Update for August 10, 2021

Regulatory Update
 
The FDA approved avalglucosidase alfa (Nexviazyme, Genzyme), on 8/6/2021, to treat patients 1 year of age and older with late-onset Pompe disease.
 
The FDA rejected the BLA for Spectrum Pharmaceuticals’ eflapegrastim due to deficiencies associated with the manufacturing of the drug.
 
The FDA placed a hold on Bluebird Bio’s elivaldogene autotemcel cerebral adrenoleukodystrophy (CALD) studies in August 2021, when a clinical trial patient developed myelodysplastic syndrome.
 
Marinus submitted an NDA for ganaxolone to treat seizures associated with CDKL5 deficiency disorder.
 
Announced Research Updates
 
BeyondSpring announced that in the 559 patient, Phase III DUBLIN-3 trial, treatment with plinabulin plus docetaxel improved overall survival compared to docetaxel alone in patients with non-small cell lung cancer (NSCLC) with EGFR wild type.
 
Dicerna announced that in the six-month, 35 patient, Phase II, PHYOX2 trial, treatment with nedosiran reduced urinary oxalate excretion 57.5% more than placebo in patients with primary hyperoxaluria (PH) type 1 and 2. Reduction in urinary oxalate excretion in 29 PH1 patients (23 nedosiran and 12 placebo) was significant, but not in six PH2 patients (5 nedosiran and 1 placebo).
 
Published Research Updates
 
ICER provided a final evidence report for aducanumab in early August 2021. In the report ICER found the evidence to be insufficient to support a slowing of cognitive decline in patients with mild disease. The report also stated that efficacy was not shown in patients with moderate to severe disease and no previous amyloid reducing drug trials have shown a benefit in moderate to severe disease. Most of the positive benefit identified in ENGAGE and EMERGE were from post-hoc analyses, so there is a reduction in the applicability of the findings, due to loss of randomization. ICER also noted that ARIA was seen in over a third of patients and questions whether it can be adequately monitored in practice. ICER estimates the cost-effective range of $2,950 to $8,360. ICER warns that care should be taken in the promotion of aducanumab to ensure that patients and families understand that aducanumab may slow the decline in cognition, but it will not improve cognition or quality of life.
 
In a 52-week, 119 patient extension of a 52-week, 121 patient, Phase III trial, patients treated for two-years with vosoritide achieved an increase in annualized growth velocity of 1.13 cm/year in the first year and by 1.26 cm/year after 2 years. Patients that were switched from placebo for the first year to vosoritide in the second year had a decrease in annualized growth velocity of 0.35 cm/year in the first year (on placebo), but increased growth velocity by 1.27 cm/year after 2 years (on vosoritide).
 
Interim data from a 289 patient, Phase III, trial, suggested that patients treated with toripalimab plus gemcitabine and cisplatin followed by toripalimab maintenance therapy achieved progression-free survival of 11.7 months compared to 8 months with gemcitabine and cisplatin alone followed by placebo maintenance treatment in Chinese patients with recurrent or metastatic nasopharyngeal carcinoma.
 
In the 476 patient, open label Phase III, VOYAGER trial, progression-free survival was no different with avapritinib compared to regorafenib in patients with gastrointestinal stromal tumors and a PDGFRA D842V-mutations.
 
In the 24-week, 257 patient, Phase , GENETIC-AF trial, treatment with bucindolol resulted in cumulative atrial fibrillation burden of 24.4% compared to 36.7% with metoprolol in patients with heart failure and the ADRB1 Arg389Arg genotype. 
 
In the 428 patients, 12-week, Phase III, CREDO 1 trial, ACR20 was achieved by 63.6% of patients treated with olokizumab every two weeks and 70.4% of patients that received olokizumab every four weeks compared to 25.9% with placebo in patients with rheumatoid arthritis inadequately treated with methotrexate.
 
In the 4-week, 57 patient, Phase II, PaTH Forward trial, 50% of patients treated with TransCon PTH achieved the composite endpoint (normal serum calcium, normal spot morning fractional excretion of calcium, not receiving vitamin D supplants and receiving less than 1000 mg/day of calcium) compared to 15% in the placebo group in patients with hypoparathyroidism. In a 24-month, 49 patient, open-label extension of the PaTH Forward trial, all patients received TransCon PTH with 71% achieving the composite endpoint.
 
In the ARIOS follow-up study of women being treated for spontaneous preterm labor, 49 infants whose mother had received retosiban were compared to 49 infants whose mother had received placebo or atosiban from two Phase III trials that were terminated early due to poor enrollment. Infants from the retosiban group had fewer serious adverse events (12.2% vs 6.1%). Neurodevelopmental delay was also less frequent at 18 months (0 vs 31.8%) and 24 months (8% vs 14.3%).
 
In a 608 patient, Phase III trial, entinostat plus exemestane did not improve overall survival or progression-free survival in patients with advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer that had progressed on a non-steroidal aromatase inhibitor.