Skip Navigation

Advertise|Press|Contact|FAQ|CWConnect

Bookmark/Print/Share

Home » Drug Information » New Medical Therapies™

Rheumatoid Arthritis

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%.

November 11, 2013

Vertex Pharmaceuticals released results of a phase IIb study of VX-509 for the treatment of active rheumatoid arthritis (RA) in patients taking methotrexate. The double-blind, randomized, placebo-controlled, 24-week phase IIb study enrolled 358 people with RA who had active disease despite methotrexate treatment. Patients were randomized to receive placebo or one of four doses of VX-509 (100mg once daily, 150mg once daily, 200mg once daily or 100mg twice daily) for 24 weeks. The study met its primary endpoints of both the proportion of people who achieved at least a 20% improvement in signs and symptoms of RA, as measured by the ACR improvement criteria (ACR20), and the change from baseline in Disease Activity Score for 28 joints (DAS28). All doses of VX-509 showed statistically significant ACR20 and ACR50 responses v. placebo and statistically significant improvement from baseline in DAS28 v. placebo. The three highest dose groups showed ACR20 responses of between 58% and 68%, compared to 18% for placebo, and statistically significant ACR70 responses v. placebo. The discontinuation rate due to adverse events was 6.6% for the pooled VX-509 treatment group and 8.5% for the placebo group. Overall, adverse event rates were 51.2% in the pooled VX-509 treatment groups compared to 38% for those who received placebo, and the majority of adverse events observed in the study were mild to moderate.

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 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.

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.

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

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.

November 28, 2011

Galapagos N.V reported results from a phase II trial of GLPG0634 for the treatment of rheumatoid arthritis. This trial enrolled 36 subjects with moderate to severe active rheumatoid arthritis showing an insufficient response to the standard-of-care treatment, methotrexate. The subjects received placebo or GLPG0634 administered in two dosage arms of 200 mg: one arm taking a once-daily dose and the other taking twice-daily doses of 100 mg, both with continued background therapy of MTX. The treatment duration was four weeks. The primary endpoint was the ACR20 response rate at Week 12. For the GLPG0634 treatment groups combined, 83% of subjects showed improvement in ACR20 score versus 33% on placebo (p≡0.0067). The secondary endpoints of ACR50 and ACR70 were also achieved. Significant improvements were observed on the Disease Activity Score (DAS28) and C-reactive protein (CRP) measurements compared to placebo (p<0.0001). GLPG0634 was well-tolerated and all subjects completed the trial.

October 31, 2011

Neovacs issued interim results from a phase IIa trial of TNF-Kinoid for the treatment of rheumatoid arthritis. This double-blind, randomized, placebo-controlled study, TNF-K-003, enrolled 40 subjects. These data are from the first 24 subjects who received the first two dose levels of the TNF-Kinoid: 90mcg, 180mcg or placebo. The immune response data measured at two months was positive: 50% of the subjects at the 90mcg dose and 80% of the subjects at the 180mcg dose developed antibodies to TNF. In the 11 subjects who developed measurable antibodies to TNF up to day 84, 55% saw a decline of at least 20% in their ACR score (ACR20), versus 20% in the group of 10 subjects without antibody to TNF. In addition, the average level of CRP fell by 42% in subjects who developed antibodies to TNF, versus an increase of 12% in subjects without anti-TNF antibodies.

September 12, 2011

Vertex released results from a phase IIa trial of VX-509 for rheumatoid arthritis. This double-blind, randomized, placebo-controlled study enrolled 204 subjects with active moderate to severe rheumatoid arthritis who received four dose levels of VX-509 or placebo twice daily for 12 weeks. The study met its two primary endpoints: the proportion of subjects who achieved at least a 20 percent improvement in the signs and symptoms of rheumatoid arthritis (ACR20) at week 12 and the change from baseline in Disease Activity Score 28 (DAS28) at week 12. The two highest doses (100 mg and 150 mg) showed statistically significant ACR20 response rates of 81% and 82% , respectively. compared to 41% for placebo. In these same dose arms, 35% and 37%, respectively, achieved DAS28 remission compared to 7% in the placebo arm.

July 18, 2011

Sanofi and Regeneron Pharmaceuticals released interim results from a phase IIb/III trial of sarilumab for rheumatoid arthritis. This randomized, double-blind, placebo-controlled study MOBILITY, enrolled 306 subjects who received sarilumab 100 and 150 mg every week and 100 mg, 150 mg and 200 mg every other week, or matching placebo, both in addition to methotrexate. The primary endpoint was the proportion of patients achieving at least a 20% improvement in RA symptoms (ACR20) after 12 weeks. This endpoint was reached by 49% of subjects receiving the lowest sarilumab dose regimen and 72% of subjects receiving the highest dose regimen compared to 46.2% of subjects receiving placebo. Sarilumab also demonstrated significant benefit compared to placebo in secondary endpoints, including ACR 50, ACR 70, and DAS 28 scores.

May 30, 2011

Centocor Ortho Biotec released interim results from the first part of a phase II trial of sirukumab for rheumatoid arthritis. This two-part, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial enrolled subjects with active rheumatoid arthritis despite methotrexate therapy. In Part A, approximately 40 subjects were randomly assigned to receive either sirukumab 100 mg or placebo subcutaneous (SC) injections at week zero and every two weeks thereafter through week ten. At week 12, subjects randomized to sirukumab began receiving placebo and subjects randomized to placebo began receiving sirukumab 100 mg SC injections every two weeks through week 22. An interim analysis was performed when all subjects randomized in Part A had either completed the week 12 visit or terminated study participation. The primary endpoint of Part A was the reduction in Disease Activity Score 28 (DAS28 CRP) at week 12. The interim analysis showed 82% of subjects in the sirukumab group achieved good or moderate DAS28 CRP response (38% good and 44% moderate) compared with 32% (11% good and 21% moderate) of subjects receiving placebo (P≡0.015). By week 12, ACR20 (at least a 20 percent improvement in American College of Rheumatology Scores) was seen in 75% of the sirukumab-treated arm compared with 21% of the placebo arm (P≡0.002). Sirukumab was generally well-tolerated through ten weeks of treatment.

May 23, 2011

Pfizer issued results from a phase II trial of ozoralizumab for the treatment of rheumatoid arthritis. This trial enrolled 253 subjects with active rheumatoid arthritis on a stable background therapy of methotrexate. The subjects were randomly assigned to four subcutaneous injections of ozoralizumab in five dose groups (10mg, 30mg, 80mg every four weeks; 10mg, 80mg every eight weeks) or four subcutaneous injections of placebo every four weeks. The trial met the primary efficacy endpoint, with the highest dose of ozoralizumab (80 mg every four weeks) resulting in a statistically significant improvement of ACR20 responses compared with placebo at week 16. This dose level also showed an improvement over placebo for secondary endpoints, including improvements of clinical scores, DAS28, ACR50, ACR70 and EULAR response at week 16. No dose limiting toxicities were observed.

May 9, 2011

Pfizer released results from two phase III trials of tofacitinib for moderate-to-severe rheumatoid arthritis (RA). ORAL Standard was a 12 month study and enrolled 717 who had an inadequate response to MTX. The subjects received either tofacitinib 5 or 10 mg twice daily, adalimumab (standard of care) 40 mg subcutaneously every other week or placebo, each added to stable background MTX. At the month-three visit, non-responders in the placebo cohort converted to tofacitinib (5 or 10 mg) for the remainder of the study. At the end of six months, the entire placebo cohort converted to tofacitinib. ORAL Step was a six month study and enrolled 399 subjects who had an inadequate response to at least one TNF inhibitor. The subjects received tofacitinib 5 or 10 mg twice daily or placebo, both added to stable background MTX. At the month-three visit, the placebo cohort converted to tofacitinib for the remainder of the study. In both trials, all primary endpoints were reached at both doses. Data showed statistically significant changes versus placebo in reducing signs and symptoms of RA, as measured by ACR20 response rates; in improving physical function, as measured by mean change in HAQ DI; and in reaching DAS28-4(ESR) <2.6 measured at six and three months, respectively.

March 14, 2011

Pfizer reported initial results from a phase III trial of tofacitinib for the treatment of rheumatoid arthritis. This randomized, double blind, placebo controlled study, ORAL Sync, enrolled approximately 700 subjects with moderately to severely active RA who had a previous inadequate response to a DMARD. The subjects received tofacitinib doses 5 mg and 10 mg given twice daily or placebo in addition to background traditional DMARD therapy. The primary endpoints were reached with statistical significance versus placebo in reducing signs and symptoms of rheumatoid arthritis, as measured by ACR20 response rates at six months; in improving physical function, as measured by mean change in HAQ DI at three months; and in reaching DAS28-4(ESR) <2.6 at six months. The safety profile was consistent with previous studies.

