Investigation Drug Update for the Week Ending February 15

During the week ending, 2/15/2019, the FDA approved one drug, rejected another, had a recommendation for approval by an advisory committee and set PDFA dates on two drugs. There were also eight notable clinical updates that we added to our database along with the FDA actions. 
FDA Actions

1. The FDA approved triclabendazole (Egaten from Novartis) on 2/13/2019 for the treatment of fascioliasis.
   
2. The FDA rejected Motif Bio’s iclaprim due to concerns over liver toxicity and requested additional liver toxicity data. Iclaprim has Fast Track status and is designated a Qualified Infectious Disease Product by the FDA.
   
3. An FDA review of J&J’s esketamine nasal spray for the treatment of depression, questioned whether enough efficacy data was available for approval. There was one positive short-term trial, one trial that found no significant difference and one withdrawal trial. The FDA did not consider the withdrawal trial as an efficacy study. On 2/12/2019 the Psychopharmacologic Drugs Advisory Committee (PDAC) and Drug Safety and Risk Management (DSARM) Advisory Committee voted 14-2 for effectiveness and that benefit outweighs risks and 15-2 that the drug had an acceptable safety profile. Eketamine is designated a breakthrough therapy by the FDA.
   
4. The FDA accepted the NDA for Bioproject Pharma’s pitolisant on 2/12/2019, which suggests a PDUFA date of 8/12/2019. Pitolisant has both Fast Track and Breakthrough Therapy status.
   
5. The FDA accepted the NDA for Sarepta Therapeutics’ golodirsen on 2/14/2019 and set a PDUFA date of 8/19/2019.

Clinical Updates

1. In a-52 week, 189 patient, Phase III, open label trial, treatment with pemafibrate resulted in a 45.9% decrease in triglycerides and did not appear to be affected by eGFR in patients with hypertriglyceridemia and chronic kidney disease. Pemafibrate also did not appear to increase ADR in patients with hypertriglyceridemia and chronic kidney disease.
2. Gilead announced that in the 48-week, 877 patient, Phase III, STELLAR-4 trial, treatment with selonsertib did not improve liver fibrosis by 1 stage or more without disease worsening compared to placebo (12.5-14.4% vs 12.8%) in patients with compensated cirrhosis due to NASH. Gilead has an ongoing Phase III, STELLAR-3 trial evaluating selonsertib in patients with bridging fibrosis due to NASH. Results are expected in 2Q18. Selonsertib is also being evaluated in combination with the FXR agonist cilofexor and the ACC inhibitor firsocostat in the Phase II ATLAS study of patients with advanced fibrosis due to NASH. 
   
3. ReGenTree is evaluating RGN-259 in the 700 patient, Phase III, ARISE-3 trial in patients with dry eye syndrome. The ARISE-3 trial is expected to conclude in the first half of 2020.
   
4. In a 46-week, 90 patient, Phase II trial, patients treated with cediranib and olaparib had a 16.5-month progression-free survival (PFS) compared to 8.2 months in patients treated with olaparib monotherapy in patients with relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1/2 mutation (gBRCAm). Improved survival was seen with the combination in gBRCA wild-type/unknown patients.
   
5. In a 50 patient, Phase II, open label trial, 52% of patients treated with pracinostat and azacitidine achieved the combined primary endpoint of complete remission (42%), complete remission with incomplete count recovery (4%), and morphologic leukemia-free state (6%) in patients with newly diagnosed AML that were ineligible for standard induction chemotherapy. 
   
6. Immunomedics announced that in a 45 patient, Phase I/II, open label, basket study, treatment with sacituzumab govitecan resulted in an overall response rate of 31% and a median duration of response of 12.6 months in patients with advanced solid tumors who had received from 1-6 previous lines of treatment.
   
7. AZ announced that in the 41 patient, Phase II CALYPSO trial, savolitinib and durvalumab induced an overall response rate of 27% in patients with metastatic papillary renal cell carcinoma.
   
8. DBV Technologies plans to resubmit a BLA for the Viaskin peanut patch in the second half of 2019.