinkstock

The positive results of the trial, which was conducted exclusively in Korea, now pave the way for a similar phase III clinical trial to be run in the United States. The study design is being finalized and will follow the usual criteria for a phase III trial, but it will add one refinement on the design used in the Korean trial in that the TissueGene C (TG-C) will be given by image-guided intra-articular injection.

TG-C consists of two different populations of chondrocytes derived from a single human subject with polydactyly finger, of which one cell population has been genetically modified to express the gene for transforming growth factor-beta 1 (TGF-B1). It is a single-dose treatment that is intended to provide symptomatic relief and delay the structural progression of knee OA.

The proposed mode of action is that it targets cartilage degradation by enhancing chondrocyte proliferation, essentially improving cartilage structure by redirecting immune responses via effects on interleukin-10 and on M2 macrophages.

The target population is patients with with Kellgren-Lawrence grade II and III knee OA, Dr. Bumsup Lee of Kolon Life Science said during a company-sponsored symposium held during the congress, which was sponsored by Osteoarthritis Research Society International. Dr. Lee is chief operating officer of TissueGene Inc. in the United States, which is collaborating with Kolon Life Science, the Korean-based biochemical company that developed the novel OA therapy.

The aim is to develop a disease-modifying osteoarthritis drug (DMOAD) that fits criteria suggested by the Food and Drug Administration and the European Medicines Agency, Dr. Lee said. The clinical development program started in 2006, with phase I, II, and III studies now completed in Korea and phase II and III studies underway in the United States.

The results of the phase III Korean trial, which involved 163 patients, were presented during a poster session and during the industry-sponsored symposium. These showed that IKDC scores progressively increased (improved) for TG-C–treated patients from baseline through months 1, 3, 6, 9, and 12 with scores of 40.3, 42.9, 48.9, 53.2, 53.6, and 55.4, respectively, versus placebo scores at the same time points of 39.6, 44.6, 45.2, 36.5, 47.1, and 44.6. The differences became significant at 6 months. Changes in IKDC scores from baseline were also only significantly in favor of TG-C versus placebo starting at 6 months (12.9 vs. 6.9), then extending to 9 months (13.3 vs. 7.5) and 12 months (15.1 vs. 5.0).

TG-C proved superior to placebo in improving VAS pain scores at 6, 9, and 12 months, and changes in WOMAC scores were significant after 12 months with a mean change of –13.9 with TG-C and –6.2 with placebo.

The OMERACT-OARSI response rate was also assessed. A responder was identified as someone with an improvement in VAS pain score of 50% or more and an absolute change in score of at least 10 points and at least a 50% improvement in IKDC score with an absolute change of at least 20 points. The response rate for TG-C and placebo was 70% versus 52% (P = .02) at 6 months, 77% versus 52% at 9 months (P = .0011), and 84% versus 45% (P less than .001) at 12 months.

The most common adverse events seen were related to the intra-articular injection, Dr. Lee noted. Two serious adverse events – arthralgia and joint swelling – occurred in one subject who received the novel treatment, but this resolved within 10 days of administration.

Biomarker analyses have been performed and it appears that patients with greater joint space width, and higher baseline levels of CTX-II and C3M may be more likely to respond to TG-C. Some changes in CTX-I and CTX-II were clinically meaningful, and although the MRI data are still being evaluated, there was one striking feature: Patients treated with TG-C did not grow any osteophytes, compared with patients on placebo.

“Invossa holds great potential for a disease-modifying osteoarthritis drug,” said Dr. Gurdyal Kalsi, chief medical officer of TissueGene Inc. Based on the evidence today, which includes a phase II trial conducted in the United States (Osteoarthritis Cartilage. 2015;23:2109-18), he said that the novel treatment “offers sustained improvement of pain and function over 2 years with a single injection.” OMERACT-OARSI response rates were 81%-86% in patients not responding to conservative therapies in the phase II study.

It is envisioned that the phase III U.S. trial will start enrolling patients from the start of next year, with the last patient enrolled around May 2018 and the first results appearing around the summer of 2019. TissueGene Inc. would then expect to have the full trial results by 2020 and make a Biologics License Application to the FDA in early 2021.

“We believe we truly have something that we hope would fulfill a DMOAD application,” Dr. Kalsi said.

Kolon Life Science and TissueGene Inc. sponsored the studies. Dr. Lee and Dr. Kalsi are employees of TissueGene Inc.

AMSTERDAM – A novel intra-articular allogeneic cell therapy improved knee osteoarthritis pain, physical activity, and patients’ quality of life in a randomized, placebo-controlled, double-blind, phase III trial reported at the World Congress on Osteoarthritis.