December 20, 2010

Lexicon released results from a phase II trial of LX2931 for the treatment of rheumatoid arthritis. This randomized, double-blind, placebo-controlled study enrolled 208 subjects on stable methotrexate therapy in the US and Eastern Europe. The subjects received a 70 mg, 110 mg or 150 mg dose once daily for 12 weeks. The primary endpoint was ACR20 (American College of Rheumatology- 20 percent improvement in symptoms associated with rheumatoid arthritis) at 12 weeks. Data demonstrated that subjects treated with the 150 mg dose showed an improvement in ACR20 response at week 12 (60% versus 49% for placebo). Those treated with 70 mg or 110 mg once daily did not indicate improvement in the ACR20 at week 12 (44% and 41% response rates, respectively) relative to placebo. Adverse events were mild-to-moderate.

November 15, 2010

Pfizer reported positive results from a phase III trial of tasocitinib for the treatment of rheumatoid arthritis (RA). This six-month, double-blind, placebo-controlled study, ORAL Solo (1045), enrolled 611 subjects with moderately to severely active RA who had an inadequate response to at least one disease- modifying anti-rheumatic drug. The subjects were randomized to tasocitinib 5 mg or 10 mg or placebo twice a day. After three months of treatment, subjects randomized to placebo began receiving tasocitinib 5 mg or 10 mg in a blinded manner. Primary efficacy endpoints were ACR20 response rates (20 percent improvement from baseline in the American College of Rheumatology scale), mean change in HAQ-DI (Health Assessment Questionnaire Disability Index) and DAS (Disease Activity Score) 28 (DAS28) <2.6, all at month three. Two of the endpoints, ACR20 response rates and mean change in HAQ-DI, demonstrated statistically significant reductions versus placebo at three months (p<0.0001). The third primary endpoint, DAS28, resulted in a numerically greater, but not statistically significant difference from placebo. A similar frequency of adverse events was seen across all treatment groups.

May 17, 2010

Incyte and Eli Lilly released positive results from an ongoing phase II study evaluating INCB28050 for the treatment of rheumatoid arthritis. This 6-month, dose ranging study enrolled 125 subjects with rheumatoid arthritis who were inadequately controlled by any disease modifying anti-rheumatic drug therapy. The subjects received once daily doses of INCB28050 (4 mg, 7 mg and 10 mg). These data are from three months of therapy. American College of Rheumatology (ACR) scores (ACR20, 50 and 70), representing the percentage of improvement at 12 weeks of treatment with INCB28050, included response rates up to 60%, 36% and 16%, respectively. ACR20, 50 and 70 scores for placebo treated patients were 32%, 13% and 3%, respectively. All doses of INCB28050 were well-tolerated.

December 7, 2009

OxyPharma reported positive preliminary results from a phase II trial of Rabeximod for the treatment of rheumatoid arthritis. This international randomized, four armed, double-blind, placebo-controlled trial enrolled 224 subjects with moderate to severe rheumatoid arthritis that was not responsive to prior treatment with methotrexate. The subjects received Rabeximod (6.25 mg, 15 mg, or 37.5 mg once daily) or placebo, along with stable doses of methotrexate, for 12 weeks. The primary endpoint, therapeutic efficacy based on the ACR20 response rate at 12 weeks, was not reached. None of the treatment groups demonstrated a significant effect at this time-point. However, Rabeximod did have a delayed onset of action, which resulted in a significant therapeutic effect of the dosing regimen at 16 weeks. At 16 weeks, the 15 mg Rabeximod dose group exhibited statistically significant (p<0.05) effects for seven of the key secondary endpoints of treatment: ACR20, DAS28 response rate, pain, subject global assessment, physician global assessment, number of swollen joints and number of tender joints. Rabeximod was well tolerated and the incidence of adverse events in the Rabeximod and placebo groups was similar.

September 14, 2009

Nitec Pharma issued positive results from a phase III trial of Lodotra for the treatment of rheumatoid arthritis. This 12-week, multi-center, double-blind study, dubbed CAPRA-2 (Circadian Administration of Prednisone in Rheumatoid Arthritis-2), enrolled 350 subjects, all of whom were inadequate responders to DMARD therapy. The subjects were randomized to receive either Lodotra 5mg once daily or placebo in addition to their existing therapy. The primary efficacy endpoint was the ACR-20 response rate, defined as at least a 20% improvement in a number of disease-specific criteria. The Lodotra treatment arm showed an ACR-20 response of 49% compared to 29% in the placebo group (p≡0.0002). The reduction of morning stiffness, a key secondary endpoint, was 44% in the Lodotra group and 21 % in the placebo group (p≡0.0008). Lodotra was safe and well tolerated. The number of adverse events was comparable in both groups.

August 3, 2009

Genmab and GlaxoSmithKline released positive results from a phase III trial of ofatumumab for the treatment of rheumatoid arthritis. This 24 week double-blind study enrolled 260 subjects who had an inadequate response to methotrexate therapy across Europe, South America and Australia. The subjects were randomized to receive two 700 mg doses of intravenous ofatumumab or placebo two weeks apart, in addition to background methotrexate. Disease status was measured every four weeks. The primary endpoint was ACR20 at 24 weeks, defined as a 20 percent or greater improvement from baseline on the American College of Rheumatology Criteria. The ACR20 response rate was significantly greater for the subjects receiving ofatumumab than those on placebo, with a 50% response rate in the ofatumumab arm compared to 27% for the placebo arm (p<0.001). All key secondary endpoints were also significant (p<0.001). Treatment was generally well tolerated.

July 27, 2009

Rigel released positive results from a phase II trial of R788 for the treatment of rheumatoid arthritis. This 6 month, multi-center, randomized, double blind, placebo controlled, parallel dose study, dubbed TASKi2, enrolled 457 subjects who had failed to respond to methotrexate alone. The subjects received R788 100 mg twice daily (BID) or 150 mg once daily (QD) or placebo, along with stable a dose of methotrexate. The primary endpoint was to measure the efficacy of R788 as determined by ACR20 scores at the end of 6 months. ACR20 was reached by 66% of subjects in the 100mg BID dose arm and 57% of subjects in the 150mg Qd arm, compared to 35% in the placebo arm (p<0.001). Both R788 dose groups reported higher ACR 50, ACR 70 and DAS28 response rates than the placebo group and statistical significance was reached for all measures in the 100mg BID treatment arm. R788 was generally safe and well tolerated.

March 23, 2009

Chelsea Therapeutics reported positive results from a phase II trial of CH-1504 for the treatment of rheumatoid arthritis. This 12-week, multi-national, double blind, 4-arm, parallel group study enrolled 201 methotrexate (MTX) naive subjects. The subjects received CH-1504 (0.25mg, 0.50mg or 1.00mg once daily oral doses) or MTX (20.00mg once weekly oral dose). The trial included a 12-week treatment period and 4-week follow-up period. The primary endpoint was the percentage of subjects with an ACR 20 response, defined as at least a 20% improvement in the signs and symptoms of rheumatoid arthritis, at the end of 12 weeks. The primary endpoint was reached. In addition, all doses of CH-1504 showed comparable ACR50 and ACR70 response rates to the standard oral dose of methotrexate administered once weekly. All doses of CH-1504 show a clinically relevant decrease in ALT elevations compared to methotrexate and the efficacy of CH-1504 was associated with reduced hepatotoxicty compared to the MTX. CH-1504 was safe and well tolerated at all dose levels and adverse events were generally mild.

January 12, 2009

Genentech and Biogen released positive results from a phase III trial of MabThera for the treatment of rheumatoid arthritis (RA). This randomized, controlled, double-blind, parallel-group study, dubbed IMAGE, enrolled 755 methotrexate (MTX)-nave patients with active RA across several international sites. The subjects received either MabThera (500mg or the currently approved 1000mg dose) or placebo by intravenous infusion on days one and 15, in combination with newly initiated MTX. The subjects who were not in DAS28-ESR (disease activity score-erythrocyte sedimentation rate) remission at week 24 received a second course of MabThera at the same dose as the first course. The primary endpoint was change in total Genant-modified total Sharp scores measured at week 52. Following one year of treatment, MabThera 1000 mg in combination with MTX exhibited a significant reduction in the rate of progressive joint damage, compared to treatment with MTX alone. Both doses of MabThera in combination with MTX were superior to MTX alone in relieving the signs and symptoms of RA. Based on the results, further development is planned.

