Arthritis and Arthritic Pain
December 12, 2016
Pfizer announced new results from phase III studies of Xeljanz (tofacitinib citrate) in adult patients with active psoriatic arthritis (PsA) who had an inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to tumor necrosis factor inhibitors (TNFis), respectively. OPAL Broaden, which was a 12-month duration trial with a three month placebo-controlled period, evaluated the efficacy and safety of tofacitinib 5mg (n=107) and 10mg (n=104) BID compared to placebo (n=105) in adult patients with active PsA who had an IR to at least one csDMARD and who were TNFi-naïve. OPAL Broaden included an active control arm of adalimumab 40mg (n=106) administered subcutaneously every two weeks (q2 wk). The study was not designed for non-inferiority or superiority comparisons between adalimumab and tofacitinib. OPAL Beyond, a six-month duration trial with a three month placebo-controlled period, evaluated the efficacy and safety of tofacitinib 5mg (n=131) and 10mg (n=132) BID compared to placebo (n=131) in adult patients with active PsA who had an IR to at least one TNFi. OPAL Beyond focused exclusively on the TNFi-IR patient population. In both studies, patients who were initially randomized to placebo advanced to tofacitinib 5 or 10mg BID in a blinded manner at three months. OPAL Broaden and OPAL Beyond met their primary efficacy endpoints showing a statistically significant improvement with tofacitinib 5mg and 10mg BID compared to treatment with placebo at three months as measured by American College of Rheumatology 20 (ACR20) response (OPAL Broaden: p=0.05 and p<0.0001; OPAL Beyond: p<0.0001, respectively), and change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) score (OPAL Broaden: p=0.05 and p<0.001; OPAL Beyond: p<0.0001 and p<0.001, respectively).
August 15, 2016
Ablynx issued results of a phase IIb trial of vobarilizumab for patients with moderate to severe rheumatoid arthritis (RA) already being treated with methotrexate (MTX). The double-blind study enrolled 345 subjects randomly assigned to one of the four dose groups of subcutaneously (sc) administered vobarilizumab plus methotrexate [75mg every four weeks (Q4W), 150mg Q4W, 150mg Q2W, 225mg Q2W] or placebo plus methotrexate. Subjects were evaluated for efficacy up to and including week 24, and for safety up to and including week 34. Following completion of the 24-week treatment period, eligible subjects were invited to enroll in an open-label extension study of vobarilizumab, with 94% accepting. Subjects who were not eligible to roll over or who did not elect to do so were followed for safety for an additional 12 weeks after the last dosing. Evaluation is ongoing for a minority of these subjects. At week 12, a 20% improvement in American College of Rheumatology scores (ACR20), the primary endpoint of the study, was seen in up to 81% of vobarilizumab-treated patients. From week 12 to week 24, vobarilizumab induced continued improvement in higher-level responses with ACR50 and ACR70 scores of up to 59% and 43% respectively at week 24. Moreover, the results demonstrate that vobarilizumab has a rapid and strong impact on disease activity with up to 49% of vobarilizumab-treated patients achieving clinical remission at week 24 compared to 17% of patients receiving placebo. The company plans to initiate a phase III program before year’s end.
April 11, 2016
Eli Lilly reported results of a phase III trial of baricitinib for moderate-to-severe rheumatoid arthritis (RA). The RA-BEACON study enrolled 527 patients who previously had failed at least one tumor necrosis factor (TNF) inhibitor, and included 199 patients who also had received prior treatment with one or more non-anti-TNF biologic agents. Patients received baricitinib 2mg or 4mg or placebo daily, in addition to their existing background therapies, for 24 weeks. The study met its primary endpoint of improved ACR 20 response for baricitinib compared with placebo at week 12. ACR 20 represents at least a 20% improvement across selected measures of disease activity. ACR 20 response rates were as follows (P≤0.001 for each baricitinib dose versus placebo): 55% for baricitinib 4mg, 49% for baricitinib 2mg and 27% for placebo. A statistically significant improvement in ACR 20 response rate with baricitinib versus placebo was observed as early as one week (P≤0.01). ACR 50 and ACR 70 response rates were also significantly higher for baricitinib compared with placebo at week 12 (P≤0.01). A significantly greater proportion of patients treated with baricitinib also achieved a DAS28-CRP scorea measure of RA disease activitybelow 2.6 (indicating disease remission) at week 12 compared with patients receiving placebo. Additionally, a greater proportion of patients treated with baricitinib versus placebo achieved score improvements of at least 0.3 on the Health Assessment Questionnaire Disability Index (HAQ-DI), a patient-reported assessment of physical function at week 12. Significant improvements in ACR response rates, DAS28-CRP and HAQ-DI that were noted with baricitinib versus placebo at week 12 were maintained through week 24. Through 24 weeks, the rate of treatment-emergent adverse events (AEs) was higher for baricitinib 4mg (77%) and baricitinib 2mg (71%) than for placebo (64%).
January 25, 2016
Sorrento Therapeutics reported results of a phase III study of STI-002 in China for the treatment of rheumatoid arthritis (RA). The randomized, controlled, two-part phase III enrolled 330 patients. STI-002 demonstrated an improvement in RA patients’ pain symptoms, functions, quality-of-life and inflammation markers, while also inhibiting bone and joint injuries. STI-002 (3mg/kg) plus MTX demonstrated significant improvement in ACR 20, 50 and 70 (77%, 50% and 20% respectively), similar clinical efficacy reported for Remicade and biosimilars of Remicade. Notably, the immunogenicity and anti-drug antibody formation (ADA) is drastically reduced for STI-002 compared to Remicade (<5% v. ~40%). While MabTech is applying for marketing approval of STI-001 and STI-002 in China, Sorrento Biologics, a wholly-owned subsidiary of Sorrento Therapeutics, is expediting efforts for the development and commercialization of STI-002 in Sorrento territory, including the North America, Europe and Japan.
November 23, 2015
Regeneron Pharmaceuticals and Sanofi have announced results from a pivotal phase III study of sarilumab for treatment of rheumatoid arthritis (RA). The SARIL-RA-TARGET trial enrolled 546 RA patients who were inadequate responders or intolerant of TNF-alpha inhibitors (TNF-IR). Patients were randomized to one of three treatment groups self-administered subcutaneously every other week: sarilumab 200 milligrams (mg), sarilumab 150mg, or placebo, in addition to non-biologic disease modifying anti-rheumatic drugs (DMARD) therapy. The change from baseline to week 12 in Health Assessment Questionnaire-Disability Index (HAQ-DI) was -0.49, -0.50, and -0.29 in the sarilumab 200mg (p=0.0004), sarilumab 150mg (p=0.0007), and placebo groups, respectively. Improvements in signs and symptoms of RA at week 24, as measured by the proportion of patients achieving an ACR20 response (ACR20) were 61% in the sarilumab 200mg group; 56% in the sarilumab 150mg group; and 34% in the placebo group, all in combination with DMARD therapy (p<0.0001). Proportion of patients achieving an ACR50 response at week 24 were 41% in the sarilumab 200mg group, 37% in the sarilumab 150mg group, and 18% in the placebo group (p<0.0001). Treatment-emergent adverse events (TEAEs) were more frequent in the sarilumab groups (65% and 66% in sarilumab 200mg and 150mg v. 50% in placebo, respectively). The incidence of serious adverse events (SAEs) was higher than placebo in the sarilumab 200mg group (5% v. 3%) and was similar to placebo in the 150mg group (3%). Infection was the most frequently reported adverse event (30%, 22% and 27% in the 200mg, 150mg and placebo groups, respectively). Sanofi and Regeneron recently submitted a BLA for sarilumab to the FDA.
November 16, 2015
Amgen has released results of a phase III
study of ABP 501 with adalimumab in patients
with moderate-to-severe rheumatoid arthritis.
The randomized, double-blind, active-controlled
study randomized subjects to
receive either 40mg ABP 501 subcutaneous injection
(SC) every two weeks (n=264) or 40mg
SC adalimumab every two weeks (n=262) until
week 22. The study was completed at week 24,
followed by a safety follow-up period through
to week 26. The study met the primary endpoint,
which was achievement of ACR20 (20%
or greater improvement in ACR assessment) at
week 24. At week 24, 74.6% of patients in the
ABP 501 group and 72.4% in the adalimumab
group met the ACR20 response criteria. The
risk ratio of ACR20 was 1.039 with the twosided
90% CI of 0.954-1.133, which fell within
the predefined equivalence margin. Secondary
endpoints included the achievement of ACR50
and ACR70 (a 50 or 70% improvement in ACR
assessment) within the predefined equivalence
margin. At week 24, patients treated
with ABP 501 compared with those treated
with adalimumab achieved ACR50 (49.2% v.
52%) and ACR70 (26% v. 22.9%), respectively.
Additionally, the secondary endpoint of a difference
in change from baseline of DAS28-CRP
(Disease Activity Score examines 28 joints in
the body as measured by C reactive protein
in the blood) over the entire study also was
achieved. The difference in mean change from
baseline in DAS28-CRP between ABP 501
and adalimumab was -0.01 (90% CI, -0.18 to
0.17) at week 24. The incidence of treatment-emergent
adverse events (TEAEs) was 50% for
ABP 501 and 55% for adalimumab. The most
frequently reported TEAEs (for ABP 501 and
adalimumab, respectively) were nasopharyngitis
(6.4% v. 7.3%), headache (4.5% v. 4.2%),
arthralgia (3% v. 3.4%), cough (2.7% v. 3.1%)
and upper respiratory tract infection (1.5% v.
October 26, 2015
Novartis has issued results of a phase III study
of secukinumab for psoriatic arthritis (PsA).
FUTURE 1 was a first multicenter, randomized,
placebo-controlled study evaluating the efficacy
and safety of secukinumab in PsA. The study
enrolled 606 patients with active PsA, including
patients who previously had been treated with
DMARDs (disease-modifying anti-rheumatic
drugs) and patients who had an inadequate
response or did not tolerate anti-tumor necrosis
factor (anti-TNF) drugs, and assessed
secukinumab with intravenous loading (10mg/
kg) and subcutaneous (75mg and 150mg) maintenance
dosing. In the study, patients received
an intravenous loading dose every two weeks
for the first four weeks of treatment followed by
monthly subcutaneous doses of 75mg or 150mg
compared to placebo. The study met its primary
endpoint, the American College of Rheumatology
response criteria (ACR 20), at week 24. Results
showed half of patients (50.0% and 50.5%) in
both secukinumab-treated dose groups (150mg
and 75mg; p<0.001) achieved ACR 20 response
compared with only 17.3% of placebo patients.
Exploratory analyses showed more secukinumab-
treated patients in the 150mg and 75mg dose
groups experienced ACR 20 responses by week
one v. placebo (p<0.001). Secukinumab was
well-tolerated in the study, with a safety profile
generally consistent with that observed in the
psoriasis clinical trial program. The most common
adverse events (AEs) for either secukinumab dose
were the common cold (nasopharyngitis, 8.2%),
headache (5.4%) and upper respiratory tract
infections (5.4%). In FUTURE 1, 64.9% (150 mg),
60.4% (75 mg), and 58.4% (placebo) of patients
reported an AE. Serious adverse event (SAE) rates
were 4.5%, 2.5%, and 5.0%, respectively.
February 16, 2015
Amgen reported results of a phase III trial
of biosimilar candidate ABP 501 compared
with Humira (adalimumab) in patients with
moderate-to-severe rheumatoid arthritis. The
randomized, double-blind, active-controlled
study evaluated safety, efficacy and immunogenicity
of ABP 501 compared to adalimumab
in adult patients with moderate-to-severe
rheumatoid arthritis who have an inadequate
response to methotrexate. The study consisted
of a screening period of four weeks and a treatment
period of 22 weeks, followed by a safety
follow-up period through to week 26. There
were 526 patients enrolled. Among them, 264
patients were randomized to receive ABP 501
40mg subcutaneous (SC) every two weeks
and 262 patients were randomized to receive
adalimumab 40mg SC every two weeks.
The primary endpoint compared the ACR20
measurements (20% or greater improvement
in ACR assessment) at week 24. The ACR20 was
within the prespecified margin for ABP 501
compared to adalimumab, showing clinical
equivalence. Safety and immunogenicity of
ABP 501 were comparable to adalimumab.
December 8, 2014
Novartis has reported results of two
phase III trials of AIN457 (secukinumab) for
psoriatic arthritis (PsA). Statistically significant
improvements in signs and symptoms of PsA
were achieved with secukinumab v. placebo at
week 24. Between 50% to 54% of secukinumab
patients achieved American College of
Rheumatology (ACR20) response criteria in
both FUTURE 1 (p<0.0001) and FUTURE 2
(p<0.0001). This is in comparison to 17.3%
and 15.3% of placebo patients who achieved
ACR20, respectively. Exploratory analyses in
FUTURE 1 showed more secukinumab-treated
patients in the 75mg (20.3%) and 150mg
(20.8%) dose groups experienced ACR20
responses by week one v. placebo (5.4%)
(p<0.0001). In FUTURE 2, more secukinumabtreated
patients in the 150mg (42.0%) and
300mg (37.0%) dose groups experienced
ACR20 responses by week three (150mg
p<0.0001; 300mg p<0.001) v. placebo (15.3%);
secukinumab-treated patients who received
the 75mg (23.2%) dose did not achieve a
statistically significant response. Secukinumab
was well-tolerated in both studies.
June 23, 2014
Sanofi and Regeneron Pharmaceuticals
reported phase III trial results of sarilumab
for rheumatoid arthritis (RA). The phase III
trial enrolled 1,197 adult patients with
active, moderate-to-severe RA, who were
inadequate responders to MTX therapy.
Patients were randomized to one of three
treatment groups dosed subcutaneously
every other week, sarilumab 150mg, sarilumab
200mg or placebo, all in combination
with MTX. Both sarilumab groups showed
statistically significant improvements
compared to the placebo group (p<0.0001).
Improvement in signs and symptoms of RA
at 24 weeks, as measured by the American
College of Rheumatology score of 20%
improvement showed 58%, 66% and 33% in
the sarilumab 150mg, sarilumab 200mg and
placebo groups, respectively. Improvement
in physical function at week 16 as measured
by Health Assessment Questionnaire—
Disability Index (HAQ-DI) showed -0.53,
-0.55 and -0.29 in the sarilumab 150mg, sarilumab
200mg and placebo groups, respectively.
