TLC Biopharmaceuticals, Inc. Reports Results Of Phase 1/2 Clinical Trial Of TLC599 For Sustained Pain Relief In The Treatment Of Osteoarthritis Of The Knee
TAIPEI, Taiwan – Jan. 6, 2017 – TLC (4152:TT) today reported top-line results from the Phase 1/2 trial of TLC599 for sustained pain management in patients with osteoarthritis of the knee. The trial demonstrated a positive safety profile for a single intra-articular injection of either a 6 mg or 12 mg dose of TLC599. In addition, the trial demonstrated a trend of sustained, clinically meaningful decrease from baseline through week 12 in several widely-used assessments of pain. These results support the potential for TLC599 to address the problem of a limited duration of action for steroid therapy in patients with osteoarthritis.
Therapies for osteoarthritis can be divided into approximately three categories depending on the severity of the disease. Often, physical therapy and non-steroidal anti-inflammatory drugs are used at early stages. As the disease progresses, injectable steroids are a typical treatment option. However, clinical practice guidelines advise against administering injections more than four times a year. These steroids only last for one to two weeks, meaning that many patients suffer from pain for months in between treatments.
“Aging populations across the globe are leading to an increased prevalence of osteoarthritis but current treatment options are inadequate,” commented TLC President George Yeh. “The results of this trial demonstrate that TLC599 may address the critical issue of short duration of action that limits the therapeutic potential of corticosteroid treatments in wide use today. We are encouraged by these results as we move ahead with our Phase 2 trial. We are optimistic that TLC599 will ultimately reduce burdens for patients and the healthcare system.”
The randomized, open-label, single-dose study of 40 patients found no significant adverse events over the 12 week period following injection. In addition, results in the 12 mg dose group demonstrated a trend of decrease from baseline in subject-rated Visual Analogue Scale (VAS) pain score at each study evaluation at week 1, 4, 8 and 12 (with a -3.14 point mean change from baseline at week 12; p=0.0156; per-protocol (PP) population), consistent with results in patients treated with the 6 mg dose (-1.95 point mean change from baseline at week 12; p=0.3125; PP). Results also demonstrated a trend of decrease relative to baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) A pain subset measurement at each study evaluation (a mean change of -3.75 points at week 12; p=0.0625; PP). These measurements were consistent with the trend observed in patients treated with the 6 mg dose (a mean change of -1.5 points from baseline in WOMAC A score; p=0.2500; PP). The positive safety profile and sustained efficacy observed in the trial support the potential of TLC599 for further development at 12 mg or higher doses.
TLC plans to initiate a Phase 2 trial of TLC599 at sites in Taiwan and Australia, with investigational new drug (IND) approval already granted in Taiwan by the Taiwan Food and Drug Administration (TFDA). The trial will involve 24 weeks of observation following a single intra-articular injection of TLC599 and investigate sustained control of pain for three groups: placebo, 12 mg and 18 mg, with 24 patients in each group. WOMAC measurements will be conducted at regular intervals over the observation period to evaluate efficacy of pain management. Data will be un-blinded once the 24 week data are available for all 72 patients. This Phase 2 clinical trial will help to determine the sample size and the efficacy period for a pivotal trial.
About TLC599
TLC599 encapsulates a corticosteroid using TLC’s sustained release BioSeizer platform. Current steroid treatments for osteoarthritis have potentially toxic side effects, and therefore, physicians advise against injecting these therapies more than three to four times per year. However, these steroids only have a duration of efficacy of one to two weeks, leaving patients in pain for the majority of the year. TLC599 is designed to keep pain at manageable levels in between four treatments over the course of one year, which is possible due to its rapid onset and sustained release capabilities.
In addition, current corticosteroid arthritis treatments induce chondrotoxicity, leading to the death of cartilage forming cells. Crystallized formulation of current treatments require added preservatives to prolong shelf life. These preservatives induce the death of chondrocytes, which means both the active pharmaceutical ingredient (API) and the excipient of current treatments exacerbate damage to the cartilage of the joint they are intended to treat. TLC599 is able to avoid the use of preservatives through terminal sterilization. Preclinical data demonstrated no chondrotoxicity three months after administration, meaning that with proper control and care, TLC599 can potentially delay or avoid the need for joint replacement.
About TLC
TLC is developing nanomedicines for the treatment of oncologic and ophthalmologic diseases as well as for the management of acute and chronic pain. The company’s proprietary Lipid-Assembled Delivery (LipAD™) technology is highly scalable and versatile, enabling the design of sustained release and targeted therapies capable of reducing toxicities and improving effectiveness. TLC’s advanced programs include TLC388 (Lipotecan), a first-in-class chemo-radiosensitizer for oncologic indications such as hepatocellular carcinoma and rectal cancer; ProDex (TLC399), a durable treatment for macular edema secondary to retinal vein occlusion and TLC599, a sustained release treatment for the management of pain associated with osteoarthritis.