November 10, 2008

Roche reported positive results from a phase III trial of Actemra for the treatment of rheumatoid arthritis. This three-arm, randomized, double-blind, placebo- controlled study, dubbed LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage), enrolled 1,196 subjects across several international sites. The subjects received Actemra (4 mg/kg or 8 mg/kg) or placebo via intravenous infusion every four weeks plus methotrexate or placebo plus methotrexate weekly. Response to treatment (analyzed by measuring structural damage in the joints), disease activity, measured by the American College of Rheumatology (ACR) score and improvement in physical function were all assessed. The mean change in the combined Genant-modified Sharp score , which assesses progression of both joint erosion and joint space narrowing, was lower among both Actemra arms compared to the placebo arm (0.3, 0.3 versus 1.1, respectively; p<0.001). In addition, the study showed that 85% and 81% of subjects treated with Actemra (8 mg/kg or 4 mg/kg, respectively) experienced no progression of either joint erosion or joint space narrowing, compared with 67% of subjects treated with placebo plus methotrexate. In addition, at one year of treatment, 56%, 36% and 20% of subjects treated with Actemra 8 mg/kg plus methotrexate achieved ACR20, ACR50 and ACR70, respectively, and 47%, 29% and 16% of subjects in the Actemra 4 mg/kg arm achieved these ACR scores, respectively. In contrast, 25%, 10% and 4% of subjects in the control group achieved ACR20, ACR50 and ACR702, respectively. Disease remission (DAS28 <2.6) was demonstrated in 47% and 30% of the Actemra 8 mg/kg and 4 mg/kg arms, respectively, compared with 8% of the placebo arm.

Roche reported positive results from a phase III trial of Actemra for the treatment of rheumatoid arthritis. This three-arm, randomized, double-blind, placebo- controlled study, dubbed LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage), enrolled 1,196 subjects across several international sites. The subjects received Actemra (4 mg/kg or 8 mg/kg) or placebo via intravenous infusion every four weeks plus methotrexate or placebo plus methotrexate weekly. Response to treatment (analyzed by measuring structural damage in the joints), disease activity, measured by the American College of Rheumatology (ACR) score and improvement in physical function were all assessed. The mean change in the combined Genant-modified Sharp score , which assesses progression of both joint erosion and joint space narrowing, was lower among both Actemra arms compared to the placebo arm (0.3, 0.3 versus 1.1, respectively; p<0.001). In addition, the study showed that 85% and 81% of subjects treated with Actemra (8 mg/kg or 4 mg/kg, respectively) experienced no progression of either joint erosion or joint space narrowing, compared with 67% of subjects treated with placebo plus methotrexate. In addition, at one year of treatment, 56%, 36% and 20% of subjects treated with Actemra 8 mg/kg plus methotrexate achieved ACR20, ACR50 and ACR70, respectively, and 47%, 29% and 16% of subjects in the Actemra 4 mg/kg arm achieved these ACR scores, respectively. In contrast, 25%, 10% and 4% of subjects in the control group achieved ACR20, ACR50 and ACR702, respectively. Disease remission (DAS28 <2.6) was demonstrated in 47% and 30% of the Actemra 8 mg/kg and 4 mg/kg arms, respectively, compared with 8% of the placebo arm. A BLA and an MAA are currently under review by the FDA and EMEA, respectively.

October 20, 2008

Biogen released negative results from two phase II trials of baminercept for the treatment of rheumatoid arthritis. The first study was a randomized, double-blind, placebo-controlled, multicenter, dose-finding design. It enrolled 380 subjects with active RA who had an inadequate response to conventional DMARD therapy. The study was designed to assess the efficacy of five different regimens of baminercept when administered over 12 weeks in combination with methotrexate. The second study was a randomized, double-blind, placebo-controlled, multicenter design. This study had planned to enroll 120 subjects with active RA who had an inadequate response to TNF inhibitors. It was designed to assess the efficacy of 200 mg dose of baminercept administered over 12 weeks in combination with methotrexate. The primary endpoint of both studies was the proportion of subjects who achieved an ACR50 response, defined as a 50% improvement compared to baseline for swollen and tender joint counts and other clinical measures, at week 14. Secondary endpoints included the proportion of subjects to achieve scores of ACR20 and ACR70, improvement in DAS scores and improvements in Quality of Life. Neither the primary nor secondary endpoints were reached in the studies. Based on the results, Biogen decided to discontinue the development of baminercept for rheumatoid arthritis.

June 30, 2008

MediGene released positive results from a phase IIa trial of RhuDex for the treatment of rheumatoid arthritis. This two-week placebo-controlled study enrolled 29 subjects with rheumatoid arthritis on standard methotrexate therapy. The study was designed to examine the tolerability and oral availability of RhuDex. Following an increase of the plasma level after treatment with 100 and 200 mgs of RhuDex, a saturation of the plasma concentration was reached with a 400 mg dose. RhuDex was well tolerated at all dosages administered. In addition, no interaction between RhuDex and methotrexate was observed. Based on the results, phase II trials are planned for 2009.

June 23, 2008

Incyte released positive results from a phase IIa trial of INCB18424 for the treatment of rheumatoid arthritis (RA). This 28-day, double-blind, placebo-controlled study enrolled 48 subjects with active RA. Results are from the first of four treatment groups, involving 16 subjects who received INCB18424 at a dose of 15 mg twice-daily or placebo. Assessments were conducted at weeks one, two and four. The primary endpoints were safety, American College of Rheumatology (ACR) 20, ACR50, ACR70 scores and Disease Activity Score (DAS 28). Treatment with INCB18424 led to ACR20/50/70/90 response rates of 75%/50%/25%/17%, respectively, with responses seen as early as one week. The mean DAS28 score at baseline was 6.18, indicating active disease. After 28 days of treatment with INCB18424, 50% of the subjects achieved DAS28 less than 3.2 indicating minimal disease activity, and 25% achieved DAS28 less than 2.6 indicating a score consistent with complete remission if sustained. Treatment was generally well tolerated, with no serious adverse events reported. Three additional treatment groups involving 32 subjects are currently being evaluated at INCN18424 5 and 25 mg twice-daily doses and a 50 mg once-daily dose.

June 16, 2008

Schering-Plough and Centocor released positive results from a phase III trial of golimumab for the treatment of rheumatoid arthritis (RA). This multi-center, double-blind trial, dubbed GO-AFTER (GOlimumab After Former anti-TNF Therapy Evaluated in RA), enrolled 461 subjects with active RA. The subjects received placebo, golimumab 50 mg or golimumab 100 mg all via subcutaneous injection, along with any stable therapy, every four weeks for 24 weeks. The primary endpoint was at least 20 percent improvement in arthritis symptoms (ACR 20) at week 14. This endpoint was reached by 35% and 38% of subjects receiving golimumab 50 mg and 100 mg, respectively, compared to 18% of subjects receiving placebo (p<0.001). These results were maintained through six months. Among the 58 percent of subjects whose prior anti-TNF-alpha therapy had been discontinued due to lack of efficacy, 36% receiving golimumab 50 mg and 43% receiving golimumab 100 mg achieved ACR 20 as compared to 18% of subjects treated with placebo (p=0.006 for 50 mg group; p<0.001 for 100 mg group, respectively). Improvements were also seen in physical function and disease activity through six months as measured by the Health Assessment Questionnaire (HAQ) and the Disease Activity Score (DAS28), respectively. In the combined golimumab dosing group, 52% of subjects experienced a clinically relevant improvement in physical function, compared with 34% of subjects receiving placebo (p<0.001). More than half of subjects in the combined golimumab group were classified as DAS28 responders (using either C-reactive protein or erythrocyte sedimentation rate), compared with 23% and 25% of the placebo-treated group, respectively. Treatment was generally well tolerated. An MAA is currently under review by the EMEA.

May 19, 2008

Roche issued positive results from an ongoing phase III trial of Actemra for the treatment of rheumatoid arthritis. This three-arm, randomized, double-blind, placebo- controlled study, dubbed LITHE (TociLIzumab Safety and THE Prevention of Structural Joint Damage), enrolled 1,196 subjects across several international sites. The subjects received Actemra (4 mg/kg or 8 mg/kg) or placebo administered via intravenous infusion every four weeks combined with methotrexate weekly. Response to treatment was analyzed by measuring structural damage in the joints through X-rays. Disease activity, measured by the ACR (American College of Rheumatology) score and improvement in physical function, measured through the Health Assessment Questionnaire (HAQ) were also assessed. The one-year data showed that a greater proportion of subjects treated with Actemra plus methotrexate versus placebo plus methotrexate over 52 weeks achieved a significant reduction in the progression of structural joint damage. Actemra also reduced disease signs and symptoms at one year. Treatment was well tolerated. Full results from this study are expected in 2009. A BLA is for Actemra is currently under review by the FDA.

