Hematological Disorders

August 24, 2015

Omeros has released results of a phase II trial of OMS721 for the treatment of thrombotic microangiopathies (TMAs). The trial is designed to enroll primarily hemolytic uremic syndrome (aHUS) patients but also patients with thrombotic thrombocytopenic purpura (TTP) and hematopoietic stem cell transplant (HSCT)-related TMA. There was no placebo arm. In each three-patient cohort, OMS721 is dosed for four weeks. In this trial, platelet counts in all three aHUS patients in the mid- and high-dose cohorts (two in the mid-dose and one in the high-dose cohort) were normal after the treatment period, with a statistically significant mean increase from baseline of about 68,000 platelets/mL (p=0.0055). In the mid-dose cohort, the two patients with plasma therapy-resistant aHUS demonstrated 47% increase in mean platelet count, resulting in both patients having counts in the normal range; 86% decrease in mean schistocyte count, with schistocytes disappearing in one patient; 71% increase in mean haptoglobin, with both patients reaching the normal range during treatment and one slipping slightly below normal at one week following the last dose; and 5% decrease in the mean levels of LDH, with levels in both patients remaining slightly elevated above normal range. The company is discussing a phase III trial design with the FDA.

March 16, 2015

Portola Pharmaceuticals issued results of a phase III study of andexanet alfa in healthy volunteers. The randomized, doubleblind, placebo-controlled study evaluated andexanet alfa in reversing XARELTO-induced anticoagulation in healthy volunteers ages 50 to 75. 41 healthy volunteers were given XARELTO 20mg once daily for four days to steady state. They were then randomized in a 2:1 ratio to receive at Cmax either andexanet alfa administered as an 800mg IV bolus (n=27) or placebo (n=14). Results showed, for the primary endpoint, andexanet alfa reduced the anti-Factor Xa activity of rivaroxaban from baseline to nadir by >90%, a highly significant difference (p<0.0001). Significantly more andexanet alfa subjects (26 of 27) than placebo subjects (zero) had a 90% or greater reduction in anti-Factor Xa activity from baseline to nadir (p<0.0001). The free (unbound) XARELTO concentration from baseline to nadir was reduced significantly by andexanet alfa compared with placebo (p<0.0001). ETP significantly increased from baseline to peak in andexanet alfa subjects compared with placebo subjects (p<0.0001). 26 of 27 andexanet alfa subjects returned to the normal range of thrombin generation within 10 minutes of the end of the bolus administration. In the study, andexanet alfa was well-tolerated. There were no serious or severe adverse events, no thrombotic events and no antibodies to Factor X or Xa were observed. The company plans to submit these data as part of a BLA to the FDA by the end of 2015.

January 6, 2014

Incyte reported results of INCB39110 in a 12-week, open-label, dose-escalation phase II clinical trial involving more than 85 patients with intermediate or high-risk myelofibrosis (MF), all age 18 and classified as intermediate-1 or higher by Dynamic International Prognostic Scoring System (DIPSS). Patients were required to have a platelet count of = 50 x 109/L, hemoglobin = 8g/dL (transfusions permitted to achieve these levels), and a palpable spleen or prior splenectomy. In the preliminary analysis of an ongoing phase II trial that involved three doses (100mg twice daily, 200mg twice daily and 600mg once daily), treatment with INCB39110 at doses of 200mg twice daily and 600mg once daily provided meaningful improvements in MF-related symptoms, including symptoms associated with splenomegaly. At week 12, 22.2%, 34.9% and 50% of patients in the 100mg twice daily, 20mg twice daily and 600mg once daily dose groups, respectively, achieved at least a 50% improvement from baseline in their total symptom score (the primary endpoint); median percentage improvements from baseline at this time point were 28.5%, 45.8% and 76.8%, respectively, across dose groups. Reductions in spleen volume were modest, with median percentage changes from baseline to week 12 of 5%, -14.1% and -9.9%, respectively, across dose groups.