Inhibition of progression of structural
damage at week 52, as measured by change
in the van der Heijde modified total Sharp
score (mTSS), showed results were 0.90, 0.25
and 2.78 in the sarilumab 150mg, sarilumab
200mg and placebo groups, respectively. The
group receiving the 200mg dose of sarilumab
had a reduction of approximately 90%
in the radiographic progression assessed
by the mTSS, compared to the radiographic
progression with placebo at week 52. The
sarilumab phase III program has six ongoing
clinical studies and is targeted to enroll
approximately 2,800 RA patients.
November 18, 2013
Bristol-Myers Squibb released results of a
phase IIb trial of study of subcutaneous (SC)
clazakizumab in adults with moderateto-
severe rheumatoid arthritis (RA) and an
inadequate response to methotrexate (MTX).
This was a randomized, dose-ranging study of
clazakizumab subcutaneous injection alone or in combination with methotrexate (MTX). The study included 418 adults in 115 sites throughout North and South America, Europe and Asia. Participants were randomized to one of seven treatment arms: once monthly clazakizumab 25mg, 100mg or 200mg, all on MTX background; once monthly clazakizumab 100mg or 200mg without MTX; MTX alone; or twice monthly adalimumab 40mg + MTX. At week 12, ACR20 response rates (the primary endpoint) were: 78%, clazakizumab 25mg + MTX (p<0.001); 71.7%, clazakizumab 100mg + MTX (p<0.001); 60%, clazakizumab 200mg + MTX (p=0.015); 55.0%, clazakizumab 100mg alone (p=0.042); 61%, clazakizumab 200mg alone (p=0.015); v. 39.3%, MTX. The ACR20 response rate for adalimumab 40mg + MTX was 76.3%.
September 9, 2013
EPIRUS Biopharmaceuticals released results of a phase III trial of infliximab molecule BOW-015 for the treatment of rheumatoid arthritis (RA). This phase III trial was a double-blind, active comparator study of the efficacy and safety of BOW-015 in patients with severe and active rheumatoid arthritis on stable doses of methotrexate. Subjects were randomized two to one in favor of BOW-015 (Total N= 189 subjects; 127 BOW-015: 62 Remicade). Patients received infusions of either BOW-015 (3mg/kg) or Remicade (3mg/kg) using the approved Remicade dosing regimen. Starting at week 22, responders were crossed over into a single BOW-015 arm in an open-label phase. All patients will be followed for a total of 54 weeks in this open-label phase. BOW-015 achieved a week 16 ACR20 response rate of 89.8%, compared to 86.4% for Remicade. No meaningful differences were observed in safety or immunogenicity. Plans are to submit regulatory filings in targeted emerging markets over the next year.
June 24, 2013
Janssen issued results from a phase III trial of STELARA (ustekinumab) for active psoriatic arthritis. Patients were naïve to treatment with anti-TNF-alpha therapies and/or IL-12/23 inhibitors. This multicenter, randomized, double-blind, placebo-controlled study enrolled 615 subjects who had at least five tender and five swollen joints and C-reactive protein (CRP) levels of at least 0.3mg/dL (upper limit of normal [ULN] 1.0 mg/dL) despite treatment with disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were randomized to receive subcutaneous STELARA 45mg or 90mg or placebo at weeks zero, four and then every 12 weeks. By week 24, all patients receiving placebo were crossed over to receive STELARA. At week 24, 42.4% and 49.5% of patients receiving STELARA 45mg and 90mg, respectively, achieved at least 20% improvement in signs and symptoms, according to the American College of Rheumatology criteria (ACR 20), the primary endpoint, compared with 22.8% of patients receiving placebo (P < 0.0001 for both comparisons). Improvement in signs and symptoms continued to increase after week 24, with 55.7% and 60.3% of patients in the STELARA 45mg and STELARA 90mg groups, respectively, demonstrating ACR 20 response at week 52. Janssen is seeking approval of STELARA in the U.S. and Europe.
June 17, 2013
Rigel Pharmaceuticals and AstraZeneca reported results from OSKIRA-2 and OSKIRA- 3, phase III trials of fostamatinib for the treatment of rheumatoid arthritis. In the OSKIRA-2 study of patients inadequately responding to disease modifying anti-rheumatic drugs (DMARDs), fostamatinib in combination with DMARDs showed statistically significant improvements in ACR20 response rates at 24 weeks in both the 100mg twice daily (bid) group and the group receiving 100mg bid for four weeks followed by 150mg once daily (qd) compared to placebo. In the OSKIRA-3 study of patients inadequately responding to methotrexate (MTX) and a single TNF-alpha antagonist, fostamatinib in combination with MTX showed statistically significant improvements in ACR20 response rates at 24 weeks in the 100mg bid group,
but not in the group given 100mg bid for
four weeks followed by 150mg qd compared
to placebo. Fostamatinib continues to be well
tolerated by patients. Based on the totality of
the results, AZ has decided it will not proceed
with regulatory filings and will return the
rights to the compound to Rigel.
May 13, 2013
Celgene International reported results from a phase III trial of apremilast for the treatment of psoriatic arthritis. This multi-center, double-blind, placebo-controlled, parallel-group study enrolled over 500 patients with psoriatic arthritis. Subjects received apremilast 20mg or 30mg twice daily, or placebo, for 24 weeks, with a subsequent extension in which all patients are treated with apremilast. Data demonstrated statistical significance was achieved for the primary endpoint of ACR 20 at week 16 for patients receiving apremilast 20mg and 30mg. Patients on apremilast also achieved a statistically significant benefit over placebo in key secondary endpoints: various measures of physical function and signs and symptoms. The drug was well tolerated. The most frequent adverse events were nausea, diarrhea and headache. Based on this data, Celgene expects to file a separate NDA in the U.S. for psoriasis and a combined PsA/psoriasis MAA submission in Europe in the second half of 2013.
February 18, 2013
Ablynx issued results from a phase II trial of ALX-0061 for the treatment of rheumatoid arthritis (RA). This randomized, placebo-controlled, dose-escalation study enrolled 37 patients with moderately to severely active RA who also were on a stable background of methotrexate. Subjects received ALX-0061 1mg/kg every four weeks (Q4W), 3mg/kg Q4W or 6mg/kg Q8W, or placebo, for 24 weeks. Depending on the patient’s disease status at week 10, the monthly dose was increased (from 1mg/kg to 3mg/kg; or from 3mg/kg to 6mg/kg) or intensified (from 6mg/kg Q8W to 6 mg/kg Q4W). Results showed, of the unmodified ALX-0061 patient population, 50% (1mg/kg), 75% (3mg/kg), and 63% (6mg/kg) achieved DAS28 remission. Furthermore, 50% of the modified ALX-0061 patient population achieved DAS28 remission. ALX-0061 was well-tolerated. There were no clinically relevant neutropenia, clinically significant increases in lipid levels or serious infections. Ablynx is in discussions with potential partners.
January 7, 2013
Novartis published results of a phase III trial of ACZ885 (canakinumab) for the treatment of systemic juvenile idiopathic arthritis (SJIA). This four-week, randomized, double-blind, placebo-controlled study, Beta-SPECIFIC 1, enrolled 84 patients between ages two and 19 with active SJIA. Subjects received a single subcutaneous dose of 4mg/kg (up to 300mg) ACZ885 or placebo. Data demonstrated 84% of patients treated with ACZ885 experienced at least a 30% improvement in symptoms compared to 10% for placebo after 15 days of treatment, which was sustained after 29 days (p<0.001). Additionally, ACZ885-treated patients were nearly three times less likely to experience a new flare, with 74% of ACZ885-treated patients remaining flare-free, compared to 25% with placebo (p=0.003). The drug was well tolerated. Based on these data, Novartis pursued regulatory submission in the U.S. and Europe.
November 19, 2012
Galapagos released results from a phase IIa trial of GLPG0634 for the treatment of rheumatoid arthritis (RA). This four-week, multi-center, multi-arm study enrolled 91 patients with active RA showing an insufficient response to the standard-of-care treatment, methotrexate (MTX). Subjects received GLPG0634 30mg, 75mg, 150mg or 300mg daily or placebo for four weeks. All subjects continued to receive MTX during the study. Results showed GLPG0634 achieved statistically significant improvement in CRP (C-reactive protein), DAS28, HAQ-DI, ACR20 and ACR50 response rates at the 300mg dose. Efficacy endpoints showed a rapid onset and sustained effect until the end of the study. GLPG0634 was well-tolerated. No serious adverse events were reported. Based on these results, Galapagos will move GLPG0634 into global phase IIb trials early next year.
October 1, 2012
MorphoSys released results from a phase Ib/IIa trial of MOR103 for the treatment of rheumatoid arthritis (RA). This randomized, double-blind, placebo-controlled study enrolled 96 patients with mild to moderate RA. Subjects received MOR103 0.3mg/kg, 1.0mg/kg or 1.5mg/kg, or placebo, weekly for four weeks. Data demonstrated that the best response was achieved in the 1.0mg/kg dose cohort with an ACR20 score of 68% at week four, significantly higher than in the control arm (p<0.0001). Importantly, MOR103 had a fast onset: within two weeks, up to 40% of patients achieved an ACR20 score. Improvement of DAS28 scores was rapid and significant over the treatment period of the study as well. MRI scans revealed a reduction of synovitis, according to the RAMRIS system, at week four. MOR103 was well tolerated. Based on these data, MorphoSys will seek a commercial partner for further development of the program. The company will also submit a late-breaking abstract for a forthcoming conference.
September 24, 2012
Pfizer released preliminary results from a phase III trial of tofacitinib for rheumatoid arthritis (RA). This ongoing, two-year, randomized study enrolled methotrexate (MTX-naïve patients with moderate-to-severe active rheumatoid arthritis. Subjects received tofacitinib 5mg or 10mg twice-daily (BID) or MTX. Results showed tofacitinib met its primary endpoint and was found to be superior to MTX. Statistically significant changes were seen in inhibiting structural damage as measured by change from baseline in van der Heijde modified Total Sharp Score (mTSS) and in reducing signs and symptoms of RA as measured by ACR70 response rates, both assessed at six months. Secondary endpoints, including ACR20 and ACR50 responses, DAS-defined remission (DAS28-4(ESR)<2.6), and mean change in HAQ-DI, were statistically significantly greater with tofacitinib versus MTX at all time points. The drug was well tolerated. Tofacitinib is currently under review by several regulatory agencies (the U.S., Europe and Japan). If approved, tofacitinib would be the first RA treatment in a new class of medicines known as JAK inhibitors and the first new oral disease-modifying antirheumatic drug (or DMARD) for RA in more than 10 years.
September 3, 2012
Protalex released results from a phase Ib trial of PRTX-100 for the treatment of rheumatoid arthritis (RA). This randomized, multiple-dose, dose-escalation study enrolled 37 patients already being treated with methotrexate. Subjects were divided into four arms and received 0.15μg/kg to 1.50μg/kg PRTX-100 or placebo weekly for four weeks. The primary disease activity response endpoint was the number of patients with a DAS28-CRP <3.2 at week six. Results showed the PRTX-100 patients as a group had more responders than placebo at all times, that responders increased over time during the 16-week study evaluation period and that the maximum tolerated dose was not reached at the highest dose level. Additionally, PRTX-100 did not decrease CRP (C-Reactive Protein) levels, even in those patients whose swollen and tender joint count and global VAS (Visual Analogue Scale) scores had decreased to low levels after treatment. The drug was well tolerated. Based on these data, Protalex is planning a trial of PRTX-100 at doses of 1.50µg/kg and higher in the U.S. and South Africa.
August 27, 2012
Lexicon Pharmaceuticals reported preliminary results from a phase I study of LX2931 for the treatment of rheumatoid arthritis. This randomized, dose-ranging, placebo-controlled study enrolled 10 patients. Subjects received increasing doses over the course of the study, beginning at 50mg once daily (QD) and escalating to 500mg QD, or placebo, for 12 weeks. Seven of eight patients on LX2931 achieved drug trough levels greater than 60ng/ml. Six of the eight LX2931-treated patients experienced a drop from baseline in the DAS28 score of greater than or equal to 1.2, as did both placebo patients. ACR20 and ACR50 responses were achieved at varying frequencies in both LX2931-treated and placebo patients, but two of eight patients dosed with LX2931 achieved an ACR70 response during the course of the study, compared to none on placebo. The drug was well-tolerated at all doses evaluated. Based on these data, Lexicon may pursue evaluation LX2931 at higher doses.
August 13, 2012
Array BioPharma released results from a phase II trial of ARRY-797 for the treatment of moderate to severe chronic knee pain despite the use of non-steroidal anti-inflammatory drugs (NSAIDs). This randomized, placebo-controlled and active controlled study enrolled 157 patients with osteoarthritis. Subjects were divided (1:1:1) to receive ARRY-797, placebo or oxycodone ER while continuing their use of NSAIDs for four weeks. Data showed a statistically significant reduction in pain compared to placebo, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Patients receiving ARRY-797 experienced a mean reduction in the WOMAC pain subscale score at day 28 vs. baseline that was 0.8 greater than those receiving placebo (2.4 vs. 1.6; one-sided p=0.0247). ARRY-797 was well tolerated. The most frequent adverse events were dizziness, diarrhea and nausea. Array will begin seeking a partner to maximize the value of ARRY-797.
Protalex reported results from a phase Ib trial of PRTX-100 for the treatment of rheumatoid arthritis (RA). This randomized, multiple-dose, dose-escalation study enrolled 37 patients who were also being treated with methotrexate. Subjects were divided into four dose-escalating cohorts and received PRTX-100 ranging 0.15μg/kg to 1.50μg/kg or placebo once a week for four weeks. Data demonstrated the need for further study of PRTX-100 at doses of 1.50μg/kg and higher. The drug was found to be safe and well tolerated. Protalex will commence a higher dose-escalation study once analysis of this study is complete.
July 2, 2012
Ablynx released results from a phase II trial of ozoralizumab for the treatment of rheumatoid arthritis. The open-label extension study enrolled 266 patients who had an insufficient response to methotrexate alone and had participated in the company’s previous two phase II studies. Subjects received ozoralizumab by a subcutaneous injection every four weeks (Q4W) for an additional 48 weeks on top of methotrexate. After a washout period of eight to 12 weeks, all subjects received 10mg ozoralizumab Q4W, with subsequent escalating doses dependent upon assessment, to 30mg and then 80mg Q4W. A total of 86% of subjects completed the study: 56% at 80mg, 29% at 30mg and 15% at 10mg. ACR criteria was used to measure improvement in tender or swollen joint counts and improvements in three of five other disease-activity measures, while DAS28 was used to measure the same in 28 pre-defined joints. At the completion of the study, 38% of subjects achieved clinical remission (DAS28<2.6), 32% achieved ACR70, 63% achieved at least ACR50 and 84% achieved at least ACR20. The most common adverse events were infections. Ablynx will continue to study ozoralizumab as a potential competitor to Humira.