Savient released positive interim results from an ongoing open label extension trial of Puricase for the treatment of gout. This study enrolled 82 subjects with treatment-failure gout who had completed previous phase III trials with Puricase. Of these 82 subjects, half received Puricase 8 mg every two weeks and half received Puricase every four weeks. Continued normalization of plasma uric acid (PUA) was seen in 100% and 70% of subjects who had normalized PUA during the original phase III trials in the two- and four-week dosing groups, respectively. Approximately 25% of subjects who did not have PUA responses during the original trials attained PUA normalization in the study with nine months or more of continuous Puricase treatment either every two or four weeks. Of the non-responders for the resolution of gout tophi in the previous studies, 31% showed a complete response in this study with additional subjects showing a partial response for tophus resolution. No incidence of gout flares was reported in the two-week arm after five months. Infusion reactions were reported by 21% of subjects, which was comparable to that reported during the original trials. Savient plans to submit a BLA to the FDA in September of 2008.

February 4, 2008

Roche issued positive results from a phase III trial of MabThera as a first-line therapy for rheumatoid arthritis. This international, randomized, placebo controlled, double blind, parallel group study was dubbed SERENE (Study Evaluating Rituximabs Efficacy in methotrexate iNadequate rEsponders). The trial enrolled five hundred and nine subjects who received either MabThera (500 mg or 1000 mg) or placebo by intravenous infusion on days one and fifteen, plus weekly methotrexate (MTX). The primary endpoint was the percentage of subjects who had at least a 20% reduction in a number of symptoms and measures of disease, measured via the American College of Rheumatology assessment (ACR20) at week twenty four. The primary endpoint was reached; a significantly greater proportion of subjects treated with MabThera/MTX achieved an improvement in disease signs and symptoms compared to those treated with MTX alone. Treatment was well tolerated, with a profile consistent with previous studies. Based on the results, Roche intends to file for approval of MabThera as a first-line therapy.

December 10, 2007

4SC issued positive preliminary results from a phase IIa trial of SC12267 for the treatment of rheumatoid arthritis. This randomized, double-blind study enrolled 120 subjects in Germany, Poland and Siberia. The subjects received 20 mg or 35 mg of oral SC-12267, or placebo for 12 weeks. The primary endpoints were improvements on the Disease Activity Score (DAS28) and American College of Rheumatology (ACR) scores, with improvements of at least 20% (ACR20), 50% (ACR50) and 70% (ACR70). Significant results were seen in a subgroup of subjects who had received disease modifying anti-rheumatic drugs prior to the trial. A reduction in the DAS28 score of 0.94 and 1.50 was seen in 20 and 35 mg-treated arms, respectively, compared with 0.69 in the placebo arm. An ACR20 response was seen in 25%, 50% and 13%, ACR50 was observed in 0%, 20% and 6.7% and ACR70 was observed in 0%, 20% and 0% of the 20 mg, 35 mg and placebo arms, respectively. Based on the results, 4SC plans to move forward with the development of SC12267.

July 30, 2007

Roche released positive results from a phase III trial of Acterma for the treatment of rheumatoid arthritis. This two-arm, randomized, double-blind, placebo-controlled study, dubbed AMBITION (Acterma versus Methotrexate double-Blind Investigative Trial In mONotherapy), enrolled 673 subjects internationally. Subjects received either Acterma intravenously (8 mg/kg) every four weeks plus placebo capsules weekly or placebo infusions every four weeks plus methotrexate weekly. The primary endpoint of non-inferiority was achieved. Results showed a greater proportion of subjects treated with Acterma (8mg/kg), achieved a significant improvement in disease signs and symptoms, based on American College of Rheumatology (ACR) scores, following 24 weeks of treatment, compared to subjects treated with methotrexate alone. Roche plans to file for US approval later in 2007.

July 23, 2007

Can-Fite reported mixed results from a phase IIb trial of CF-101 for the treatment of rheumatoid arthritis. This double-blind, placebo controlled trial enrolled 239 subjects internationally. Subjects received CF-101 (0.1, 1 or 4 mg) twice daily or placebo, both in combination with weekly methotrexate (MTX). The primary endpoint was an American College of Rheumatology score of 20 (ACR20) at week 12, defined as at least a 20% improvement in symptoms. Secondary endpoints included ACR50, ACR70 and European League Against Rheumatism (EULAR) response measures. The ACR20 response showed no difference between the two treatment groups, with a response rate of about 50% in both arms. However, differences were seen in the ACR50 responses, with rates in the CF-101 arm of 20%, 27% and 19% in the 0.1, 1 and 4 mg groups, respectively, as compared to 13% in the placebo arm. Statistical significance was reached in the CF-101 (1 mg) arm versus placebo (p=0.04). The EULAR response rates were 6%, 18% and 11% in the 0.1, 1 and 4 mg groups as compared to 5% of the placebo group. Again, the CF101 1mg group showed statistical significance compared to placebo (p=0.04). Based on the results, Can-Fite plans to advance the 1 mg dose of CF-101 into future trials.

July 16, 2007

Roche announced positive results from a phase III trial of Acterma for the treatment of rheumatoid arthritis. This three-arm, randomized, double-blind, placebo-controlled study, dubbed RADIATE (RheumAtoiD ArthritIs Study in Anti-TNF FailurEs), enrolled 498 subjects internationally. Subjects received either Acterma intravenously (4 mg/kg or 8 mg/kg) every four weeks plus methotrexate weekly or placebo infusions every four weeks plus methotrexate weekly, for 24 weeks. The primary endpoint was response to treatment based on the American College of Rheumatology (ACR) score; DAS28, a measurement of disease activity, and EULAR response criteria, a measurement of treatment response. The primary endpoint was achieved, with a significant reduction in each primary endpoint when compared to placebo. Treatment with Acterma was generally well tolerated. Acterma is currently undergoing several additional phase III trials.

June 25, 2007

Chugai reported positive results from a phase III trial of Acterma for the treatment of rheumatoid arthritis. This trial, dubbed OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate responders), was a randomized, double-blind study which enrolled 623 subjects with moderate to severe rheumatoid arthritis (RA). Subjects received Actemra intravenously (either 4mg/kg or 8mg/kg) every 4 weeks plus methotrexate weekly or placebo infusions plus methotrexate weekly, for six months. The primary endpoint was achieved, with a significant reduction in the signs and symptoms of RA in the Acterma group versus placebo over six months. In the Acterma (8mg/kg) and methotrexate arm, 58.5% of the subjects achieved at least a 20% improvement (ACR20) in RA symptoms compared with 26.5% of subjects receiving placebo plus methotrexate after 24 weeks. In this same Acterma treatment group, 43.9% of subjects achieved at least a 50% (ACR50) reduction in symptoms compared to 10.8% of subjects receiving placebo and ACR70 was achieved in 22% of the treatment group versus 2% in the control group. Disease remission was measured utilizing the Disease Activity Score index (DAS28). At 24 weeks, the difference in the reduction of DAS28 from baseline was greater and statistically significant (p<0.0001) in subjects treated with Acterma 8mg/kg plus methotrexate (-3.43) compared to those in the placebo and methotrexate group (-1.55). Several additional phase III trials of Acterma are currently underway.

June 11, 2007

Roche released positive results from a phase III trial of Acterma for the treatment of rheumatoid arthritis. This international, two-arm, randomized, double-blind study was dubbed TOWARD (Tocilizumab in cOmbination With traditional DMARD therapy). The trial enrolled 1,216 subjects who received either 8mg/kg Actemra intravenously every 4 weeks or placebo, in combination with traditional disease modifying drugs (DMARDs). At the end of the treatment period, symptoms were measured using the standard American College of Rheumatology (ACR) score assessment method. Results revealed that the subjects who received Actemra in combination DMARDs achieved a significant improvement in disease signs and symptoms at week 24, compared to those treated with DMARDs alone. Further results are expected to be released in the coming months. Three additional phase III trials of Acterma are currently underway.

