Investigational Update for the Week Ending March 29

Regulatory Updates

• In January 2019, the FDA delayed the PDUFA date for bremelanotide and set a new date of 6/23/2019. 
• The FDA granted recombinant human pentraxin 2 breakthrough therapy status.
• Celgene resubmitted an NDA for ozanimod in March 2019. 
• Santhera filed an MAA for idebenone in March 2019.
• SRP-4045 has been assigned the generic name of casimersen.
• Bluebird changed the brand name for beta beglogene darolentivec to Zynteglo. Previously it was called LentiGlobin. CHMP recommend approval of beta beglogene darolentivec in March 2019.

Newly Published Trial Results

1. In a 133 patient, Phase III trial, patients treated with anlotinib had a similar PFS compared to sunitinib (17.5 vs. 16.6 months) as initial treatment in patients with metastatic renal cell carcinoma. 
2. In a 14-week, 671 patient, Phase III trial, mirogabalin 15, 20, or 30 mg/day decreased the average daily pain score -0.41, -0.47, and -0.77 compared to placebo in patients with postherpetic neuralgia.
3. In a 24-week, 216 patient, Phase III, open label trial, daprodustat increased hemoglobin by 0.69 g/dL after 4 weeks and maintained the level at 24 weeks in hemodialysis patients with anemia switched from a stable dose of epoetin to daprodustat. In a 24-week, 252 patient, Phase III, open label trial, daprodustat maintained hemoglobin at 24 weeks in chronic kidney disease patients with anemia switched from a stable dose of epoetin to daprodustat.
4. In a 52-week, 166 patient, open label, extension trial, treatment with pemafibrate resulted in a 42.3 to 48.2% decrease in triglycerides in patients with hypertriglyceridemia and Type 2 diabetes.
5. In an 8-week, 222 patient, dose-ranging trial, viloxazine improved the ADHD Rating Scale (RS)-IV total score for 200, 300 and 400 mg compared to placebo in children aged 6 to 12 years of age with attention deficit hyperactivity disorder.
6. In a 122 patient, Phase II trial, 54% of patients treated with polatuzumab vedotin/rituximab (n=39) had an objective response and 21% had a complete response, compared to an objective response in 60% of patients and a complete response in 26% of patients treated with pinatuzumab vedotin/rituximab (n=42) in patients with diffuse large B-cell lymphoma. In the same trial 70% of patients treated with polatuzumab vedotin/rituximab (n=20) had an objective response and 45% had a complete response, compared to an objective response in 62% of patients and a complete response in 5% of patients treated with pinatuzumab vedotin/rituximab (n=21) in patients with follicular lymphoma.

New Trial Results Announced

1. Aldeyra announced that in the 318 patient, Phase III, ALLEVIATE trial, a greater percentage of patients treated with reproxalap 0.25% and 0.5% ophthalmic solutions reduced the ocular itch score within 10 to 60 minutes after allergen challenge compared to placebo in patients with seasonal allergic conjunctivitis.
2. Novartis treated 137 patients with open label osilodrostat for 24 weeks. Patients that had been on a stable dose since week 12 and had a UFC in normal range were randomized to osilodrostat or placebo for 8 weeks. In the 70 patients that were included in the Phase III trial, 86% of patients treated with osilodrostat had a UFC in the normal range compared to 29% of those switched to placebo in patients with Cushing's disease. Current trial data display no significant safety concerns; no independent safety data are yet available. In a 137 patient Phase III trial, the most common ADR with osilodrostat were nausea, headache, fatigue and adrenal insufficiency. Almost 11% discontinued treatment due to ADRs.  
3. Aimmune announced that in the 9-month, 175 patient, Phase III ARTEMIS trial, treatment with AR101 resulted in a median tolerated dose of peanut protein of 1000mg in pediatric patients with peanut allergy. 
4. Proteon announced that in the 12-month, 603 patient, Phase III, PATENCY 2 trial, treatment with vonapanitase did not reduce fistula use for hemodialysis or secondary patency compared to placebo in hemodialysis patients with a new radiocephalic fistula.
5. Sarepta announced interim results at 48-weeks from the 96-week, 43 patient, Phase III, ESSENCE trial, where casimersen increased mean dystrophin protein levels compared to placebo in patients with Duchenne Muscular Dystrophy amenable to skipping exons 45. Sarepta plans to submit an NDA in mid-2019.
6. Astellas and Seattle Genetics announced interim results from a 128 patient cohort enrolled in a Phase II, open label trial, where treatment with enfortumab vedotin resulted in a 44% objective response rate in patients with locally advanced or metastatic urothelial cancer who progressed after receiving platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.
7. Gilead and Galapagos announced interim 24-week data from the 52-week, 1,759 patient, Phase III, FINCH 1 trial, in which filgotinib was superior to placebo in achieving ACR20/50/70 with filgotinib 200 mg (76.6%, 47.2%, 26.3%), filgotinib 100 mg (69.8%, 36.3%, 18.5%) compared to adalimumab (70.8%, 35.1%, 14.2%) and placebo (49.9%, 19.8%, 6.7%) in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate (MTX). Gilead and Galapagos announced interim data from the 24-week, 1,252 patient, Phase III, FINCH 3 trial, where filgotinib/MTX was superior to MTX monotherapy in achieving ACR20/50/70 with filgotinib 200 mg/MTX (81%, 61.5%, 43.8%), filgotinib 100 mg/MTX (80.2%, 57%, 40.1%) compared to filgotinib 200 mg (78.1%, 58.1%, 40%) and methotrexate (71.4%, 45.7%, 26%) in patients with with moderate-to-severe rheumatoid arthritis naive to methotrexate.