Prescribe Right Pharmaceutical Pipeline Update for September 20

Update on investigational drugs with recent and upcoming PDUFA dates:

• The FDA approved Teva’s fremanezumab (Brand name: Ajovy) for the prevention of migraines, on 9/14/18, two days ahead of its PDUFA date. Fremanezumab will be available in pre-filled syringes dosed as 225mg monthly or 675mg (3 x 225mg doses) every 3 months. Teva has set the Wholesale Acquisition Cost (WAC) at $575 per syringe. A coupon program to reduce the co-pay is also being launched. The drug had a Fast Track Priority Designation.
• Jazz announced that in patients with narcolepsy or obstructive sleep apnea, solriamfetol-treated patients in Phase III Trials had an improvement in wakefulness and a decrease in sleepiness compared to placebo. Jazz also announced a subset of 280 patients participated in a 2-week withdrawal trial, where patients switched from solriamfetol to placebo had a decrease in wakefulness and an increase in sleepiness. PDUFA date Dec 20, 2018, Orphan Drug Priority Designation.
• Acacia Pharma’s amisulpride for post-operative nausea and vomiting, has a PDUFA date of 10/5/18. Trade name: Barhemsys

Plus news about nine other drugs in development:
In a Phase II trial, bimagrumab (Novartis) treated patients with sporadic inclusion body myositis had an increase in thigh muscle volume, but not 6-minute walk distance. Bimagrumab has a Breakthrough Therapy Priority Designation.

Patients with rheumatoid arthritis that had achieved sustained control with 4 mg baricitinib (Lilly, Incyte) when given a reduced dose of 2mg showed a low disease activity rate in 67% vs 80%, remission in 33% vs 40%, relapse in 37% vs 23% and need for rescue medication in 18% vs 10%.

 In a Phase III trial, postmenopausal women were treated with romosozumab (Amgen, UCB) or placebo for 1 year, then denosumab for 2 years. After 36 months 1% of romosozumab patients had a vertebral fracture compared to 2.8% with placebo. In another Phase III trial, patients were treated with either romosozumab or alendronate for one year, then all patients received alendronate for an additional year. After 24 months. romosozumab patients had an incidence of vertebral and clinical fractures of 6.2% and 9.7% compared to alendronate patients’ incidence of 11.9% and 13%. In a complicated extension trial with multiple treatment combinations, there was evidence to suggest further increase in BMD, in patients that received 12 months of denosumab after receiving 24 months of romosozumab. In a 245 male patient, Phase III trial, romosozumab increased BMD in the spine and hip compared to placebo in men with osteoporosis. 

In a Phase III trial, more patients with moderate-to-severe rheumatoid arthritis treated with filgotinib (Galapagos, Gilead) 200 mg achieved AR20 (69 vs 55%), AR50 (46 vs 35%) and AR70 (32 vs 20%) vs placebo.

In a 12-week, dose ranging, Phase II trial, of patients with moderate-to-severe psoriasis, treatment with daily doses of BMS-986165 resulted in lower Psoriasis Area and Severity Index score than placebo.

Multiple updates for risankizumab (AbbVie, Boehringer Ingelheim):

•  In Phase II trial, 24% to 37% of patients with Crohn’s Disease treated with risankizumab reached remission (CDAI score < 150) compared to 15% with placebo. 
• In a Phase II trial, 77% of patients with moderate-to-severe plaque psoriasis, treated with risankizumab had a 90% reduction in their PASI compared to 40% treated with ustekinumab. After 9 months, 69% of patients with moderate-to-severe plaque psoriasis maintained clear or almost clear skin in the higher dose risankizumab group compared to 30% of patients in the placebo group. 
• In a Phase III, 75% of risankizumab treated patients achieved PASI 90 compared to 42% treated with ustekinumab and 5% with placebo in patients with moderate-to-severe chronic plaque psoriasis. 
• In a Phase III trial, of patients with moderate-to-severe chronic plaque psoriasis, 75% of risankizumab-treated patients achieved PASI 90 compared to 47% treated with ustekinumab and 2% with placebo. Pooled data from trials found that at 12-months, 56% of patients treated with risankizumab reported being symptom free measured with the patient reported psoriasis symptom scale (PSS) compared to 30% with ustekinumab. 
• In another Phase III trial, 72% of risankizumab-treated patients achieved PASI 90 compared to 47% treated with adalimumab. 
•  A presentation at ACR 2017 described 16-week results from a Phase II psoriatic arthritis trial where 60% of risankizumab patients achieved ACR20 compared to 36% with placebo. A reduction in psoriatic arthritis severity as measured by PASI75 was achieved in 67%-75% of risankizumab patients compared to 10% with placebo. 
•  In a Phase III trial of patients with active ankylosing spondylitis, patients treated with risankizumab did not have at least a 40% improvement in the Assessment in SpondyloArthritis International Society (ASAS40) compared to placebo.
• In a Phase III trial, Vital Therapies’ VTL C3A, with an Orphan Drug Priority Designation, failed to demonstrate a benefit in survival compared to placebo in patients with severe alcoholic hepatitis.

Multiple updates for upadacitinib (AbbVie):

• AbbVie announced that in a phase II trial, upadacitinib, with a Breakthrough Therapy Priority Designation, reduced endoscopic remission in Crohn's patients more than placebo. 
• In a Phase III trial of patients with moderate-to-severe rheumatoid arthritis that had an inadequate response to conventional DMARDs, ACR20 was achieved by 64-66% of patients for the 15 mg and 30 mg doses of upadacitinib compared to 36% with placebo. 
• AbbVie announced that in a Phase III trial, complete remission was reached by 41% of rheumatoid arthritis patients that received upadacitinib 30 mg compared to 8% continuing on methotrexate. 
• AbbVie announced that in a Phase III trial, ACR20 was achieved by 71% of rheumatoid arthritis patients that received upadacitinib compared to 63% on adalimumab and 36% on placebo. Clinical remission was reached by 71% in upadacitinib patients compared to 29% on adalimumab and 14% on placebo. 
• AbbVie announced interim results at 32 weeks in a Phase IIb trial, where patients with moderate or severe atopic dermatitis patients treated with upadacitinib had a 48% (7.5mg dose), 44% (15mg dose) and 68% (30mg dose) improvement in their Eczema Area and Severity Index score compared to 34% with placebo. 
• AbbVie announced that in a Phase III trial, ACR50 was achieved by 60-66% of rheumatoid arthritis patients that received upadacitinib compared to 33% that received methotrexate.​

Karyopharm announced that in a Phase IIb trial, treatment with selinexor in combination with dexamethasone resulted in a 26% overall response rate and a median survival of 8.6 months in patients with highly resistant multiple myeloma. Karyopharm initiated a rolling NDA in July 2018 and plans to file an MAA in early 2019. Selinexor is also being studied in combination with bortezomib in the treatment of resistant multiple myeloma. Karyopharm has an ongoing Phase III study evaluating selinexor, combined with bortezomib and dexamethasone in the treatment of resistant multiple myeloma with topline results available in 2019. Selinexor has an Orphan Drug Priority Designation.

Colucid announced a study of 1,545 migraine patients, in which 28-32% of patients treated with lasmiditan were migraine pain-free at 2 hours compared to 15% with placebo and 41% had resolution of their most bothersome symptoms vs 30% with placebo.
Lilly announced that in a Phase III trial, 31-39% of patients with an acute migraine treated with lasmiditan were pain-free at 2 hours compared to 21% with placebo. 44-49% of lasmiditan patients were free of their most bothersome symptoms at 2 hours.
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You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker.