Weekly Update for the Week Ending November 9, 2019

Regulatory Update
 
The FDA approved luspatercept (Reblozyl, Celgene, Acceleron) on 11/8/2019 for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions.

The FDA is due to make a decision on Shionogi’s cefiderocol this week with a PDUFA date on 11/14/2019.
 
In 2013 the FDA rejected Aveo’s tivozanib 507 patient, Phase III, TIVO-1 trial as a pivotal renal cancer efficacy trial, due to inconsistencies in the overall survival and progression free survival results. In November 2019 the FDA expressed concern over the interim results presented from the TIVO-3 trial and felt it did not demonstrate improved overall survival and that final analysis may provide worse results. Aveo is planning to narrow its NDA for tivozanib to relapsed/refractory renal cell cancer, but the FDA will require approval of the new statistical analysis and a presentation of results to an advisory committee. Aveo could lose approval in Europe depending on the final results from the TIVO-3 trial.
 
The FDA accepted the NDA for Cassiopea’s clascoterone cream 1% for the treatment of acne and set a PDUFA date of Aug. 27, 2020.
 
Announced Research Updates
 
Halozyme announced that in a 500-patient, Phase III trial, treatment with PEGPH20 in combination with gemcitabine and nab-paclitaxel did not improve overall survival compared to gemcitabine and nab-paclitaxel alone (11.2 months vs 11.5 months) in patients with Stage IV previously untreated pancreatic ductal adenocarcinoma. Halozyme announced the discontinuation of the development of PEGPH20 after the failed Phase III trial. Halozyme is restructuring the company to focus on their ENHANZE drug delivery technology.
 
Scynexis announced that in the 376 patient, Phase III, VANISH-303 trial, treatment with ibrexafungerp resulted in clinical cure at day 10 in 50.5% of patients compared to placebo in female patients with vulvovaginal candidiasis.
 
Green Valley announced that in a 9-month, 818 patient, Phase III trial, patients treated with oligomannate had a decrease in their ADAS-Cog12 Score of 2.54 points less than placebo (2.7 vs 0.16) in Chinese patients with mild to moderate Alzhemer's disease. China granted conditional approval, with monitoring for safety for oligomannate to treat mild to moderate Alzheimer's disease and improve cognitive function. An editorial comment on the Chinese Phase III trial questioned if the improvement seen was accurate since few details on the trial are given and modulating neuroinflammation has not been shown to improve cognition in Alzheimer’s patients in earlier trials. 
 
AB Science SA announced that in a 36-week, 355 patient, Phase III trial, treatment with masitinib reduced the severe asthma exacerbation rate compared to placebo in patients with severe asthma uncontrolled by oral corticosteroids.
 
ObsEva announced that in the 10-week, 778 patient, Phase III IMPLANT4 trial, treatment with nolasiban did not improve the pregnancy rate compared to placebo (40.5% vs 39.1%) in women undergoing in vitro fertilization. ObsEva has discontinued development of nolasiban for in vitro fertilization.
 
MorphoSys announced that in a 48-week, 75 patient, Phase II trial, 96% of bimagrumab treated patients had lost at least 5% of their total body fat, and 77% had lost at least 15% of their total body fat in patients with obesity and type 2 diabetes.
 
Exelixis announced that in the 52-week, 455 patient, Phase III, ESAX-DN trial, treatment with esaxerenone reduced the urinary albumin-to-creatinine ratio 58.3% compared to an 8.3% decrease with placebo in patients with type 2 diabetes with microalbuminuria who were receiving an ACEI or ARB. 
 
Published Research Updates
 
In the 36.5-month, 16,071 patient, Phase III, LOFT trial, 3.7% of patients treated with odanacatib developed a vertebral fracture compared to 7.8% that received placebo in postmenopausal women with osteoporosis. An extension trial that included 8,257 patients from the LOFT trial, 4.9% of patients treated with odanacatib developed a vertebral fracture compared to 9.6% that received placebo after a total of 47.6 months. After 47.6 months the composite of cardiovascular death, myocardial infarction, or stroke occurred was 5% with odanacatib compared to 4.3% with placebo and stroke occurred in 2.3% of odanacatib patients compared to 1.7% with placebo in 8,257 postmenopausal women with osteoporosis enrolled in the LOFT and LOFT extension studies. Merck discontinued development of odanacatib due to the increased risk of cardiovascular events, specifically stroke.
 
In the 12-week, 378 patient Phase III, KALM-1 trial, 51.9% of patients treated with difelikefalin had a 3-point or > improvement in the weekly mean of the 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) compared to 30.9% with placebo in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus.