Investigational Update for the Week Ending March 8

Three FDA Actions Last Week, Celgene’s Plans and Fourteen Research Updates

The FDA’s Vaccines and related Biological Products Advisory Committee voted to recommend approval for Sanofi’s Dengue vaccine for patients 9 to 17 years, but not in adult patients.

The FDA has granted fedratinib a priority review, with a PDUFA date of 9/3/2019. There are now twenty-five investigational drugs with PDUFA Dates between March 14, 2019 and December 25, 2019

The FDA removed the Breakthrough Therapy designation for oliceridine because current data did not support the designation. The FDA does feel the current safety data will support a refiled NDA after Trevena completes a Phase I safety study examining QT-interval prolongation.
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Celgene plans to submit an NDA for ozanimod in March 2019 and a BLA for luspatercept in April.

1. Vertex announced interim 4-week data from a Phase III trial, where VX-445 in combination with tezacaftor/ivacaftor demonstrated a mean improvement in ppFEV1 of 13.8% compared to a 0.2% loss with placebo in cystic fibrosis patients with one F508del mutation and one minimal function mutation. Vertex announced interim 4-week data from a 24-week Phase III trial, in which the addition of VX-445 to a combination of tezacaftor/ivacaftor demonstrated a mean improvement in ppFEV1 of 10.4% compared to a 0.4% improvement with placebo in cystic fibrosis patients with two F508del mutations already receiving tezacaftor and ivacaftor. Vertex plans to submit an NDA for either VX-445 or VX-659 in 3Q19 and a MAA in 4Q19.
2. Alnylam announced that in a Phase III trial, treatment with givosiran reduced the annualized rate of composite porphyria attacks compared to placebo in patients with acute hepatic porphyria. In the trial, 21% of givosiran patients experienced a serious adverse event compared to 9% with placebo. Alnylam is planning to begin a rolling NDA for givosiran in mid-2019, after full results from Phase III trials are available.
3. Menlo announced results from a Phase II trial, in which 33.3% of plaque psoriasis patients treated with serlopitant had at least a 4-point improvement in their Worst Itch Numeric Rating Scale score compared to 21.1% of patients that received placebo.
4. Shield announced that in a Phase IIIb trial, oral ferric maltol increased hemoglobin within 9% of the response rate seen with IV ferric carboxymaltose in patients with Iron Deficiency Anemia with inactive Inflammatory Bowel Disease in whom other oral iron therapies had failed.
5. Apellis has two ongoing Phase III trials evaluating APL-2 in the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Apellis halted enrollment in two trials in October 2018 due to the occurrence noninfectious inflammation. An investigation by Apellis determined the cause to be an impurity or contaminant from a change in the manufacturing process after Phase II trials. A correction has been made to the manufacturing process and Apellis dosed 10 patients in a Phase Ib geographic atrophy trial without incident. 
6. Ascendis announced that in a Phase III, open label trial, TransCon Growth Hormone was non-inferior to daily growth hormone (11.2 cm/year vs 10.3 cm/year) in children with pediatric growth hormone deficiency.
7. TG Therapeutics announced that in a phase II trial, treatment with ublituximab resulted in median B cell depletion of > 99%, a decrease in mean T2 lesion volume of 10%, and an annualized relapse rate of 0.07 with 93% of patients with relapsing multiple sclerosis being relapse free. TG Therapeutics has two Phase III trials comparing ublituximab to teriflunomide in the treatment of relapsing MS. Results are expected in mid-2020.
8. In a Phase III trial, the triglyceride levels of patients treated with Kowa Pharmaceuticals’ pemafibrate were reduced by 45% compared to placebo in patients with type 2 diabetes comorbid with hypertriglyceridemia. In a 28-week open label extension of the trial, pemafibrate maintained triglyceride reductions at 52 weeks (42.3 to 48.2%).
9. MyoKardia announced that interim data from 10 patients enrolled in a Phase II extension a trial, suggested that 8 patients treated with mavacamten had improved their NYHA Class and 7 were asymptomatic.
10. Allergan announced that rapastinel did not improve depression compared to placebo in three Phase III trials involving 1,510 patients with major depression disorder (MDD) who had a partial response to their current antidepressant therapy. Allergan is evaluating rapastinel monotherapy compared to placebo in the treatment of major depression disorder in a Phase III study and in a Phase II study of patients with MDD at imminent risk of suicide. 
11. Syndax announced that in a Phase Ib/II trial, entinostat in combination with atezolizumab did not improve progression free survival (PFS) in patients with triple negative breast cancer. Syndax announced that in a Phase Ib/II trial, entinostat in combination with avelumab did not improve PFS in patients with ovarian cancer. Syndax is evaluating entinostat in combination with exemestane in a Phase III trial of patients with advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer.
12. Eisai announced that in a Phase III trial, lemborexant reduced sleep latency compared to extended-release zolpidem or placebo. In a sub-analysis of 453 patients over the age of 65 from the trial sleep latency was reduced compared to extended-release zolpidem or placebo.
13. ViiV announced the results of two Phase III trials. In the 48-week, 616 patient, Phase III Atlas Trial, 92.5% of patients that received a monthly IM injection of cabotegravir and rilpivirine had an HIV-1 RNA < 50 copies/mL compared to 95.5% of patients that received a daily thee drug oral regimen of 2 NRTIs plus a third drug. In the 48-week, 566 patient, Phase III FLAIR trial, 93.6% of patients that received a monthly IM injection of cabotegravir and rilpivirine had an HIV-1 RNA < 50 copies/mL compared to 93.3% of patients that received daily abacavir/dolutegravir/lamivudine.
14. In an 8-week, 152 IBS-C patient Phase III trial, the mean change in serum phosphate from pooled data from 3 doses of Ardelyx’s tenapanor over the four weeks after treatment was completed was a 0.02 mg/dl increase in the pooled tenapanor group compared to a mean increase of 0.85 mg/dl in the placebo group in dialysis patients with hyperphosphatemia.​