FDA Approves One, Delays Another, Grants New Orphan Drug

Regulatory Actions

The FDA approved netarsudil and latanoprost ophthalmic solution (Rocklatan, Aerie Pharmaceuticals) on 3/13/2019 to decrease elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
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 In March 2019, the FDA delayed the PDUFA date for Karyopharm Therapeutics’ selinexor by three months (from April 6, 2019 to July 6, 2019).

The FDA accepted the NDA for ubrogepant on 3/11/2019. Allergan expects a 4Q19 PDUFA date of 12/27/19
 
The FDA accepted the NDA for lemborexant on 3/11/2019. Allergan expects a 4Q19 PDUFA date of 12/27/19
 
The FDA granted Orphan Drug status to Armetheon’s tecarfarin for the prevention of systemic thromboembolism of cardiac origin in patients with End Stage Renal Disease (ESRD) and Atrial Fibrillation (AFib).

Celgene filed an MAA filed for ozanimod in March 2019.

New Published Research 

In a Phase III, open label, follow-up safety study, 49% completed the Alkermes samidorphan/buprenorphine study and had a mean MADRS score decrease from 22.9 at baseline to 9.8 with a remission rate of 52.5%. There were 11% of patients that discontinued due to an adverse event. The most common ADR were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of an increased risk for suicidal ideation or behavior or withdrawal. There was a 1.2% incidence of euphoria-related events. No meaningful changes in laboratory values, metabolic parameters or bodyweight were found.

In a 12-week, 2,230 patient, Phase III trial, Esperion Therapeutics’ bempedoic acid lowered LDL 18% compared to a 2% increase with placebo in patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both not adequately controlled on maximally tolerated statins. The frequency of ADR at 52 weeks was similar between bempedoic acid and placebo for all events (78.5% and 78.7%) or serious events (14.5% and 14.0%). Bempedoic acid patients experienced more gout (1.2% vs 0.3%). This was a non-significant increased incidence of heart failure hospitalizations and increased mortality, but the incidence was 0.5% or less.

New Announced Research 

TG Therapeutics announced interim data from 69 patients in the open label, Phase II, UNITY-NHL trial. The UNITY-NHL trial is evaluating umbralisib as a treatment for multiple kinds of Non-Hodgkin's lymphoma. A cohort of 69 patients with Marginal Zone Lymphoma had an overall response rate of 40-50%. TG Therapeutics expects to file an NDA for umbralisib in late 2019.

A 35 patient, Phase II resistant renal cell carcinoma trial was stopped early due to inadequate response with Amgen’s trebananib and an anti-VEGF agent.

Akebia announced interim data at 24 weeks from a 52-week, 304 Japanese patient, Phase III, open label trial, where vadadustat was non-inferior to darbepoetin alfa in mean Hb (11.66 g/dL vs 11.93 g/dL) in patients with non-dialysis dependent CKD. Akebia also announced interim data at 24 weeks from a 52-week, 323 Japanese patient, Phase III, trial, in which vadadustat was non-inferior to darbepoetin alfa in mean Hb (10.61 g/dL vs 10 g/.65dL) in patients with hemodialysis-dependent CKD. Akebia announced that in a 24-week, 42 Japanese patient, Phase III, open label trial, treatment with vadadustat resulted in a mean Hb of 11.35 g/dL in patients with peritoneal dialysis-dependent CKD.

Arena announced that in the 12-week, 156 patient, Phase II, OASIS trial, treatment with etrasimod improved the Mayo Clinic Score (a composite of rectal bleeding, stool frequency, and endoscopic findings) 1 point more than placebo in patients with moderate to severe ulcerative colitis. Etrasimod 2 mg, but not 1 mg achieved endoscopic improvement (16.3% vs. 43.2%), histological improvement (10.2% vs. 31.7%), and histological remission (6.1% vs. 19.5%) compared to placebo. Arena also announced that in a 34-week, 118 patient open label extension of the OASIS trial 84 patients received 2 mg of etrasimod during the extension study with 79% achieving a clinical response, 39% achieving clinical remission and 51% had endoscopic at 46 weeks. Among 22 patients who also received 2 mg of etrasimod during the OASIS trial, 82% experience clinical response, 50% were in clinical remission and 55% had endoscopic improvement. In the patients that achieved a clinical response or clinical remission in OASIS, 93% experienced sustained response and 75% experienced sustained remission at both 12 and 46 weeks.

Lilly announced that in a 12-week, 249 patient, Phase II trial, treatment with mirikizumab 200 mg resulted in greater remissions than placebo in patients with moderate-to-severe ulcerative colitis who had failed at least one conventional drug. Treatment with 50 mg or 600 mg was no different than placebo. Patients that achieved a clinical response at week 12 (93 patients) were randomly reassigned to mirikizumab 200 mg subcutaneously every 4 weeks or every 12 weeks. At week 52, 46.8% of the q4w patients and 37% of the q12w patients were in clinical remission, while 57.4% of q4w patients and 47.8% of the q12w patients had endoscopic scores of zero or one.

Bayer announced that in the 52-week, 330 patient, Phase III, CHICO trial, treatment with 60 days of nifurtimox resulted in a superior serological response compared with historical placebo control in pediatric patients with acute or chronic Chagas disease.