November 25, 2013

Relypsa released results of a phase IIb trial of patiromer as a treatment for hyperkalemia. The open-label, randomized, dose-ranging trial enrolled 306 patients. In the eight-week Treatment Initiation Period, patients were eligible for enrollment if they were hyperkalemic, had chronic kidney disease and type 2 diabetes mellitus and were taking a renin angiotensin aldosterone system (RAAS) inhibitor medication prior to screening. Patients were assigned to Stratum 1 (baseline serum potassium 5.1mEq/L to 5.5mEq/L) or Stratum 2 (baseline serum potassium 5.6mEq/L to less than 6mEq/L), and were randomized to one of three different starting doses of patiromer depending on the stratum. All patients could continue receiving patiromer in the 44-week Long-term Maintenance Period for a total of one year of treatment. For patients in Stratum 1, the change from baseline in serum potassium was –0.47mEq/L (95% CI -0.55, -0.40; p. For patients in Stratum 2, the change from baseline in serum potassium was –0.92mEq/L (95% CI -1.07, -0.78; p. Throughout the Long-Term Maintenance Period (following the eight-week Treatment Initiation Period), the mean serum potassium in both Stratum 1 and Stratum 2 remained in the target serum potassium range (3.8mEq/L to 5mEq/L). At week 52, the proportion of patients with a serum potassium in the target range was 85.5% in Stratum 1 (95% CI 78.7%, 90.8%) and 89.8% in Stratum 2 (95% CI 77.8%, 96.6%).

March 25, 2013

Isis Pharmaceuticals released results from a phase I trial of ISIS-CRPRx for the reduction of C-reactive protein (CRP) levels. This randomized, placebo-controlled, dose-response study enrolled 30 healthy volunteers. Subjects received six administrations of 400mg or 600mg ISIS-CRPRx over the course of 22 days (days 1, 3, 5, 8, 15 and 22) or placebo. At day 26, all subjects were administered an endotoxin challenge. Key inflammatory markers were measured just prior to and after the challenge. In this study, ISIS-CRPRx blunted severe increases in CRP levels by 63% (p=0.0011) in the 600mg cohort and 36% (p=0.023) in the 400mg cohort compared to placebo subjects at the time of peak CRP response (24 hours post challenge). No changes in other inflammatory markers were observed. Subjects receiving placebo had a mean baseline level of CRP of 1mg/L and experienced robust, acute increases of CRP levels of greater than 30 times normal levels after the endotoxin challenge, which returned to baseline after 72 hours. ISIS-CRPRx was well tolerated, with no serious adverse events observed and no dose limiting toxicities. Isis Pharmaceuticals is currently evaluating ISIS-CRPRx in a phase II study in rheumatoid arthritis, a disease where CRP is chronically elevated.

January 28, 2013

Spectrum Pharmaceuticals reported results from a phase I trial of RenaZorb for the treatment of hyperphosphatemia. This double-blind, dose-ranging study enrolled 32 patients with hyperphosphatemia and stage five chronic kidney disease (CKD). Subjects were divided into four sequential dose cohorts and received RenaZorb 1500mg, 3000mg, 4500mg or 6000mg daily, split into three doses each, or placebo. Results showed RenaZorb was well-tolerated up to the maximum administered dose of 6000mg. RenaZorb-treated subjects also showed statistically significant reductions in daily urinary phosphorous excretions at all four dose levels compared to placebo. RenaZorb showed no serious adverse events, low systemic exposure and no discontinuations of therapy. Based on these data, Spectrum Pharmaceuticals is planning for phase II trials and also is seeking a licensing partner outside of the U.S., specifically in Japan and other Asian countries.

