April 2, 2018

Ablynx announced that the Phase II dose-ranging study of vobarilizumab, the Company's anti-IL-6R Nanobody, did not meet the primary endpoint of dose response based on the modified BILAG-based combined lupus assessment (mBICLA) at Week 24. This multi-center, randomized, double-blind, placebo-controlled, dose-range finding Phase II study enrolled 312 patients with moderate to severe, active seropositive SLE across the U.S., Europe, South America and Asia. The study enrolled patients across five treatment arms (four dose regimens of vobarilizumab and placebo). Safety findings through Week 58 were favourable for vobarilizumab. Treatment-related serious adverse events were reported in 2.0 percent of all vobarilizumab-treated patients compared to 6.5 percent in the placebo group. The percentage of patients experiencing a serious infection was also lower in the vobarilizumab arms compared to the placebo arm (2.8 percent versus 6.5 percent).

August 22, 2016

Aurinia Pharmaceuticals issued results of a phase IIb trial of voclosporin for active lupus nephritis (LN). The AURA–LV study enrolled 265 patients at centers in over 20 countries worldwide. Patients were randomized to one of two dosage groups of voclosporin (23.7mg BID and 39.5mg BID) or placebo, with all patients also receiving mycophenolate mofetil and oral corticosteroids as background therapy. All patients had an initial IV dose of steroids (500-1000mg) and then were started on 20-25mg/daily, which was tapered down to a low dose of 5mg daily by week eight and 2.5mg daily by week 16. The trial achieved its primary endpoint, demonstrating statistically significantly greater complete remission (CR) (as defined by confirmed urinary protein/creatinine ratio of =0.5mg/mg at 24 weeks and confirmed at 26 weeks) in patients treated with 23.7mg of voclosporin twice daily (p=0.045). Both treatment arms, 23.7mg and 35.9mg twice daily, also showed a statistically significant improvement in the rate of achieving partial remission at 24 weeks (p=0.007; p=0.024). No unexpected safety signals were observed and voclosporin was shown to be well-tolerated. Based on the results of the 24-week analysis, Aurinia plans to meet with the FDA in the fourth quarter of 2016 to discuss these data and the drug’s subsequent clinical development and path to registration in LN.

February 22, 2016

Aurinia Pharmaceuticals released results of an open label, single arm, exploratory study assessing the ability of biomarkers at eight weeks to predict clinical response rates at 24 and 48 weeks in subjects taking voclosporin 23.7mg twice daily in combination with standard-of-care, mycophenolate mofetil and corticosteroids, in patients with active lupus nephritis (LN). In the first seven patients that reached at least eight weeks of therapy in the AURION study, 100% (7/7) have achieved at least a 25% reduction in proteinuria compared to study entry. A 25% reduction in proteinuria has been shown to be predictive of a positive clinical response at 24weeks. All of the other pre-specified eight-week biomarkers of active LN have also improved and are trending towards normalization. These biomarkers have also been shown to be predictive of a positive clinical response at 24 weeks. In the first eight weeks of a 48 week regimen of multi-target therapy including voclosporin in AURION, an overall mean reduction of proteinuria of 72% compared to pre-treatment levels was observed, and 57% (4/7) of these patients achieved complete remission as defined by a urinary protein creatinine ratio of =0.5mg/mg. Overall renal function as measured by eGFR in these patients has remained stable. 

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 SoC 3.6%)].

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.

May 5, 2008

Genentech and Biogen reported negative results from a phase II/III trial of Rituxan for the treatment of systemic lupus erythematosus (SLE). This randomized, double-blind, placebo-controlled, multi-center study enrolled 257 subjects with moderate-to-severe SLE on a background immunosuppressant, in the US and Canada. The subjects received Rituxan plus prednisone or placebo plus prednisone in two infusions fifteen days apart. They were retreated six months later with the same regimen. Efficacy was evaluated every four weeks for fifty-two weeks. The primary endpoint, the proportion of subjects who achieved either a Major Clinical Response (MCR) or Partial Clinical Response (PCR) using the British Isles Lupus Assessment Group (BILAG) index compared to placebo at fifty-two weeks, was not reached. The study also did not meet any of the secondary endpoints, including time adjusted area-under-the-curve minus baseline of BILAG score over fifty-two weeks; proportion of subjects who achieve BILAG C or better in all domains at Week twenty-four; time to moderate or severe flare over 52 weeks; change in SLE Expanded Health Survey physical function score from baseline at Week fifty-two; and proportion of subjects who achieve a MCR with 10 mg prednisone per day from Weeks 24 to 52. A phase III trial of Rituxan evaluating lupus nephritis is currently underway and results are expected in Q1 of 2009.