June 11, 2012
Novartis released results from a phase III trial of ACZ885 (canakinumab) for the treatment of systemic juvenile idiopathic arthritis (SJIA). This two-part trial consisted of an open-label, single-arm active treatment period followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design period, enrolling 177 patients between ages two and 20. In part one, subjects received subcutaneous dose of ACZ885 (4mg/kg, up to 300mg) every four weeks. After eight weeks, subjects who had a minimum adapted ACR Pediatric 50 criteria began reducing their steroid use. In part two, subjects who had a minimum adapted ACR Pediatric 30 criteria at the end of part one were randomized to either continue receiving ACZ885, or to receive placebo every four weeks, until 37 flare-events had occurred. The study met its primary endpoint, with 45% of subjects able to reduce their use of steroids within 28 weeks of commencing treatment with ACZ885 (p<0.0001). Furthermore, subjects receiving ACZ885 were nearly three times (0.37 hazard ratio) less likely to suffer a new flare in part two. At the conclusion of the study, 62% of SJIA patients treated with ACZ885 had inactive disease status compared to 32% in placebo. The most common adverse events in both parts of the study were nasopharyngitis, headache and cough. Novartis is also studying ACZ885 in a phase II, open-label, multi-center study in tumor necrosis factor (TNF) receptorassociated periodic syndrome.
July 4, 2011
Nuvo Research reported results from a phase II trial of Pennsaid Viscous Solution 2% for the treatment of osteoarthritis pain. The four-week, two-arm, double-blind, vehicle-controlled, parallel, randomized trial enrolled 259 subjects who received either Pennsaid Viscous Solution 2% twice daily or a matching placebo. The primary endpoint was the reduction of pain from baseline to week four, measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The primary endpoint was reached with Pennsaid showing a greater reduction in osteoarthritis pain versus placebo (p≡0.042). The most common adverse event in both groups was application site dryness.
December 10, 2007
Pain Therapeutics and King Pharmaceuticals reported positive results from a phase III trial of Remoxy for the treatment of pain associated with osteoarthritis. This randomized, double-blinded, placebo-controlled, multi-center study enrolled four hundred and twelve subjects with osteoarthritis of the knee or hip and moderate-to-severe pain. Following a wash-out and dose titration period, the subjects received twice-daily Remoxy (10-80 mg) or matching placebo for a twelve week treatment period. The primary endpoint was defined as mean decrease in pain intensity scores between the Remoxy and placebo groups. Top-line data revealed this endpoint was reached with statistical significance (p<0.01). Secondary endpoints, including Quality of Analgesia and Global Assessment, also reached statistical significance (p<0.01). Based on the results, Pain Therapeutics and King Pharmaceuticals plan to file an NDA with the FDA in the second quarter of 2008.
February 19, 2007
Targeted Genetics released positive interim results from a phase I/II trial of tgAAC94 for the treatment of arthritis. This trial planned to enroll 120 subjects who were randomized into three dose groups to receive a single intra-articular injection of either tgAAC94 or placebo. This was followed by an open-label injection of tgAAC94 after 12 to 30 weeks, depending on when swelling in the target joint met criteria for re-injection. Treatment was safe and well tolerated in both single and repeat intra-articular injections at doses up to 1x10(13) DNase Resistant Particles per milli-liter (DRP/mL) of joint fluid in subjects with and without systemic TNF-alpha antagonists. Data observed from the first 61 subjects revealed a reduction in tenderness and swelling in the affected joint after tgAAC94 injection versus placebo. To date, 39 subjects have received a second injection. Enrollment was expected to be complete in the next few months with full results by the end of 2007.
November 21, 2005
Biogen Idec issued positive results of a phase II trial of Amevive (alefacept) for the treatment of psoriatic arthritis (PA). Amevive is currently approved to treat psoriasis. Trial results indicated that 54% of subjects receiving the drug achieved ACR20 response, vs. 23% of subjects receiving placebo (p<0.001). 17% achieved ACR50 and 7% achieved ACR70 with Amevive, vs. 10% and 2% respectively for placebo. Improvements in tender-joint (31% vs. 18%) and swollen-joint count (46% vs. 34%) were also noted. This randomized, double-blind, placebo- controlled study enrolled 185 PA patients, who received standard therapy with methotrexate plus Amevive (n=123) or placebo (n=62).
Jazz Pharmaceuticals announced positive results of a phase II trial of Xyrem (sodium oxybate) for the treatment of fibromyalgia. Xyrem is currently approved for the treatment of narcolepsy. Results from the study indicated that both the low and high dose regimens of the drug produced significant reductions in composite primary outcome variable (including Pain Visual Analog Scale, Fibromyalgia Impact Questionnaire, and Patient Global Impression of Change) compared to placebo: 34.5% in the low dose group (p=0.005) and 27.3% (p=0.048) achieved significant improvement in this measure, vs. 12.5% for placebo. Treatment was generally well tolerated. This randomized, double-blind, placebo-controlled study enrolled 188 patients, who received one of two daily doses of Xyrem (4.5g or 6g) or placebo for 8 weeks, taken in two divided doses (first at bedtime, second 2.5 to 4 hours later).