During a 1-year follow up, single-dose treatment with TissueGene C (Invossa) in patients with degenerative knee osteoarthritis (OA) led to significantly greater improvements in International Knee Documentation Committee (IKDC) knee pain, Likert visual analog scale (VAS) pain score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores than in those given a saline placebo.

©Nandyphotos/Thinkstock

The positive results of the trial, which was conducted exclusively in Korea, now pave the way for a similar phase III clinical trial to be run in the United States. The study design is being finalized and will follow the usual criteria for a phase III trial, but it will add one refinement on the design used in the Korean trial in that the TissueGene C (TG-C) will be given by image-guided intra-articular injection.

TG-C consists of two different populations of chondrocytes derived from a single human subject with polydactyly finger, of which one cell population has been genetically modified to express the gene for transforming growth factor-beta 1 (TGF-B1). It is a single-dose treatment that is intended to provide symptomatic relief and delay the structural progression of knee OA.

The proposed mode of action is that it targets cartilage degradation by enhancing chondrocyte proliferation, essentially improving cartilage structure by redirecting immune responses via effects on interleukin-10 and on M2 macrophages.

The target population is patients with with Kellgren-Lawrence grade II and III knee OA, Dr. Bumsup Lee of Kolon Life Science said during a company-sponsored symposium held during the congress, which was sponsored by Osteoarthritis Research Society International. Dr. Lee is chief operating officer of TissueGene Inc. in the United States, which is collaborating with Kolon Life Science, the Korean-based biochemical company that developed the novel OA therapy.

The aim is to develop a disease-modifying osteoarthritis drug (DMOAD) that fits criteria suggested by the Food and Drug Administration and the European Medicines Agency, Dr. Lee said. The clinical development program started in 2006, with phase I, II, and III studies now completed in Korea and phase II and III studies underway in the United States.

The results of the phase III Korean trial, which involved 163 patients, were presented during a poster session and during the industry-sponsored symposium. These showed that IKDC scores progressively increased (improved) for TG-C–treated patients from baseline through months 1, 3, 6, 9, and 12 with scores of 40.3, 42.9, 48.9, 53.2, 53.6, and 55.4, respectively, versus placebo scores at the same time points of 39.6, 44.6, 45.2, 36.5, 47.1, and 44.6. The differences became significant at 6 months. Changes in IKDC scores from baseline were also only significantly in favor of TG-C versus placebo starting at 6 months (12.9 vs. 6.9), then extending to 9 months (13.3 vs. 7.5) and 12 months (15.1 vs. 5.0).

TG-C proved superior to placebo in improving VAS pain scores at 6, 9, and 12 months, and changes in WOMAC scores were significant after 12 months with a mean change of –13.9 with TG-C and –6.2 with placebo.

The OMERACT-OARSI response rate was also assessed. A responder was identified as someone with an improvement in VAS pain score of 50% or more and an absolute change in score of at least 10 points and at least a 50% improvement in IKDC score with an absolute change of at least 20 points. The response rate for TG-C and placebo was 70% versus 52% (P = .02) at 6 months, 77% versus 52% at 9 months (P = .0011), and 84% versus 45% (P less than .001) at 12 months.

The most common adverse events seen were related to the intra-articular injection, Dr. Lee noted. Two serious adverse events – arthralgia and joint swelling – occurred in one subject who received the novel treatment, but this resolved within 10 days of administration.

Biomarker analyses have been performed and it appears that patients with greater joint space width, and higher baseline levels of CTX-II and C3M may be more likely to respond to TG-C. Some changes in CTX-I and CTX-II were clinically meaningful, and although the MRI data are still being evaluated, there was one striking feature: Patients treated with TG-C did not grow any osteophytes, compared with patients on placebo.

“Invossa holds great potential for a disease-modifying osteoarthritis drug,” said Dr. Gurdyal Kalsi, chief medical officer of TissueGene Inc. Based on the evidence today, which includes a phase II trial conducted in the United States (Osteoarthritis Cartilage. 2015;23:2109-18), he said that the novel treatment “offers sustained improvement of pain and function over 2 years with a single injection.” OMERACT-OARSI response rates were 81%-86% in patients not responding to conservative therapies in the phase II study.

It is envisioned that the phase III U.S. trial will start enrolling patients from the start of next year, with the last patient enrolled around May 2018 and the first results appearing around the summer of 2019. TissueGene Inc. would then expect to have the full trial results by 2020 and make a Biologics License Application to the FDA in early 2021.

“We believe we truly have something that we hope would fulfill a DMOAD application,” Dr. Kalsi said.

Kolon Life Science and TissueGene Inc. sponsored the studies. Dr. Lee and Dr. Kalsi are employees of TissueGene Inc.

AMSTERDAM – A novel intra-articular allogeneic cell therapy improved knee osteoarthritis pain, physical activity, and patients’ quality of life in a randomized, placebo-controlled, double-blind, phase III trial reported at the World Congress on Osteoarthritis.