August 20, 2007

Immunomedics reported positive results from a follow-up phase I/II trial of epratuzumab for the treatment of systemic lupus erythematosus (SLE). Phase I of the trial enrolled 12 subjects with SLE and analyzed the effect of epratuzumab on circulatory B-cell subsets. Results showed that epratuzumab preferentially targets naive and transitional B-cells. Phase II of the trial enrolled 11 subjects with SLE and 7 subjects without SLE. It was designed to analyze the effect of epratuzumab on the inhibition of the activation of B-cells. Epratuzumab stopped the over-activation of B-cells from SLE subjects but not normal B-cells, when activated by certain immune stimulating agents. Based on the results, Immunomedics plans to move forward with the development of epratuzumab.

ViroPharma and Wyeth announced negative results from a phase II trial of HCV-796 for the treatment of hepatitis C. This randomized, open-label trial placed subjects into one of three treatment groups: Group 1 was made up of treatment naive subjects who were to receive pegylated interferon and ribavirin (control therapy); Group 2 was made up of treatment naive subjects who were to receive pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours and Group 3 was made up of non-responding subjects who were to receive pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours. Primary outcomes included antiviral activity, the percentage of subjects with undetectable plasma HCV RNA levels at weeks 4, 12, 24, and 48 and the percentage of subjects with undetectable sustained virologic response (SVR). Interim safety data review showed elevated liver enzyme levels in 8% of HCV-796-treated subjects leading to the withdrawal of two subjects, compared with 1% in pegylated interferon plus ribavirin-treated subjects. Interim efficacy data showed that at weeks 4 and 12, 45% and 73% of treatment-naive HCV-796 plus pegylated interferon and ribavirin-treated subjects had undetectable HCV levels, compared with 7% and 39% of treatment-naive pegylated interferon and ribavirin-treated subjects, respectively. At total of 4% and 23% of HCV-796 plus pegylated interferon and ribavirin-treated subjects, previously unresponsive to treatment, had undetectable HCV levels at weeks 4 and 12, respectively. However, based on the negative safety data, ViroPharma and Wyeth discontinued the dosing of subjects enrolled in the trial.

July 2, 2007

Aspreva and Roche issued negative results from a phase III trial of CellCept for the treatment of lupus nephritis. This two-phase induction to maintenance study enrolled 370 subjects. It was designed as a randomized open label comparison of CellCept to intravenous cyclophosphamide (IVC) for the first six months (induction phase), followed by a double-blind comparison of CellCept to azathioprine for up to three years (maintenance phase). Treatment response in the induction phase was defined as a decrease in proteinuria and the stabilization or improvement of serum creatinine. Although response rates were similar between the two groups, the trial did not meet the primary endpoint of demonstrating that CellCept is superior to IVC in inducing treatment response. The response rate was 56.2% in the CellCept arm and 53% in the IVC arm. Treatment was well tolerated, with adverse events similar between the two arms. The maintenance phase of the trial is ongoing. Roche and Aspreva plan to further evaluate the data to determine the potential for a regulatory submission.

Gilead released positive results from a phase III trial of Viread for the treatment of "e" antigen (HBeAg)-positive chronic hepatitis B. This multi-center double-blind study, dubbed 103, enrolled 266 subjects who were randomized in a 2:1 ratio to receive either Viread (300 mg once daily) or Hepsera (10 mg once daily). The trial was designed to establish the non-inferiority of Viread to Hespera. The primary endpoint was the proportion of subjects with a complete response at week 48, defined by serum hepatitis B (HBV) DNA levels below 400 copies/mL and histologic improvement. This endpoint was achieved; 66.5% of subjects in the Viread arm had a complete response compared to 12.2% in the Hepsera arm (p less than 0.001), thus confirming non-inferiority. Adverse events were comparable between the two treatment arms. Based on the results, Gilead plans to file a NDA with the FDA and a MAA with the EMEA in the fourth quarter of 2007.