Systemic Lupus Erythematosus
November 30, 2015
GlaxoSmithKline has issued results of a
phase III pivotal study of Benlysta (belimumab)
in patients with active, autoantibody-positive
systemic lupus erythematosus (SLE).
BLISS-SC was a multicenter, randomized,
double-blind, placebo-controlled, 52-week
study. Of the 836 patients enrolled into the
study, 556 were randomized to receive belimumab
plus standard-of-care (SoC) and 280
were randomized to placebo plus SoC. Ninety-four
percent of the overall population in the
study were female. For the two pre-specified
secondary efficacy endpoints, the study
showed that the time to severe flare was
significantly delayed in patients receiving belimumab
administered subcutaneously plus
SoC (170 days, p=0.0003) compared to those
on placebo plus SoC (116.5 days). In addition,
in patients receiving more than 7.5mg/day of
prednisone (n=503),18.2% of patients receiving
belimumab administered subcutaneously
plus SoC in the study were able to reduce their
steroid dose by 25% or more to 7.5mg/day
during weeks 40-52, compared with 11.9% of
those on placebo plus SoC, but that result did
not reach statistical significance (p=0.0732).
The overall safety profile of belimumab in
BLISS-SC was consistent with that observed in
the two previous BLISS studies (BLISS-52 and
BLISS-76). The overall incidence of treatment-related
adverse events (AEs) was 31.3% with
belimumab administered subcutaneously
plus SoC v. 26.1% with placebo plus SoC—the
most common of which were infections/infestations
(belimumab administered subcutaneously
plus SoC 18.7% v. placebo plus SoC
18.9%) and general disorders and administration
site conditions, primarily injection
site-related events (belimumab administered
subcutaneously plus SoC 6.3% v. placebo plus
September 8, 2015
XTL Biopharmaceuticals has issued phase
IIb results of hCDR1 (Edratide) for the treatment
of systemic lupus erythematosus (SLE).
Dose-ranging studies demonstrated that the
0.5mg dose administered weekly as a subcutaneous
injection was the most effective dose and
that the drug showed no safety signals in the
26 week study. The study showed that Edratide
was safe and well-tolerated and while the primary
endpoints based solely on SLEDAI-2K and
AMS were not met, the secondary predefined
endpoint was met for the 0.5mg Edratide arm
in the intention-to-treat (ITT) cohort (N=316)
(OR=2.09, p=0.03) with trends in the 1 and
2.5mg doses. There was a positive trend in the
Composite SLE Responder Index of the ITT
cohort and post hoc analysis showed that the
BILAG secondary endpoint also was met for the
0.5mg Edratide for a number of subgroup dose
levels, including low or no steroids, seropositivity
and patients with 2 grade BILAG improvement.
The company believes favorable safety
profile and encouraging clinically significant
effects noted in some of the endpoints support
the need for additional longer-term Edratide
studies that incorporate recent advances in the
understanding and treatment of SLE, including
steroid treatment algorithms, and using a
composite primary endpoint.
July 23, 2012
Anthera issued further results from a phase IIb trial of blisibimod for systemic lupus erythematosus. This international, randomized, double-blind, placebo-controlled trial, PEARL-SC, enrolled 540 subjects. Patients were randomized into three active treatment arms (100mg weekly, 200mg weekly or 200mg monthly) and one placebo treatment arm for a minimum of 24 weeks. The primary endpoint of the PEARL-SC study was clinical improvement at 24 weeks in the SLE responder index. New data from the predefined population of subjects with severe disease who were also taking corticosteroids showed the SRI-8 treatment benefit in the 200mg weekly blisibimod cohort was observed as early as week eight and achieved statistical significance by week 16 (35.4% blisibimod response versus 17.0% placebo response, p=0.04) through the 24-week endpoint (41.7% blisibimod response versus 10.4% placebo response, p<0.001). Positive results regarding time to first severe flare, total flares, proteinuria and the proportion of patients achieving a reduction of steroid dose below 7.5mg per day were also demonstrated. Subjects in this population who were treated with 200mg of blisibimod weekly demonstrated a mean time to first severe flare of 1.6-fold longer than those treated with placebo (348 days versus to 223 days). The reduction in proteinuria at week 24 was significantly greater among patients in the blisibimod group compared to placebo (35.0% versus 5.1%, p=0.045). Full data from PEARL-SC will be presented at a future medical conference.