March 5, 2007

UCB released positive results from two phase III trials of Cimzia for the treatment of rheumatoid arthritis. The first trial, RAPID 1, enrolled 992 subjects who were randomized to receive one of three treatment regimens: 400mg Cimzia at the start of the study and at weeks two and four, then 200mg given every two weeks with methotrexate; 400mg Cimzia every two weeks with methotrexate or placebo every two weeks with methotrexate. The second trial, RAPID 2, enrolled 634 subjects who were also randomized to one of three treatment groups: 400mg liquid Cimzia at the start of the study and at weeks two and four, then 200mg given every two weeks with methotrexate; 400mg liquid Cimzia every two weeks with methotrexate or placebo every two weeks with methotrexate. In all arms of both studies the dose of methotrexate was 10mg per week or greater. Treatment was well tolerated, with no unexpected adverse events. Both trials achieved the primary endpoint with the American College of Rheumatology responder rate (ACR 20) at week 24 reaching statistical significance in both Cimzia treated arms when compared to the placebo treated arm (p<0.001). In addition, the co-primary endpoint in the RAPID 1 arm was also met, with a statistically significantly smaller change from baseline in modified Total Sharp Score (mTSS) observed at week 52 in both Cimzia treatment arms compared with the placebo treated arm (p<0.001). Based on these results, a submission is planned in the U.S. for the treatment of rheumatoid arthritis during the second half of 2007.

February 12, 2007

Opexa Rheumatology reported positive results from a phase II trial of Tovaxin for the treatment of rheumatoid arthritis. This open label trial, conducted at the Shanghai Institutes of Biological Sciences in China, enrolled 15 subjects who received Tovaxin via six subcutaneous injections over 12 months. Treatment was well tolerated. Tovaxin also resulted in T-cell regulatory immune responses which collectively led to substantial clinical improvements, measured using the American College of Rheumatology (ACR) guidelines. Improvements in joint swelling were observed for ACR 20 (73.3%), ACR 50 (67.7%) and ACR 70 (55.3%), with a significant overall reduction in swollen and tender joints (p less than 0.01). In addition, there was a significant reduction from baseline in serum markers of inflammation, including erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor (p less than 0.05). Based on the results, Opexa plans to commence development of Tovaxin for the treatment of rheumatoid arthritis in the United States.

December 4, 2006

Phytomedics issued positive results from a phase II trial of PMI-001 for the treatment of rheumatoid arthritis. This randomized, double-blinded, active treatment-controlled trial enrolled 121 subjects who received PMI-001 or Sulfasalazine for six months. The primary endpoint was the proportion of PMI-001 subjects who achieved an American College of Rheumatology (ACR20) response at the end of the trial in comparison to the proportion of sulfasalazine-treated subjects. By the trial’s conclusion, 53.3% of subjects in the PMI-001 treatment group achieved an ACR20 response compared to 21.3% in the sulfasalazine group. In addition, 36.7% of the subjects in the PMI-001 treatment group reached ACR50 and 26.7% reached ACR70 versus 3.3% and 3.3%, respectively, for the Sulfasalazine group. Based on these results, phase III development plans are underway.

Sosei announced negative results from a phase IIb trial of AD 452 for the treatment of rheumatoid arthritis. This randomized, double-blind, parallel group, placebo controlled trial enrolled 308 subjects in the US and Europe. Subjects were placed into one of three treatment groups and administered placebo or AD 452 at doses of 9 mg, 18 mg or 32 mg once daily for 12 weeks. The primary endpoint was ACR20 at week 12, a measurement developed by the American College of Rheumatology, defined as a 20% reduction in tender and swollen joints and a 20% reduction in 3 out of 5 standard rheumatology measurement tests. The primary endpoint was not met; statistical significance was not reached between the treatment groups and placebo. Of the subjects receiving Ad 452, 36% in the 9 mg dose group, 40% in the 18 mg group and 40% in the 36 mg group achieved ACR20 compared to 32% in the placebo group. Based on these results, Sosei has decided to discontinue development of Ad 452 for the treatment of rheumatoid arthritis and remove it from the priority pipeline.

November 13, 2006

CombinatoRx issued positive interim results from a phase II trial of CRx-102 for the treatment of rheumatoid arthritis. This multi-center, blinded, placebo-controlled, randomized trial enrolled 59 subjects who received CRx-102 plus a disease-modifying anti-rheumatic drug (DMARD) or placebo plus DMARD for six weeks. Treatment was well tolerated with no serious adverse events reported. The primary endpoint, reduction in C-reactive protein (CRP) levels from baseline at day 42, was achieved with a 50% median reduction compared to 19% with placebo (p=0.024). Secondary endpoints were met as well with a mean change in the Disease Activity Score (DAS28) of -1.6 from baseline to day 42 compared to -0.7 with placebo (p=0.016) and an ACR 20 score, designed to measure disease improvement showing a 63% response at day 42 compared to 30% with placebo (p=0.025). Based on these results CombinatoRx plans to continue with development of CRx-102.

November 6, 2006

NicOx announced positive results from a phase III trial of naproxcinod for the treatment of osteoarthritis of the knee. This 13-week, double-blind, placebo and naproxen-controlled trial randomized subjects into one of four treatment groups: naproxcinod 375 mg bid, naproxcinod 750 mg bid, naproxen 500 mg bid or placebo bid. Treatment showed good safety and tolerability profiles with the number of serious adverse events was low and similar across all treatment groups. Results were positive for all the primary endpoints, statistical significance in the mean change from baseline at week-13 in the WOMAC pain subscale, the WOMAC function subscale and patients' overall rating of disease status scores (p<0.001). Additional phase III trials are planned for 2007.

Regeneron issued positive results from a phase III trial of IL-1 Trap for the treatment of CIAS1-related autoinflammatory periodic syndromes (CAPS). This trial was conducted in two parts: Part A was a double-blind placebo-controlled trial in which subjects were randomized to receive a self-injected 160 mg dose of the IL-1 Trap or placebo once a week, for six weeks. Following a 9-week interval during which all subjects received a 160 mg dose of the IL-1 Trap, part B was initiated. This "randomized withdrawal" study re-randomized the same subjects to switch either to placebo or continue treatment with IL-1 Trap in a double-blind manner. The primary endpoint of both studies was the change in disease activity. The subjects in part A had an approximately 85% reduction in their mean symptom score compared to an approximately 13% reduction in those treated with placebo (p less than 0.0001). During the 9-week randomized withdrawal period, those who were switched to placebo had a five-fold increase in their mean symptom score, compared with those remaining on IL-1 Trap who had no significant change (p less than 0.001). Regeneron plans to file a BLA with the FDA for IL-1 Trap in the second quarter of 2007.

October 23, 2006

Array reported positive results from a phase I trial of ARRY-438162 for the treatment of inflammatory diseases. This randomized, placebo-controlled, double-blind, dose escalation trial enrolled 20 healthy volunteers who received ARRY-438162, once or twice a day, for 1 to 14 days. The single ascending dose portion of the study revealed that ARRY-438162 inhibited IL-1 (beta) by 50% to greater than 95% in samples where the drug concentration in plasma exceeded 50 ng/mL. The ongoing multiple ascending dose portion of the study has demonstrated linear increases in exposure with increasing dose. No serious adverse events through 14 days of continuous dosing occurred. Based on these results Array planned to move development of ARRY-438162 forward in late 2006 for the treatment of rheumatoid arthritis.

July 3, 2006

ZymoGenetics and Serono issued final results of a phase Ib trial of TACI-Ig for the treatment of rheumatoid arthritis (RA), at the 7th Annual European Congress of Rheumatology. This randomized, double-blind, placebo-controlled study enrolled 73 patients with moderate to severe disease, who received single or multiple doses of the drug or placebo for 3 months. Across all dose ranges and schedules, the drug appeared to be well tolerated, with no serious adverse events reported and mild injection site reactions observed most frequently. The drug demonstrated clear evidence of biological activity, including schedule- and dose-dependent decreases in the levels of immunoglobulin (Ig) and serum rheumatoid factors (IgM: -54%; IgA; -37%; and IgG: -21%). Preliminary efficacy was noted, including reductions in scores on the ACR and DAS 28 diagnostic measures. Based on these results, the company announced plans to initiate phase II trials of the drug in the second half of 2006.