During a 1-year follow up, single-dose treatment with TissueGene C (Invossa) in patients with degenerative knee osteoarthritis (OA) led to significantly greater improvements in International Knee Documentation Committee (IKDC) knee pain, Likert visual analog scale (VAS) pain score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores than in those given a saline placebo.

©Nandyphotos/Thinkstock

The positive results of the trial, which was conducted exclusively in Korea, now pave the way for a similar phase III clinical trial to be run in the United States. The study design is being finalized and will follow the usual criteria for a phase III trial, but it will add one refinement on the design used in the Korean trial in that the TissueGene C (TG-C) will be given by image-guided intra-articular injection.

TG-C consists of two different populations of chondrocytes derived from a single human subject with polydactyly finger, of which one cell population has been genetically modified to express the gene for transforming growth factor-beta 1 (TGF-B1). It is a single-dose treatment that is intended to provide symptomatic relief and delay the structural progression of knee OA.

The proposed mode of action is that it targets cartilage degradation by enhancing chondrocyte proliferation, essentially improving cartilage structure by redirecting immune responses via effects on interleukin-10 and on M2 macrophages.

The target population is patients with with Kellgren-Lawrence grade II and III knee OA, Dr. Bumsup Lee of Kolon Life Science said during a company-sponsored symposium held during the congress, which was sponsored by Osteoarthritis Research Society International. Dr. Lee is chief operating officer of TissueGene Inc. in the United States, which is collaborating with Kolon Life Science, the Korean-based biochemical company that developed the novel OA therapy.

The aim is to develop a disease-modifying osteoarthritis drug (DMOAD) that fits criteria suggested by the Food and Drug Administration and the European Medicines Agency, Dr. Lee said. The clinical development program started in 2006, with phase I, II, and III studies now completed in Korea and phase II and III studies underway in the United States.

The results of the phase III Korean trial, which involved 163 patients, were presented during a poster session and during the industry-sponsored symposium. These showed that IKDC scores progressively increased (improved) for TG-C–treated patients from baseline through months 1, 3, 6, 9, and 12 with scores of 40.3, 42.9, 48.9, 53.2, 53.6, and 55.4, respectively, versus placebo scores at the same time points of 39.6, 44.6, 45.2, 36.5, 47.1, and 44.6. The differences became significant at 6 months. Changes in IKDC scores from baseline were also only significantly in favor of TG-C versus placebo starting at 6 months (12.9 vs. 6.9), then extending to 9 months (13.3 vs. 7.5) and 12 months (15.1 vs. 5.0).

TG-C proved superior to placebo in improving VAS pain scores at 6, 9, and 12 months, and changes in WOMAC scores were significant after 12 months with a mean change of –13.9 with TG-C and –6.2 with placebo.

The OMERACT-OARSI response rate was also assessed. A responder was identified as someone with an improvement in VAS pain score of 50% or more and an absolute change in score of at least 10 points and at least a 50% improvement in IKDC score with an absolute change of at least 20 points. The response rate for TG-C and placebo was 70% versus 52% (P = .02) at 6 months, 77% versus 52% at 9 months (P = .0011), and 84% versus 45% (P less than .001) at 12 months.

The most common adverse events seen were related to the intra-articular injection, Dr. Lee noted. Two serious adverse events – arthralgia and joint swelling – occurred in one subject who received the novel treatment, but this resolved within 10 days of administration.

Biomarker analyses have been performed and it appears that patients with greater joint space width, and higher baseline levels of CTX-II and C3M may be more likely to respond to TG-C. Some changes in CTX-I and CTX-II were clinically meaningful, and although the MRI data are still being evaluated, there was one striking feature: Patients treated with TG-C did not grow any osteophytes, compared with patients on placebo.

“Invossa holds great potential for a disease-modifying osteoarthritis drug,” said Dr. Gurdyal Kalsi, chief medical officer of TissueGene Inc. Based on the evidence today, which includes a phase II trial conducted in the United States (Osteoarthritis Cartilage. 2015;23:2109-18), he said that the novel treatment “offers sustained improvement of pain and function over 2 years with a single injection.” OMERACT-OARSI response rates were 81%-86% in patients not responding to conservative therapies in the phase II study.

It is envisioned that the phase III U.S. trial will start enrolling patients from the start of next year, with the last patient enrolled around May 2018 and the first results appearing around the summer of 2019. TissueGene Inc. would then expect to have the full trial results by 2020 and make a Biologics License Application to the FDA in early 2021.

“We believe we truly have something that we hope would fulfill a DMOAD application,” Dr. Kalsi said.

Kolon Life Science and TissueGene Inc. sponsored the studies. Dr. Lee and Dr. Kalsi are employees of TissueGene Inc.