August 1, 2011
Neovacs issued preliminary results from a phase I/II trial of IFNα-Kinoid for the treatment of Systemic Lupus Erythematosus. This double-blind, ascending dose, placebo controlled study enrolled 28 subjects with moderate levels of lupus across Europe. The subjects received 30, 60, 120 or 240 mcg of the Kinoid or placebo over three months. The primary endpoint was safety. Secondary objectives included the immune response to the Kinoid, and measures of disease, including disease activity indices and markers for IFNα activity. These results are for the highest dose group entailing eight subjects (six receiving 240 mcg and two receiving placebo). Data showed the IFNα-Kinoid is highly immunogenic; antibodies to IFNα were induced in 100% of subjects treated with the Kinoid. Production of anti-interferon was rapid and titers were high. In addition, a significant reduction in interferon signature was observed in subjects treated with the IFNα-Kinoid: the IFN-K generated a significant downregulation of overexpressed genes associated to interferon α and lupus. The dose of 240 mcg of IFNα-K was well tolerated.
June 21, 2010
UCB and Immunomedics released results from a phase IIb trial of epratuzumab for systemic lupus erythematosus (SLE). This 12-week, multicenter, randomized, double-blind, placebo-controlled study randomized subjects to one of six intravenous regimens: placebo, epratuzumab cumulative dose (cd) 200, 800, 2400, or 3600 mg in equal divided doses using two every other week infusions or epratuzumab cd 2400 mg delivered as four equal infusions one week apart. The primary endpoint was responder rate on a combined index of clinical disease activity at week 12, including several indices of SLE disease activity, primarily emphasizing BILAG (British Isles Lupus Assessment Group) scoring. The combined responder index rates were numerically superior in all epratuzumab groups versus the placebo group, reaching statistical significance in the epratuzumab 600 mg weekly group (P≡0.0265) and the combined group of 74 subjects who received a cumulative dose of 2,400 mg (P≡0.0239) during the 12-week treatment cycle. In both these groups, responder rates were twice those of placebo.
November 9, 2009
Human Genome Sciences and GlaxoSmithKline reported positive results from a phase III trial of Benlysta (belimumab) for the treatment of systemic lupus erythematosus. This double-blind, placebo controlled trial, dubbed BLISS-76, enrolled 819 subjects across international sites. The subjects were randomized to belimumab (1 mg/kg or 10 mg/kg ) or placebo, all in addition to standard of care, dosed intravenously on days 0, 14 and 28, then every 28 days, extending for 76 weeks. The primary efficacy endpoint was patient response rate at week 52, as measured by the SLE Responder Index , which defines response as an improvement in SELENA SLEDAI score of 4 points or greater, with no clinically significant BILAG worsening and no clinically significant worsening in Physicians Global Assessment. Based on an intention-to-treat (ITT) analysis, belimumab 10 mg/kg met its primary efficacy endpoint of superiority versus placebo at Week 52. A statistically significant improvement was shown in the response rate for belimumab 10 mg/kg plus standard of care, vs. placebo plus standard of care, as measured by the SLE Responder Index at Week 52: 43.2% for 10 mg/kg belimumab, and 33.8% for placebo (p≡0.021). The 1 mg/kg dose plus standard of care did not achieve statistically significant improvement. Treatment was generally well tolerated. This trial will continue to Week 76.