June 26, 2006

Genmab and Amgen have issued efficacy data from a phase II trial of AMG 714, for the treatment of rheumatoid arthritis (RA) at the European League Against Rheumatism conference in Amsterdam. Results from the study yielded evidence of efficacy for the highest trial dose, with 59% of subjects (n=29/55) achieving ACR50 (a 50% improvement in symptom severity), and 25% (n=14/55) achieving ACR 70 at week 14, compared to 36% ACR50 (n=21/58) and 21% ACR70 (n=12/58) responses for placebo. This placebo-controlled dose-escalation study enrolled a total of 180 subjects who had failed at least 1 previous DMARD regimen. Subjects received 1 of 4 doses of the drug (40, 80, 160, or 280 mg) or placebo every 2 weeks for 12 weeks.

Human Genome Sciences issued positive results of a phase II trial of Lymphostat-B (belimumab), for the treatment of systemic lupus erythematosus (SLE). Trial data yielded evidence of efficacy in the co-primary endpoint, reducing SLE disease activity at week 52 on both the SELENA SLEDAI (p=0.04) and the Physician's Global Assessment (p<0.01) diagnostic scales and reducing risk of SLE flares from weeks 24-52 (p=0.04), Numerous secondary measures also showed improvement, including reductions in anti-dsDNA autoantibodies among baseline anti-dsDNA positive patients (p<0.01 at weeks 4-12: p<0.03 at weeks 16-24, and p<0.01 at weeks 32-52), levels of IgG, IgE, IgM and IgA immunoglobulins (p<0.02 at weeks 8-52), and B-cell subsets (CD19+ B-cells: p<0.01; CD20+/CD69+ activated B-cells: p<0.01; and CD20+/CD27- naive B-cells: p<0.01; at weeks 8-52; and CD20+/CD138+ plasmacytoid cells: p<0.01; at Weeks 16-52), and improvements in quality of life on the SF-36 diagnostic measure (p<0.05 at week 12, p=0.04 at week 52). This randomized, double-blind, placebo-controlled, dose-ranging superiority study enrolled 449 SLE patients, who received one of three intravenous doses (1, 4 or 10 mg/kg) of the drug or placebo on days 0, 14 and 28, then every 28 days through 52 weeks, in addition to current standard-of-care. Based on these results, the company announced plans to proceed with phase III trials of the drug.

March 27, 2006

Genmab has announced additional results of their recently completed phase I/II trial of HuMax-CD20 for the treatment of rheumatoid arthritis, including expanded American College of Rheumatology (ACR) diagnostic scale results. Trial data indicated that 38% (n=10/26) of subjects who received two doses of the drug at any dose level achieved an ACR50 response (a 50% or greater improvement in ACR score), and 15% (n=4/26) achieved an ACR70 response. Results were also provided by dose level: for the 300 mg dose, 25% (n=2/8) achieved ACR50 and 13% (n=1/8) achieved ACR70; for the 700 mg dose, 44% (n=4/9) achieved ACR50 and 22% (n=2/9) achieved ACR70; and for the 1000 mg group, 44% (n=4/9) achieved ACR50 and 11% (n=1/9) achieved ACR70. The company also revised their previously released ACR20 response rate: 1 subject included previously did not complete treatment, lowering the ACR20 response rate to 73% (n=19/26) among patients receiving treatment. This double-blind, randomized, placebo-controlled multi-center study enrolled 39 patients, 33 of whom received two administrations of one of 3 doses of the drug (300 mg, n=8; 700 mg, n=9; or 1000 mg, n=9) or placebo (n=7).

March 13, 2006

Genmab announced positive results of the first portion of a phase I/II trial of HuMax-CD20 for the treatment of rheumatoid arthritis (RA). Trial data indicated that 77% (n=20/26) of patients receiving both administrations of the drug achieved 20% improvement on the American College of Rheumatology diagnostic scale (ACR 20), compared to 0% for placebo. Response rates by dose were 75% (n=6/8) for the low trial dose, and 78% (n=7/9) for both the mid and high dose groups. Serious treatment related adverse events were observed, but these were in part mitigated by pre-medication with corticosteroids. This double-blind, randomized, placebo-controlled multi-center study enrolled 39 patients, 33 of whom received two administrations of one of 3 doses of the drug (300 mg, n=8; 700 mg, n=9; or 1000 mg, n=9) or placebo (n=7). This trial has been expanded into its second stage, enrolling 200 additional patients.

Vertex Pharmaceuticals issued positive results of a phase II trial, dubbed VeRA, of their investigational p38 MAP kinase inhibitor VX-702, for the treatment of RA. The drug was shown to significantly increase ACR20 response rates at 12 weeks, with 40% of subjects receiving high dose VX-702 and 38% of subjects receiving the lower dose achieving the measure, compared to 30% for placebo (p=0.04). Further, 44% and 42% of subjects receiving the drug (respectively) achieved a EULAR diagnostic response, vs. 32% for placebo (p=0.01), and significant reductions were noted in tender joint counts (p=0.007), swollen joint counts (p=0.003), disease activity score (p=0.02) and morning stiffness (p=0.03). Treatment was generally well tolerated, with study discontinuation rates of 5% and 3%, vs. 2% for placebo. No significant changes were noted in laboratory measures, and the majority of adverse events were mild to moderate and included incidence of infection (10% vs. 5%), gastrointestinal disorders (8% vs. 6%) and skin disorders (9% vs. 0%). This randomized, double-blind study enrolled 315 patients across more than 40 sites in Central and Eastern Europe; subjects received one of two doses of the drug (5 mg or 10 mg) or placebo once daily for 12 weeks. Based on these result, the company announced plans to initiate a phase II trial of the drug in combination with methotrexate by mid-2006.

January 16, 2006

ZymoGenetics and Serono reported positive results of a phase Ib trial of TACI-Ig for the treatment of rheumatoid arthritis (RA). Preliminary results indicated a positive tolerability profile, with no serious adverse events noted at any dose level, and no anti-TACI-Ig antibodies observed. Biological activity was also noted, with dose-dependent reductions in IgM, IgA, IgG, and rheumatoid factor disease markers. Preliminary efficacy was also noted in measures of disease symptom severity. This randomized, double-blind, placebo-controlled study enrolled 73 RA patients, who received single or multiple doses of the drug or placebo for 3 months.

November 7, 2005

Androclus reported results of a phase II trial of AT-001, for the treatment of rheumatoid arthritis (RA). Trial data yielded a positive safety and tolerability profile. Efficacy data failed to meet their primary endpoint, significance compared to placebo in combined AUC of ACR20 response rates at days 112, 140 and 168 (p=0.099). Post- hoc analysis did demonstrate significance in AUC of ACR20 response rates at days 112, 140, 168 and 196 (p=0.039). Response rates showed the greatest relative improvement on day 196 in ACR20 (35-45%; p=0.004), ACR50 (20-30%; p= 0.04), and ACR70 (10%-15%; p=0.1) response rates. This double-blind placebo-controlled study enrolled 160 RA patients across 11 US sites, who received 25 mg AT-001 or placebo once daily for 6 months.

October 24, 2005

Chelsea Therapeutics reported positive results of a phase Ia trial of their investigational anti- inflammatory drug CH-1504. Primary safety data were considered positive, with no serious adverse events reported and no clinically significant alterations in laboratory values for any dose, including levels higher than those predicted to be therapeutically relevant. Pharmacokinetic data yielded an elimination half-life suitable for once-daily dosing. This randomized, double-blind, placebo-controlled study enrolled 30 healthy volunteers at Guy's Hospital in London, who received single ascending doses in sequential cohorts. Based on these results, the company announced the initiation of a 24-subject phase Ib multiple-dose study of the drug.

June 13, 2005

Bristol-Myers Squibb issued positive results of their phase III "AIM" trial of abatacept, for the treatment of RA, at the European League Against Rheumatism (EULAR) meeting. Data indicated that abatacept significantly inhibited the progression of joint structural damage vs. placebo, as measured by radiographic analysis of joint erosion score (p=0.029), joint space narrowing score (p=0.009), and total score (p=0.012). Secondary efficacy was noted in reducing the incidence of increases in all three structural damage measures: joint erosion (0.63 vs. 1.14; p=0.008), joint space narrowing (0.58 vs. 1.18; p<0.001) and total score (1.21 vs. 2.32; p<0.001). Rates of overall adverse events were similar between abatacept and placebo, and serious adverse events occurred in 15% of subjects treated with abatacept and 11.9% of subjects treated with placebo. This one-year, double-blind, placebo-controlled, multicenter trial enrolled 652 patients with active RA who had achieved inadequate response on MTX. Subjects were randomized 2:1 to receive a 30 minute infusion of either 10 mg/kg abatacept or placebo on days 1, 15, 29 and every 28 days thereafter.