December 3, 2012

AesRx released results from a phase I trial of Aes-103 for the treatment of sickle cell disease. This first-in-human, double-blind, placebo-controlled study enrolled 20 healthy volunteers of African-American descent. Subjects received single doses of Aes-103 at 300mg, 1000mg, 2000mg and 4000mg, or placebo. The pharmacokinetics of Aes-103 showed five-fold to 10-fold higher drug concentrations in red blood cells, which is the site of action of Aes-103 on hemoglobin, compared to drug concentrations in plasma. Aes-103 was rapidly absorbed and the amount of Aes-103 in plasma and red blood cells was largely dose proportional. In a hypoxia challenge test, subjects inhaled low levels of oxygen (12%) while their blood oxygen levels (SpO2%) were monitored. Aes-103 in 1000-4000mg doses reduced the hypoxia-related drop in subjects’ SpO2% compared to placebo and the 300mg dose. The drug’s ability to provide protection in a hypoxia challenge of healthy volunteers indicated biological activity in humans in a manner consistent with Aes-103’s proposed mechanism of action in sickle cell disease. Aes-103 was well tolerated. All adverse events were mild and transient. Based on these results, AesRx initiated a phase II trial of similar design enrolling patients with sickle cell disease.

October 22, 2012

Cyclacel Pharmaceuticals released results from an ongoing phase II trial of sapacitabine for the treatment of myelodysplastic syndromes (MDS). This randomized, open-label, multi-center study enrolled 63 patients aged 60 years or older with MDS of intermediate-2 (n=52) or high-risk (n=11) classification by the International Prognostic Scoring System (IPSS). Subjects were divided into three arms and received one of the following doses once every four weeks: sapacitabine 200mg twice daily for seven days (Arm G), 300mg once daily for seven days (Arm H), or 100mg once daily for five days per week for 2 weeks (Arm I). Results showed the median overall survival to date for all 63 patients is 252 days, or approximately eight months. Individual survival rates were 291 days for Arm G, 274 days for Arm H and 227 days for Arm I. Median overall survival for 41 out of 63 patients with 10% or more blasts in their bone marrow is 274 days, or approximately nine months. The drug was well tolerated. Cyclacel reported 22% of patients are still alive and longer follow-up is needed to assess one-year survival and overall survival of each arm.

October 1, 2012

Biogen Idec and Swedish Orphan Biovitrum released results from a phase III trial of rFIXFc for the treatment of hemophilia B. This open-label, multi-center, multi-arm study, B-LONG, enrolled 123 male patients aged 12 years and older. Subjects were divided into four arms and received rFIXFc 50IU/kg weekly as prophylaxis, rFIXFc 100IU/kg every 10 days as an individualized interval prophylaxis, episodic treatment or perioperative management. Data showed that the overall median annualized bleeding rates (including spontaneous and traumatic bleeds) were 2.95 in the weekly prophylaxis arm; 1.38 in the individualized interval prophylaxis arm; and 17.69 in the episodic treatment arm. In the individualized interval prophylaxis arm, the median dosing interval during the last six months on study was 14 days. Overall, 90.4% of bleeding episodes were controlled by a single injection of rFIXFc. The drug was well tolerated. The most frequent adverse events were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension and headache. Based on these findings, Biogen Idec plans to submit a Biologics License Application to the FDA in the first half of 2013. Additional analyses of the B-LONG study are ongoing.

July 16, 2012

Inspiration Biopharmaceuticals reported interim results from a phase II/III trial of OBI-1 for the treatment of acquired hemophilia A. The open-label study enrolled seven patients experiencing serious bleeds. Subjects received 200U/kg of OBI-1 on first injection and were subsequently dosed based on target FVIII levels. All seven subjects experienced successful control of bleeds at 24 hours and subsequent resolution of their bleeds. Therapeutic FVIII activity levels were achieved and maintained with intermittent OBI-1 administration based on FVIII levels. Of the adverse events reported during the study thus far, five were serious, but these were not considered by investigators to be treatment-related. Inspiration Biopharmaceuticals plans to continue the phase II/III trial.

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