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VIENNA — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.
After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
First Phase 3 Trial in China
“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.
Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.
“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.
But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).
“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.
“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
Standard Design
The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.
Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
Additional Results
Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.
There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.
As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.
Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.
There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.
Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.
As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.
“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
Another JAK in the Box?
Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.
Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”
Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”
The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
VIENNA — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.
After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
First Phase 3 Trial in China
“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.
Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.
“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.
But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).
“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.
“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
Standard Design
The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.
Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
Additional Results
Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.
There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.
As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.
Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.
There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.
Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.
As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.
“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
Another JAK in the Box?
Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.
Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”
Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”
The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
VIENNA — The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.
After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
First Phase 3 Trial in China
“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.
Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.
“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.
But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).
“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.
“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
Standard Design
The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.
Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
Additional Results
Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.
There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.
As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.
Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.
There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.
Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.
As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.
“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
Another JAK in the Box?
Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.
Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”
Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”
The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.
A version of this article appeared on Medscape.com.
FROM EULAR 2024