Genentech, Biogen-Idec, and Roche have issued positive results of their phase IIb "DANCER" trial of Rituxan (rituximab), their disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Results from the study yielded strong evidence of efficacy, with two Rituxan doses producing significantly greater portion of patients achieving 20% symptom relief (54% & 55%, vs. 28%), 50% relief (33% & 34%, vs. 13%), and 70% relief (13% & 20%, vs. 5%) vs. placebo at 24 weeks (p<0.05 for all values), as measured on the American College of Rheumatology diagnostic scale. Safety and tolerability data yielded no unexpected results, with the most frequent adverse events related to drug infusion and mild to moderate in intensity; these events could be reduced in incidence and severity by intravenous administration of corticosteroids prior to treatment. This dose-ranging, placebo-controlled study enrolled 465 rheumatoid arthritis patients whose disease was insufficiently treated by standard therapy with methotrexate (MTX). Subjects received one of several regimens of Rituxan or placebo, in addition to continuing MTX treatment.

April 4, 2005

Rigel Pharmaceuticals has reported positive results of a phase I trial of their disease-modifying antirheumatic drug (DMARD) R406, under development for the treatment of rheumatoid arthritis. Trial data met their primary safety endpoint, with no serious adverse events reported and a generally positive tolerability profile at doses believed to be clinically relevant. Pharmacokinetic/pharmacodynamic results demonstrated good oral bioavailability and a strong correlation between drug plasma levels and inhibition of Syk kinase, the drug’s molecular target. This sequentially designed trial enrolled patients in 2 stages: the first was a placebo-controlled, escalating single-dose human safety/pharmacokinetic study which enrolled 35 volunteers. The second stage was a placebo-controlled, multiple-dose safety study with an additional 24 volunteers. Based on these results, Guilford announced plans to move R406 into phase I/II safety and efficacy trial in the second half of 2005.

November 8, 2004

Genentech, Biogen Idec and Roche issued positive preliminary result from a phase IIb trial of their investigational monoclonal antibody Rituxan (rituximab) for the treatment of rheumatoid arthritis (RA). Trial data collected thus far have indicated that the drug met its primary endpoint, with a significantly greater portion of subjects achieving ACR 20 response levels at 24 weeks, compared to subjects receiving placebo. The drug also met its safety endpoints, with no significant increase in new or unexpected adverse events compared with baseline established in previous trials. This multi-center, randomized, double-blind, placebo-controlled study enrolled a total of 465 RA patients across sites in North America, Europe and Australia into one of nine dosing cohorts, including one of two doses of Rituxan or placebo in addition to one of two doses of corticosteroids or placebo; all subjects also received standard therapy with methotrexate.

October 25, 2004

Bristol-Myers Squibb reported positive results of two phase III clinical trials of their investigational drug abatacept, a T-cell co-stimulation modulator for the treatment of rheumatoid arthritis (RA). One-year results from the first study indicated that abatacept in combination with methotrexate, an approved disease-modifying antirheumatic drug (DMARD), produced a significant decrease in symptom severity: subjects receiving the combination showed significant improvements in the percentage of subjects achieving 20%, 50% and 70% reductions in American College of Rheumatology (ACR) symptom severity scores (p<0.001 for all three) versus subjects receiving methotrexate-plus-placebo. The drug combination also demonstrated efficacy in its secondary endpoints: a greater percentage of subjects achieved symptom remission after one year versus methotrexate-plus-placebo (23.8% vs. 1.9%; p<0.001), and radiographic evaluation demonstrated significant reductions in joint erosion (p=0.029), joint space narrowing (p=0.009) and total severity score (p=0.012). The second trial investigated abatacept or placebo in combination with at least one approved DMARD in RA patients showing inadequate response to TNF inhibitors. Six month data from this trial indicated that abatacept was efficacious in relieving RA symptoms in this population, with significant improvements in symptom scores versus placebo (ACR 20: 50.4% vs. 19.5%, p<0.001; ACR 50: 20.3% vs. 3.8%, p<0.001; ACR 70: 10.2% vs. 1.5%, p<0.03). Significant efficacy in the remission endpoint was also observed (10% vs. 0.8%; p<0.001). Both trials were double-blind, placebo- and approved-drug-controlled studies; the methotrexate enrolled a total of 547 subjects, and the TNF-inhibitor-resistant trial enrolled 391. Abatacept or placebo was administered on days 1, 15 and 29, followed by dosing once every four weeks for the extent of the trials.

October 18, 2004

AtheroGenics announced negative results of a phase II trial of AGIX-4207, for the treatment of rheumatoid arthritis (RA). Trial data failed to meet the primary efficacy endpoint, a significant increase in the number of patients achieving the American College of Rheumatology’s ACR-20 response standard (reduction of swollen joint count by at least 20 percent), compared with placebo. The trial also failed to meet certain secondary efficacy endpoints, including significant numbers of subjects reaching ACR-50 and ACR-70 response ratings, but did produce a significant reduction in tender-joint count and morning stiffness measurements. The double-blind, placebo-controlled study enrolled 275 mild-to-severe RA patients across centers throughout Europe, who were randomized to receive one of three single-daily-dose regimens of AGIX-4207 or placebo for 12 weeks. The company announced that, based upon these results, they were discontinuing development of AGIX-4207 for the treatment of RA.

June 21, 2004

Neurogen reported negative phase IIa study results for NGD 2000-1, an oral C5a inhibitor, for the treatment of rheumatoid arthritis (RA). Results indicated that NGD 2000-1 did not meet the study’s primary efficacy endpoint. This randomized, dose ranging, double-blind, placebo controlled study treated subjects with NGD 2000- or placebo twice daily for 14 days. No trial group achieved significant change in serum levels of C-reactive protein (a biomarker for disease activity), the trial’s primary endpoint. Subjects receiving the highest dose of the drug (100 mg), did meet one secondary endpoint (improvement on the ACR 20 diagnostic scale), and non-significant trends towards improvement were seen in a number of other secondary endpoints in all treatment groups. The study enrolled a total of 49 subjects with mild-to-moderate RA across 8 investigational sites. Neurogen announced that following these results, it is “unlikely” they will continue to pursue NGD 2000-1.

June 1, 2004

Androclus Therapeutics reported results from a phase I/IIa trial investigating AT-001 (dnaJP1), an engineered oral peptide for the treatment of rheumatoid arthritis (RA). Results demonstrated an induced a change from proinflammatory to regulatory T cell function. In addition, peptide-induced T cell production of IL-4 and IL-10 increased significantly while peptide-induced T cell proliferation and production of IL-2, interferon-gamma and TNF-alpha decreased significantly. Subjects were administered AT-001 orally for six months. Results from the open-label study were reported in the Proceedings of the National Academy of Sciences (March 23, 2004).

Theratechnologies and ALZA Corporation reported positive preliminary results from a phase I trial investigating ThPTH, a transdermal formulation of parathyroid hormone (PTH) for the treatment of osteoporosis. Results showed the rapid delivery and biologic activity of PTH, good bioavailability and a good safety profile. Data revealed that the patch delivered PTH, as measured by ELISA, at blood levels in the same range as subcutaneous administration. There were no serious adverse events reported. The first-in-human, cross-over design study enrolled 20 subjects. Subjects received a Macroflux-PTH patch and a subcutaneous injection of commercially available PTH (Forteo). The study was designed to determine the pharmacokinetic and pharmacodynamic profile of the Macroflux-PTH patch.<

April 5, 2004

Celltech Group reported positive preliminary results from a phase III trial investigating CDP870 for the treatment of rheumatoid arthritis (RA). Results showed the study met its primary endpoint, determined by the number of subjects achieving a 20% reduction in the American College of Rheumatology score ACR20 at 24 weeks. A significant ACR20 response was seen at week 1 and was maintained for the duration of the study. The six-month study (Study 014) was designed to test the safety and efficacy of CDP870 in combination with methotrexate on signs and symptoms of disease over a six month period. They trial enrolled subjects who had active moderate to severe RA despite treatment with methotrexate and other disease modifying anti-rheumatic drugs. In addition, Celltech announced plans to develop CDP870 for new indications, such as psoriasis, psoriatic arthritis and ankylosing spondylitis.