Savient issued positive results of a phase II trial of Puricase (PEG-uricase) for the treatment of refractory gout. This randomized, open label, multicenter, parallel group study enrolled 41 patients, who received one of 4 regimens of the drug (4 mg every 2 weeks, n=7; 8 mg every 2 weeks, n=8; 8 mg every 4 weeks, n=13; 12 mg every 4 weeks, n=13). The drug was shown to reduce plasma urate levels at all trial doses (from 7.56 mg/dL to 4.20; from 9.09 to 1.42; from 9.08 to 2.57; and from 8.47 to 2.60, respectively). The doses also maintained urate levels below 6 mg/dL for 73%, 92% 86% and 84% of the time. There were 5 serious adverse events reported, including gout flare (n=3), hypersensitivity reaction (n=1), and anemia (n=1).
August 1, 2005
Targeted Genetics has issued positive preliminary results of a phase I trial of tgAAC94, for the treatment of inflammatory arthritis. Trial data met their primary safety endpoint, producing a positive overall tolerability profile at doses up to 1x10(11) DRP per mL of joint volume. Secondary efficacy measures indicated that the drug produced sustained improvement in disease signs and symptoms at 4 weeks in 9 of the 11 subjects receiving the drug; this improvement was sustained in 7 of the 9 through 8 weeks. Improvements were noted for 2 of the subjects receiving placebo. This ongoing, placebo-controlled trial enrolled 15 subjects across sites in the US and Canada. Subjects received one of 2 doses of the drug (n=11) or placebo (n=4). Treatment is scheduled to continue through 24 weeks.
March 29, 2004
Genentech and XOMA reported preliminary results from a phase II trial investigating Raptiva (efalizumab), a targeted T-cell modulator for the treatment of psoriatic arthritis. Results showed the study did not reach statistical significance at 12 weeks (84 days) for the primary endpoint, ACR 20 response (20% improvement). Data demonstrated that 28% of Raptiva subjects achieved an ACR 20 response compared with 19% receiving placebo. Statistically significant Psoriasis Area and Severity Index results were found among a subgroup of subjects with moderate-to-severe plaque psoriasis. The randomized, placebo-controlled study enrolled 107 subjects with psoriatic arthritis.
March 15, 2004
The University of Hong Kong reported positive results from a trial investigating Lyprinol, a marine lipid extract for the treatment of osteoarthritis. Results showed a greater improvement in the perception of pain as measured by a 100-mm visual analog scale (VAS). In addition, subjects who took Lyprinol had improved scores in the physical function and psychological status domains from week four. The randomized, placebo-controlled study enrolled 80 subjects with knee OA. Subjects received either Lyprinol or placebo for six months and were allowed paracetamol/acetaminophen rescue treatment during the study. The trial was conducted from 2001-2003 at the Queen Mary Hospital of the University of Hong Kong.
October 20, 2003
Pain Therapeutics reported positive results from a phase II trial investigating Oxytrex, a narcotic painkiller for the treatment of osteoarthritis pain. Results demonstrated that Oxytrex achieved a statistically significant result in reducing pain intensity during the 21-day treatment period against oxycodone, the studies primary endpoint. In addition, data showed that Oxytrex achieved a statistically significant result in both the qualities of analgesia and global assessment compared to the placebo group. Oxytrex was well tolerated with no reports of serious adverse events. The randomized, double-blinded, placebo-controlled study enrolled 350 subjects at 30 sites across the U.S. The study was designed to evaluate the safety and efficacy of Oxytrex relative to oxycodone and placebo over a three-week treatment period.
March 4, 2003
Medinox reported positive results from a phase I trial investigating MX-1094, a Non-Steroidal Anti-Inflammatory Drug (NSAID) for the treatment of arthritis. Results showed the drug was well tolerated and exhibited the desired pharmacokinetic profile when compared to the alternative treatment naproxen. The randomized, double blind, placebo-controlled, dose escalating study enrolled 48 healthy volunteers and was designed to evaluate the safety, tolerability and pharmacokinetics of MX-1094. Medinox plans to conduct additional trials to assess the gastrointestinal safety of the drug.
February 25, 2002
An analysis of placebo-controlled data indicates that European studies of ML-3000 did not meet all of the efficacy endpoints required by the FDA. The European trials, which were conducted by Merckle GmbH, were part of a global development program consisting of both United States and European Union clinical trials. A United States safety and efficacy study is under way and expected to be completed during the next twelve months. If the ongoing trial meets the required efficacy endpoints, additional efficacy studies will be initiated in order to support a potential NDA submission. ML-3000 is being co-developed by Forest Laboratories and Merckle GmbH for the treatment of osteoarthritis.