Weekly Update for the Week Ending December 7, 2019

Regulatory Update
 
The FDA rejected Lexicon Pharmaceuticals/Sanofi’s sotagliflozin a second time as a treatment for type 1 diabetes on 12/2/2019. Previously, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee had a split decision (8-8) on sotagliflozin on whether to recommend approval of the drug as an add-on to insulin therapy in patients with type 1 diabetes in January 2019. Some members of the committee expressed concern regarding the increased risk for diabetic ketoacidosis with the drug. The FDA rejected sotagliflozin as a treatment for type 1 diabetes on 3/22/2019. The EMA approved sotagliflozin in April 2019 for the treatment of Type 1 Diabetes. Sanofi ceased participation in the development of sotagliflozin in July 2019 after the results from 3 Phase III type 2 diabetes trials were announced. 
 
The FDA rejected RVT-802 on 12/5/19 due to manufacturing issues.
 
Immunomedics resubmitted the BLA for sacituzumab govitecan for the treatment of resistant metastatic triple-negative breast cancer.
 
ViiV Healthcare submitted an NDA for fostemsavir in December 2019. Fostemsavir was bought from BMS in December 2015.
 
The FDA has placed a partial clinical hold on four of Clementia’s palovarotene trials [(two fibrodysplasia ossificans progressiva (FOP) studies and two osteochondroma studies)] due to reports of early growth plate closure in patients with FOP in patients under the age of 14.
 
Announced Research Updates

1. AB Science announced that in a 420 patient, Phase III trial, treatment with masitinib resulted in a decrease in severe asthma exacerbations compared to placebo in patients with severe asthma uncontrolled by oral corticosteroids.
2. Correvio announced that an analysis of the European SPECTRUM registry evaluated 1,289 episodes of recent-onset symptomatic AF in 1,120 ED patients with atrial fibrillation, where a single infusion of vernakalant converted 61% of cases to sinus rhythm and 70.2% of cases were converted that received a second dose. The analysis will be reviewed by the FDA's Cardiovascular and Renal Drugs Advisory Committee today, 12/10/2019.  Vernakalant has a PDUFA date this month of 12/24/2019. Vernakalant was rejected by the FDA in 2008, but approved in Europe and Canada in 2010. The SPECTRUM registry was initiated in 2010 at the request of the European Medicines Agency as a follow-up measure.
3. Aldeyra announced that in part 1 of the 12-week, 422 patient, Phase III, RENEW trial, dosing reproxalap four-times-daily for four weeks, followed by twice-daily dosing improved patient-reported ocular dryness score compared to placebo, but continuous dosing of the drugs four-times-daily did not improve symptoms compared to placebo in patients dry eye disease. Neither dosing regimen improved fluorescein nasal region staining score compared to placebo.
4. Sage Therapeutics announced that in the 15-day, 581 patient, Phase III, MOUNTAIN trial, treatment with zuranolone did not improve the HAMD-17 score compared to placebo (12.6 vs 11.2) in patients with major depressive disorder.
5. Aurinia announced that in a 52-week, 357 patient, Phase III, AURORA trial, 40.8% of patients treated with voclosporin achieved complete renal remission (UCPR of 0.5 mg/mg or <, eGFR 60 mL/min/1.73 m2 or < with no decrease of > 20% and no continuation of low dose corticosteroids or use of rescue medication) compared to 22.5% with placebo in lupus nephritis patients treated with mycophenolate mofetil and rapidly tapered low-dose oral corticosteroids. Aurinia plans to submit an NDA for voclosporin in the first half of 2020.
6. MyoKardia announced 48-week interim data from 12 patient enrolled in the Phase II extension of the PIONEER-HCM trial (PIONEER-OLE), suggested that 9/12 were asymptomatic and improvements in biomarkers, left ventricular ejection fraction and left ventricular outflow tract gradient were maintained at 48 weeks.
7. FerGene announced that in a 157 patient, Phase III, open-label trial, 53% of patients treated with nadofaragene firadenovec had a complete response at 3 months and 24% at 12 months in patients with BCG unresponsive non-muscle invasive bladder cancer.
8. UCB announced that in the 16-week, 478 patient, Phase III, BE SURE trial, more patients treated with bimekizumab achieved PASI 90 and an IGA score of clear or almost clear than adalimumab in patients with moderate-to-severe chronic plaque psoriasis. UCB plans submit for bimekizumab to treat moderate-to-severe plaque psoriasis in mid-2020.
9. Epizyme announced interim data from 99 patents enrolled in a Phase II study that suggested treatment with tazemetostat resulted in an overall response rate of 69% (31/45) in patients with EZH2 activating mutations follicular lymphoma and 35% (19/54) in patients with wild-type EZH2 follicular lymphoma.
10. Biohaven Pharmaceutical announced that interim data from 100 patients, who had completed 6-months of treatment in the Phase II/III, T2 Protect AD Study trial, suggested that treatment with troriluzole improved cognitive function or hippocampal volume in patients with mild-to-moderate Alzheimer's disease.
11. BMS announced that in the 269 patient, Phase I, TRANSCEND trial, treatment with lisocabtagene maraleucel resulted in a 73% overall response rate and a 53% complete response rate in patients with relapsed or refractory large B-cell lymphoma (LBCL). And in the 22 patient, Phase I/II, TRANSCEND CLL trial, treatment with lisocabtagene maraleucel resulted in a 81.5% overall response rate and a 45.5% complete response rate in patients with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
12. ObsEva announced that in the 535 patient, Phase III PRIMROSE 2 trial, heavy menstrual bleeding was reduced to 80/ml or less with the reduction being at least 50% from baseline in 93.9% of patients treated with linzagolix 200 mg and hormone add-back therapy and 56.7% with linzagolix 100 mg monotherapy compared to 29.4% with placebo in patients with uterine fibroids and heavy menstrual bleeding. The Phase III PRIMROSE 1 uterine fibroid trial is due to be completed in 2Q20. If the results for PRIMROSE 1 are positive, ObsEva plans to submit an MAA for linzagolix for the treatment of heavy menstrual bleeding associated with uterine fibroids by the end of 2020 and an NDA in early 2021.
13. J&J announced that in a 29 patient, Phase Ib CARTITUDE-1 trial, JNJ-4528 demonstrated an overall response rate of 100% and complete response of 69% in patients with relapsed multiple myeloma. 

Published Research Updates

1. A pooled analysis of six Phase II trials involving 103 patients found that midomafetamine (MDMA) added to psychotherapy resulted in 54.2% of patients not meeting CAPS-IV PTSD diagnostic criteria compared to 22.6% in the placebo group in patients with PTSD.
2. In a 12-week, 1,001 patient, Phase III trial, treatment with esaxerenone was noninferior to eplerenone for reductions in sitting and 24-hour BP in Japanese patients with essential hypertension. 
3. In the 1,672 patient, ACHIEVE I trial, the percentage of patients, who were pain free at two hours was 19.2% with ubrogepant 50 mg, 21.2% with 100 mg and 11.8% with placebo. The most bothersome symptoms at two hours were eliminated in 38.6% treated with ubrogepant 50 mg, 37.7% with 100 mg and 27.8% with placebo.
4. In a 32 patient cohort from a Phase II, advanced solid tumor, open-label trial, 18.8% of patients treated with tremelimumab had an objective response in patients with metastatic urothelial cancer.​
5. In the 350 patient, Phase III, TIVO-3 trial, patients treated with tivozanib had a median progression-free survival of 5.6 months compared to 3.9 months with sorafenib in patients with with highly refractory advanced or metastatic renal cell carcinoma that had failed at least two prior therapies, including a vascular EGFR TKI.