February 9, 2009
ImmuPharma reported positive interim results from a phase IIb trial of Lupuzor for the treatment of systemic lupus erythematosus (SLE). This international, randomized, double-blind, placebo-controlled dose-ranging study had enrolled 147 subjects to date, 125 of whom were evaluable for efficacy. The subjects received two doses of subcutaneous Lupuzor plus standard of care versus placebo plus standard of care for 12 weeks. The primary endpoint was efficacy based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) response, defined as a decrease of at least 4 points in the SLEDAI score. Data demonstrated that a 200mcg dose of Lupuzor administered every four weeks was statistically significantly superior to placebo (p≡0.015). Lupuzor was generally well-tolerated with no significant drug related adverse events recorded. Based on the results, the recruitment of more patients was terminated and the subjects already randomized will continue the study to completion.
March 12, 2007
La Jolla announced positive interim data from a phase III trial of Riquent for the treatment of systemic lupus erythematosus. This double-blind, placebo-controlled, randomized trial enrolled 600 subjects who received Riquent (100 mg, 300 mg or 900 mg) or placebo for eight weeks. Treatment was well tolerated. Results revealed that the subjects treated with 300 mg or 900 mg per week doses of Riquent had higher reductions in antibodies to double-stranded DNA (dsDNA) than those treated with 100 mg per week or placebo. The results were significant for each Riquent dose group when compared to placebo (p < 0.0015 for 100 mg, p < 0.0001 for 300 mg and 900 mg). The median percent reductions in antibodies to dsDNA for the Riquent groups compared to placebo were 36% (100 mg), 48% (300 mg), and 66% (900 mg). La Jolla expects to report full data by the end of 2007.
July 31, 2006
ZymoGenetics announced preliminary results from two phase Ib trials of atacicept (TACI-Ig) for the treatment of systemic lupus erythematosus (SLE). The first study enrolled 49 subjects who received single or 4 weekly doses of atacicept or placebo via subcutaneous administration. The second study enrolled 24 subjects who received single or 2 doses 21 days apart of atacicept or placebo via intravenous administration. In both studies, atacicept appeared to be well tolerated across all dose levels and schedules. The most commonly reported adverse event was mild inflammation at the injection site. Preliminary efficacy results demonstrated biologic response corresponding to the drug's mechanism of action.
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.
October 10, 2005
Human Genome Sciences announced mixed results of a phase II trial of LymphoStat-B (belimumab), for the treatment of systemic lupus erythematosus (SLE). Trial data failed to meet either of the co-primary endpoints, producing neither statistically significant reductions in SLE symptom severity at 24 weeks on the SELENA SELDAI scale, nor increasing time to first disease flare through 52 weeks. However, the drug was found to produce a significant decline in SLE symptom severity at 52 weeks in the seropositive patient subgroup (~75% of subjects) compared to baseline on both the SELENA SLEDAI (p=0.021) and the Physician's Global Disease Assessment (p=0.016) scales; efficacy in this measure in the broader study population was non-significant, but trended positively. Also, the drug produced significant reductions vs. placebo in circulating B cell counts and anti-dsDNA autoantibodies in all treatment arms. This double-blind, placebo-controlled, dose-ranging study enrolled 449 SLE patients, who were to receive one of 3 doses of the drug (1 mg/kg, 4 mg/kg or 10 mg/kg) or placebo via intravenous infusion on days 0, 14 and 28, then at 28 day intervals through 52 weeks.
PharmaFrontiers issued positive interim results of a phase I/II trial of Tovaxin, for the treatment of multiple sclerosis (MS), at the ECTRIMS/ACTRIMS congress in Thessalonica, Greece. Trial data indicated that the drug reduced myelin-peptide reactive T cell counts dose dependently, with patients receiving the higher dose of the drug experiencing a 100% reduction at 5 weeks. These reductions strongly correlated with improvements on the Multiple Sclerosis Impact Scale (p<0.0086). Annual relapse rate was reduced by 92%, compared to baseline. No dose-limiting toxicities were observed. This dose-escalation study enrolled patients with relapsing-remitting or secondary-progressive MS, who received subcutaneous injections of either 6-9 million cells (low dose) or 30-45 million cells (high dose) at weeks 0, 4, 12 and 20.