For more information please visit www.tlcbio.com or follow us on Twitter @TLCbio.
Therapies for osteoarthritis can be divided into approximately three categories depending on the severity of the disease. Often, physical therapy and non-steroidal anti-inflammatory drugs are used at early stages. As the disease progresses, injectable steroids are a typical treatment option. However, clinical practice guidelines advise against administering injections more than four times a year. These steroids only last for one to two weeks, meaning that many patients suffer from pain for months in between treatments.
“Aging populations across the globe are leading to an increased prevalence of osteoarthritis but current treatment options are inadequate,” commented TLC President George Yeh. “The results of this trial demonstrate that TLC599 may address the critical issue of short duration of action that limits the therapeutic potential of corticosteroid treatments in wide use today. We are encouraged by these results as we move ahead with our Phase 2 trial. We are optimistic that TLC599 will ultimately reduce burdens for patients and the healthcare system.”
The randomized, open-label, single-dose study of 40 patients found no significant adverse events over the 12 week period following injection. In addition, results in the 12 mg dose group demonstrated a trend of decrease from baseline in subject-rated Visual Analogue Scale (VAS) pain score at each study evaluation at week 1, 4, 8 and 12 (with a -3.14 point mean change from baseline at week 12; p=0.0156; per-protocol (PP) population), consistent with results in patients treated with the 6 mg dose (-1.95 point mean change from baseline at week 12; p=0.3125; PP). Results also demonstrated a trend of decrease relative to baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) A pain subset measurement at each study evaluation (a mean change of -3.75 points at week 12; p=0.0625; PP). These measurements were consistent with the trend observed in patients treated with the 6 mg dose (a mean change of -1.5 points from baseline in WOMAC A score; p=0.2500; PP). The positive safety profile and sustained efficacy observed in the trial support the potential of TLC599 for further development at 12 mg or higher doses.
TLC plans to initiate a Phase 2 trial of TLC599 at sites in Taiwan and Australia, with investigational new drug (IND) approval already granted in Taiwan by the Taiwan Food and Drug Administration (TFDA). The trial will involve 24 weeks of observation following a single intra-articular injection of TLC599 and investigate sustained control of pain for three groups: placebo, 12 mg and 18 mg, with 24 patients in each group. WOMAC measurements will be conducted at regular intervals over the observation period to evaluate efficacy of pain management. Data will be un-blinded once the 24 week data are available for all 72 patients. This Phase 2 clinical trial will help to determine the sample size and the efficacy period for a pivotal trial.
About TLC599
TLC599 encapsulates a corticosteroid using TLC’s sustained release BioSeizer platform. Current steroid treatments for osteoarthritis have potentially toxic side effects, and therefore, physicians advise against injecting these therapies more than three to four times per year. However, these steroids only have a duration of efficacy of one to two weeks, leaving patients in pain for the majority of the year. TLC599 is designed to keep pain at manageable levels in between four treatments over the course of one year, which is possible due to its rapid onset and sustained release capabilities.
In addition, current corticosteroid arthritis treatments induce chondrotoxicity, leading to the death of cartilage forming cells. Crystallized formulation of current treatments require added preservatives to prolong shelf life. These preservatives induce the death of chondrocytes, which means both the active pharmaceutical ingredient (API) and the excipient of current treatments exacerbate damage to the cartilage of the joint they are intended to treat. TLC599 is able to avoid the use of preservatives through terminal sterilization. Preclinical data demonstrated no chondrotoxicity three months after administration, meaning that with proper control and care, TLC599 can potentially delay or avoid the need for joint replacement.
About TLC
TLC is developing nanomedicines for the treatment of oncologic and ophthalmologic diseases as well as for the management of acute and chronic pain. The company’s proprietary Lipid-Assembled Delivery (LipAD™) technology is highly scalable and versatile, enabling the design of sustained release and targeted therapies capable of reducing toxicities and improving effectiveness. TLC’s advanced programs include TLC388 (Lipotecan), a first-in-class chemo-radiosensitizer for oncologic indications such as hepatocellular carcinoma and rectal cancer; ProDex (TLC399), a durable treatment for macular edema secondary to retinal vein occlusion and TLC599, a sustained release treatment for the management of pain associated with osteoarthritis.
For more information please visit www.tlcbio.com or follow us on Twitter @TLCbio.