February 2, 2004

Alexion Pharmaceuticals reported preliminary results from a phase IIb study of eculizumab for the treatment of rheumatoid arthritis (RA). Results demonstrated that the primary endpoint was achieved with statistical significance in the monthly dosing arm. Data also demonstrated that monthly therapy showed evidence of a long-term anti-inflammatory effect, with a significant reduction in a key pre-specified objective measure of disease activity, ESR (erythrocyte sedimentation rate). The most common serious adverse events were myocardial infarction, accidental injury and cerebral infarction. The double-blind, randomized, placebo-controlled enrolled 350 subjects with chronic RA undergoing treatment with methotrexate or leflunomide. The primary efficacy endpoint was an ACR20 (American College of Rheumatology 20) improvement score after a six months period.

January 12, 2004

Isis Pharmaceuticals reported positive results from a phase II trial investigating ISIS 104838, an antisense TNF-alpha inhibitor for the treatment of rheumatoid arthritis (RA). Results showed the drug produced a statistically significant disease response in patients with RA. Data showed that 41% of subjects given ISIS-104838 achieved a 20% decrease in disease activity compared with 23% of placebo-treated subjects. The randomized, placebo-controlled trial enrolled 157 subjects with RA. Subjects received subcutaneous injections of ISIS 104838 (200 mg) or placebo. No drug-related serious adverse events were reported and injection site reaction was the most frequent adverse event.

November 18, 2002

Abbott Laboratories reported positive results from a phase III trial of Humira (adalimumab, D2E7), a monoclonal antibody for the treatment of rheumatoid arthritis (RA). The trial was designed to evaluate radiographic outcomes, efficacy and safety over a 52-week period. The study enrolled 619 subjects with active RA who had inadequate response to methotrexate (MTX). All subjects received stable doses of MTX and either Humira or placebo. The mean change of reduction in modified Sharp X-ray scores, which assesses changes in bone, for subjects receiving Humira (40 mg) plus MTX was 0.1 compared to 2.7 for subjects receiving placebo plus MTX. In addition, 62% of subjects receiving Humira (40 mg) experienced no new bone erosions compared to 46% of those receiving placebo.

November 4, 2002

Aventis and Vertex Pharmaceuticals reported positive results from a phase IIa trial investigating their interleukin-1 beta converting enzyme (ICE) inhibitor pralnacasan (HMR3480, VX-740), for the treatment of rheumatoid arthritis (RA). Subjects receiving pralnacasan (1200 mg) in the intention-to-treat population exhibited ACR20 response rates of 44% compared to response rates of 32.7% in the placebo group. In addition, data showed a statistically significant reduction in the inflammartory biomarkers C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A. The trial, a 12-week, double blind, randomized, placebo-controlled study was designed to evaluate the safety, efficacy, tolerability and steroid-sparing effects of pralnacasan in subjects with RA.

Bristol-Myers Squibb reported positive results of a phase II trial investigating CTLA4Ig (BMS-188667), a costimulation blocker, for the treatment of rheumatoid arthritis (RA). The study investigated CTLA4Ig in combination with etanercept, a tumor necrosis factor inhibitor, compared to etanercept alone. The primary endpoint of the study was the proportion of subjects meeting the ACR 20 criteria, a way of measuring subject improvement using ACR guidelines. By achieving ACR 20, a subject has at least a 20 % improvement in multiple measures of disease activity. Out of 85 subjects, 48.6% who had received CTLA4Ig (2 mg/kg) plus etanercept achieved ACR 20 compared to 27.8% who received placebo plus etanercept. Additionally, data demonstrated that 10.6% of subjects who received CTLA4Ig plus etanercept achieved ACR 70 compared to 0% in the placebo plus etanercept group.

September 30, 2002

Phase II results suggest that Genlab's Humax-CD4 was not effective in combination with methotrexate for the treatment of active rheumatoid arthritis (RA). One of four active dose groups of HuMax-CD4 (280 mg, 160 mg, 80 mg and 20 mg) plus methotrexate or placebo were administered to 155 subjects at weekly intervals for four weeks. At week seven, there was no significant difference between subjects receiving placebo compared to subjects treated with HuMax-CD4 in combination with methotrexate. In the placebo group, 24% of subjects achieved an American College of Rheumatology criteria score of ACR20 compared to 11% to 29% of subjects in dose groups receiving that score.

September 9, 2002

Genmab A/S's HuMax-IL15, an investigational drug for rheumatoid arthritis, showed favorable results in a phase I/II randomized, placebo controlled, dose escalation study. 30 subjects with rheumatoid arthritis who had previously failed to respond to disease modifying arthritis drugs (DMARDS) received placebo or one of six doses of HuMax-IL15, ranging from 0.15 mg/kg to 8 mg/kg. Subjects' response to the drug was measured by the American College of Rheumatology (ACR) scale, with ACR20 as the benchmark for efficacy. Results showed that over the four-week treatment period, 61% of subjects receiving HuMax-IL15 achieved an ACR20, 39% achieved an ACR50 and 26% achieved an ACR70. HuMax-IL15 was safe and well-tolerated in the trial.

June 24, 2002

Phase III trial results indicate that Abbott Laboratories' D2E7 (adalimumab) can be safely administered in combination with other disease modifying anti-rheumatic drugs (DMARDs). The 636-subject STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis) trial was designed to assess safety as a primary endpoint with a protocol that reflects the practice of prescribing a combination of DMARDs. Subjects were receiving up to four DMARDs when they were randomized to receive either placebo or 40 mg of D2E7 subcutaneously every other week (in addition to their current treatment). Results showed that there were no statistically significant differences in rates of serious adverse events or infections between placebo and D2E7-treated subjects after 24 weeks of therapy. Additionally, significantly more D2E7-treated subjects overall experienced an improvement of symptoms with ACR 20, ACR 50 and ACR 70 responses, compared to subjects receiving placebo.

June 3, 2002

Serono S.A. reported that they are discontinuing the development of IFN-beta-1a for the treatment of based on phase II study results. The randomized, double-blind, placebo-controlled trial enrolled subjects with active rheumatoid arthritis who did not respond adequately to methotrexate. The trial was designed to compare methotrexate alone to treatment with a combination of IFN-beta-1a and methotrexate. Data from the trial indicated that IFN-beta-1a did not provide additional benefit over treatment with methotrexate alone.

April 29, 2002

Phase II trial results indicate that Aventis and Vertex's pralnacasan produces anti-inflammatory effects in subjects with rheumatoid arthritis (RA). The 12-week, double-blind European trial was designed to evaluated pralnacasan alone and in combination with other treatments in subjects with active RA. Subjects were randomized to receive placebo or one of two doses of pralnacasan in addition to their current RA treatments (if any were being received). According to ACR20 response rates obtained after 12 weeks, pralnacasan-treated subjects exhibited a strong trend towards dose-dependent improvement in RA signs and symptoms. Subjects receiving the higher pralnacasan dose in the intention-to-treat population exhibited ACR20 response rates greater than 40%. Additionally, significant decreases in C-reactive protein, erythrocyte sedimentation rate and serum amyloid A were observed with the higher dose.

April 22, 2002

Positive results were reported from a phase I trial of intravenous (IV) AGIX-4207, a compound being developed for the signs and symptoms of rheumatoid arthritis (RA). Data from the trial, which enrolled healthy volunteers, demonstrated that single infusions of AGIX-4207 IV were well tolerated at all doses studied, including those that reached target blood levels. No dose-related increase in adverse events was observed. AGIX-4207 IV is being developed by AtheroGenics.

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.

Phase I trial results indicate that AGIX-4207, an oral treatment for rheumatoid arthritis, is safe and well tolerated in healthy subjects. In an ascending single-dose portion of the trial, 48 subjects received doses ranging from 1mg to 150mg. In a multiple-dose segment, 24 subjects received either 75mg or 150mg for seven consecutive days. AGIX-4207 was well tolerated over the single and multiple dose ranges, and adverse events were generally mild. Furthermore, subjects in the multiple-dose segment of the trial reached and maintained blood levels in the target range for the drug. AGIX-4207 is being developed by AtheroGenics.

January 24, 2002

Preliminary phase Ib trial results indicate that Regeneron Pharmaceuticals' Interleukin-1 Trap (IL1 Trap) produced dose-dependent improvements in tender and swollen joints, C-Reactive Protein (CRP) levels, and the composite ACR measure of disease activity. In the double-blind and placebo-controlled trial, the IL1 Trap was evaluated in four groups of 15-20 subjects with active rheumatoid arthritis. Each group received six weekly doses of IL1 Trap at one of four dose levels (0, 200, 400 or 800 micrograms/kilogram). Over 50% of subjects receiving the highest dose responded at the ACR-20 level, compared to approximately 30% of placebo-treated subjects.