July 25, 2005
Active Biotech reported positive results of a phase I trial of 57-57 for systemic lupus erythematosus (SLE). Trial data met primary safety endpoints, with no adverse events reported and a positive overall tolerability profile following both single and multiple ascending doses. Preliminary pharmacokinetic data yielded good oral bioavailability and an elimination half-life consistent with once-daily dosing. This open-label, single- and multiple- ascending dose study enrolled 30 healthy subjects at the Karolinska University Hospital in Stockholm, Sweden. Based on these results, the company announced plans to initiate a phase I study of the drug in SLE patients in the near future.
October 25, 2004
Immunomedics has announced initial results of a phase II study of epratuzumab, for the treatment of systemic lupus erythematosus (SLE). Preliminary results indicated that the drug was efficacious in treating SLE, with 64% of subjects reducing diagnostic-scale severity scores by 50% or more 24 hours post therapy. Furthermore, 86% of subjects returning for 6-month follow-up showed continued improvement. This open-label study enrolled a total of 14 subjects with SLE, who received 4 bi-weekly doses of the drug, for a total of 8 weeks. Epratuzumab is also under investigation for the treatment of B-cell malignancies.
October 11, 2004
Genelabs Technologies issued data from the preliminary analysis of their phase III trial of Prestara (prasterone), in women with systemic lupus erythemayosus (SLE). The reported data indicated that the trial did not meet its primary endpoint, an improvement in bone mineral density compared over placebo. This double-blind, placebo-controlled study enrolled women with SLE receiving glucocorticoids, and was designed to confirm the results of an early phase III trial, which found a bone-mineral-density increase following Prestara treatment in SLE women. This earlier trial was the basis for an Approvable letter from the FDA, who requested this newer trial be conducted before final approval could be issued. Genelabs announced that further analysis of the data was ongoing, and that they were planning to meet with the FDA to discuss the next steps in the development of Prestara.
April 28, 2003
Human Genome Sciences reported positive results from a phase I trial investigating LymphoStat-B, a human monoclonal antibody for the treatment of systemic lupus erythematosus (SLE). In the primary saftey endpoint, results showed that the treatment was well tolerated with no clinically significant adverse events or laboratory abnormalities. No drug-related serious adverse events were reported. In addition, data showed the half-life of LymphoStat-B to be consistent with that of other human monoclonal antibodies, and the drug significantly reduced the levels of circulating B (CD 20) cells. The double blind, placebo-controlled, dose-escalation trial enrolled 70 subjects and was designed to determine the safety and pharmacology of LymphoStat-B in subjects with SLE who were receiving standard therapies.
April 14, 2003
Genelabs Technologies and Johns Hopkins University School of Medicine reported positive results from a late phase trial investigating Prestara (prasterone), a synthetic androgenic hormone for the treatment of systemic lupus erythematosus (SLE or lupus). Results showed that Prestara improved or stabilized overall disease activity and symptoms without deterioration in women with active lupus. Subjects with a SLE Disease Activity Index (SLEDAI) score greater than two showed a 59% rate of response with Prestara compared with 45% on placebo. In addition, subject with a SLEDAI score greater than four showed a 60% rate of response with Prestara compared to 42% for placebo. SLEDAI is an index that measures disease activity by weighting the importance of each organ system involved.
La Jolla Pharmaceuticals reported positive results from phase II and phase III trials investigating Riquent, a B-cell antibody inhibitor for the treatment of lupus renal disease. Phase III trial results demonstrated that Riquent lowered levels of antibodies to double-stranded DNA; however, the trial did not reach statistical significance for its primary endpoint, time to renal flare. Data showed that 55% of Riquent-treated subjects (80/145) had sustained antibody reductions compared to 27% with placebo (41/153). The study enrolled 298 subjects who were treated for up to 22 months. Phase II trial results showed that 59% of Riquent-treated subjects (54/92) had sustained antibody reductions compared to 13% with placebo (13/97). The placebo-controlled study enrolled 189 subjects who were treated for up to 18 months.