Weekly Update for the Week Ending September 14, 2019

Regulatory Update
 
The FDA approved tenapanor (Ibsrela, Ardelyx) on 9/12/2019 for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults. The most common adverse event with tenapanor is diarrhea. The drug is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
 
The FDA designated Ridgeback Biotherapeutics’ mAb114 a Breakthrough Therapy for the treatment of Ebola.
 
The FDA accepted the BLA forHorizon Therapeutics’ teprotumumabfor the treatment of active thyroid eye disease in September 2019 and set a PDUFA date of 3/8/2020, with an Orphan Drug Priority Designation. 
 
The FDA has accepted Allergan/Actavis/Molecular Partners’NDA and the EMA accepted the MAA for abicipar pegol for the treatment of neovascular age-related macular degeneration (wet AMD) in September 2019 with approval anticipated in mid to late 2020.
 
The FDA's Allergenic Products Advisory Committee voted 7 –2in favoron efficacy and 8-1 in favor on safety for use of AR101 to reduce the incidence and severity of peanut allergy reaction in patients aged 4-7. It is likely AR101 will be approved with a REMS program that will require a prescription for epinephrine. Aimmune is considering pricing AR101 between $3,000 and $20,000 when the drug is approved. As a comparison, the current discounted price for grass and pollen allergy products is $5,000 a year.An FDA review of the drug found that despite both placebo and AR101 groups following a peanut avoidance diet, the AR101 group had an increased number of discontinuations, systemic allergic reactions and reports of eosinophilic esophagitis, but reduced the need for treatment after accidental exposure.
 
Announced Research Updates
 
Lilly announced interim data from the 105 patient, Phase I/II LIBRETTO-001, open-label trial, where treatment with selpercatinib resulted in a 68% overall response rate, a median duration of response of 20.3 months and progression free survival of 18.4 months in patients with RET fusion-positive non-small cell lung cancer, previously treated with platinum-based chemotherapy. Lilly plans to submit an NDA for Selpercatinib by the end of 2019 with potential approval in 2020.
 
Axon announced that in the 24-month, 196 patient, Phase II, ADAMANT trial, treatment with AADvac1 resulted in a 12.6% decrease in Neurofilament Light Chain (a biomarker of neurodegeneration and neuronal loss) compared to a 27.7% decrease with placebo in patients with mild Alzheimer's Disease.
 
Alnylam announced that in the six-month, 94 patient, Phase III, ENVISION trial, patients treated with givosiran had a mean annualized porphyria attack rate of 1.0 compared to 10.7 attacks with placebo in patients with acute hepatic porphyria. An open-label extension of the Envision trial enrolled 93 patients from the original trial where the reduction in the annualized porphyria attack rate with givosiran was sustained.
 
Biogen and Eisai ceased development of elenbecestat in September 2019 after the drug’s independent monitoring board expressed concerns about safety.
 
Biogen announced 18-month interim data from 888 patients enrolled in the 2-year, Phase III, open label, EVOLVE-MS-1 trial, where treatment with diroximel fumarate resulted in a 79.4% reduction in the annualized multiple sclerosis relapse rate in patients with relapsing-remitting multiple sclerosis, who previously received interferon or glatiramer acetate.
 
Johnson & Johnson announced that in the 108-week, 1,133 patient, Phase III, OPTIMUM trial, treatment with ponesimod reduced the annualized relapse rate by 30.5% compared teriflunomide (0.202 vs 0.290) in patients with relapsing multiple sclerosis.
 
Roche announced that in the 95 patient, Phase III, SAkuraStar trial, 76.1% of patients treated with satralizumab were relapse-free at 48 weeks, and 72.1% were relapse-free at 96 weeks compared to 61.9% at 48 weeks and 51.2% at 96 weeks with placebo in patients with NMOSD.
 
Ritter announced that in a 61-day, 557 patient, Phase III trial, treatment with RP-G28 was no more effective that placebo in reducing symptoms of lactose intolerance (abdominal pain, cramping, bloating and gas).
 
Published Research Updates
 
In the 24-month, 1,320 patient, Phase III RADIANCE trial, treatment with Celgene’s oral ozanimod resulted in an annualised relapse rate of 0.17 with 1 mg and 0.22 with 0.5 mg compared to 0.28 with weekly intramuscular interferon beta-1a 30 mcg in patients with relapsing multiple sclerosis. 
 
In a 12-week, 249 patient, Phase II trial, 22.6% of patients that received Lilly’s mirikizumab 200 mg achieved remission compared to 4.8% with placebo in patients with moderate-to-severe active ulcerative colitis.
 
The 230 patient, Phase III N-MOmentum trial was stopped early due to a clear demonstration of efficacy where treatment with Viela Bio/AstraZeneca’s inebilizumab resulted in 12% of the cohort experiencing aneuromyelitis opticaspectrum disorder (NMOSD) attack compared to 39% with placebo in patients with NMOSD.
 
In a 180-day, 260 patient, Phase III trial, treatment with Mesoblast’s remestemcel-L did not improve the complete resolution of aGvHD symptoms for at least a 28 day period compared to placebo (35% vs 30%) in patients with steroid refractory aGvHD.
 
In the 339 patient, Phase II, open-label, TRINITY trial, treatment with AbbVie’s rovalpituzumab resulted in an overall response rate of of 12.4% (with 14.3% in DLL3-high and 13.2% in DLL3-positive patients)and a median overall survival of 5.6 months in patients with DLL3-expressing small cell lung cancer in the third-line and beyond (3L+) setting.The drug has an Orphan Drug Priority Designation.
 
In a 12-week, 71 patient, open-label trial, treatment with LGLife Sciences/Sanofi’s gemigliptin resulted in a 27.2 point decrease in the mean amplitude of glycemic excursions compared to a 7.9 point decrease with dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone or drug naive.
 
In a 9.8-month, 70 patient, Phase II, open label, Chinese trial, treatment withBeiGene’stislelizumab resulted in an overall response rate of 87.1%, a complete response in 62.9% and a 9-month progression free survival rate of 74.5% in patients with relapsed or refractory Hodgkin's lymphoma.