Pipeline News and Updates
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Thirty-one citations were added to our knowledgebase bringing the total to 809. Each citation is accessible from the single drug look-up monograph via a URL link. There are now 612 investigational drugs in the Knowledgebase.
Two Updates on products with PDUFA Dates and/or Priority Designations The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended approval of Lilly’s galcanezumab. The FDA has Fast-Tracked the drug with a review date next week, September 30, 2018. J&J announced that in a 4-week, 346 patient, Phase III trial, esketamine nasal spray added to a new anti-depressant did not improve Montgomery-Asberg Depression Rating Scale (MADRS) total score compared to monotherapy with a new antidepressant in patients with treatment-resistant depression. No PDUFA date but the drug has a Breakthrough Therapy Priority Designation. Five additional updates:
You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker. Update on investigational drugs with recent and upcoming PDUFA dates:
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):
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. You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker. Update on investigational drugs with recent PDUFA dates:
The FDA rejected Sunovion Pharmaceuticals’ dasotraline on 8/31/18 and requested additional data on efficacy and tolerability of dasotraline for the treatment of ADHD. In a Phase III trial of 32 patients with heart failure and renal impairment, Orion Pharma’s levosimendan compared to dobutamine had similar increases in renal blood flow (22% and 26%, respectively), better glomerular filtration rate, and filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine. Biocryst announced topline results from the high dose cohort of the 95 patient, ZENITH-1 Phase II trial, where 64% of patients with Hereditary Angioedema, treated with BCX7353 had mild or no symptoms compared to 32% with placebo. BCX7353 reduced the need for rescue drugs by 32%. BCX7353 has a Fast Track Priority Designation but no PDUFA date. China approved fruquintinib (Chi-Med, Lilly) in Sept 2018 for the treatment of metastatic colorectal cancer. Bluebird Bio announced Interim results from the phase II/III Starbeam Study which demonstrated that 15 of 17 childhood cerebral adrenoleukodystrophy patients treated with Elivaldogene tavalentivec were free of major functional disabilities and no graft versus host disease almost 30 months after treatment. Twenty-nine patients had at least 4.2 months of follow-up and none had experienced grade 2 or higher acute graft-versus-host disease. The drug has a Breakthrough Therapy Priority Designation but no PDUFA date. After failure in the CONCERTO and ARPEGGIO trials, Teva stopped development of laquinimod for multiple sclerosis. After the failure of a Phase II Huntington's disease trial, Teva ceased all development projects for laquinimod and returned all rights to Active Biotech. Gilead and Galapagos announced that in the 12-week, 116 patient Phase II, TORTUGA trial, patients treated with filgotinib had a 1.5-point decrease in their Ankylosing Spondylitis Disease Activity Score (ASDAS) compared to a 0.6 decrease with placebo. J&J has an ongoing Phase III trial testing esketamine for treatment-resistant depression and major depressive disorder with imminent risk of suicide. J&J filed an NDA for esketamine in September 2018 and plans to file an MAA before the end of 2018. Tezepelumab (AstraZeneca, Amgen) has been granted breakthrough status. No PDUFA date. You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker. September may be the month we see competition in the Anti-CGRP monoclonal antibody drug class. Two Investigational drugs in the Pharmaceutical Pipeline Tracker’s knowledgebase have PDUFA Dates during September. This will bring competition for erenunab (Aimovig), which was approved and launched in May. Both fremanezumab and galcanezumab are monoclonal antibodies that bind to calcitonin gene-related peptides.
Teva’s Fremanezumab with a PDUFA Date of September 16, 2018, due to its Fast Track status. It’s seeking approval for migraine prophylaxis. Teva's PDUFA date was delayed from June to September due to its API provider, Celltrion, receiving an FDA warning letter for manufacturing issues. Celltrion received a second warning letter from the FDA after a July 2018 inspection revealed problems with employee training quality control protocols. If the FDA delays the PDUFA date, it would potentially move fremanezumab to be the third approved product, instead of the second. In early September, Teva still felt the drug would be approved by the mid-September date. Lilly’s Galcanezumab with expected approval by the end of September 30, has Fast Track status for cluster headache. It’s indicated for migraine prophylaxis. Lilly plans to offer an auto-injector for galcanezumab like erenumab. Fremanezumab is a more viscous solution and will initially be offered as a prefilled syringe. So, while the drug may be approved as a quarterly subcutaneous injection, it may require a visit to a physician's office for administration, while monthly doses of galcanezumab and erenumab can be administered by the patient. Teva is working on an auto-injection system for fremanezumab, but it is not known when it will be available. One other Anti-CGRP monoclonal antibody investigational drug exists: Alder Biopharmaceuticals’ eptinezumab, which is administered every three months by IV infusion. Alder plans to file a BLA in the second half of 2018. Alder has the ongoing PROMISE-2 study involving chronic migraine patients. Erenumab is available as an auto-injector for monthly sub-Q injection. ICER released a final review of CGRP inhibitors on July 3, 2018. ICER found insufficient evidence to recommend erenumab or fremanezumab over oral preventative drugs or botulism toxin for prevention of migraine in untreated patients. ICER did find evidence of a benefit for use of erenumab or fremanezumab in patients that had previously failed preventative therapy for chronic migraine. Data was supportive but inconclusive for prevention of episodic migraine. ICER found insufficient evidence for use of galcabezumab in either indication. ICER estimated that CGRP inhibitors would improve quality of life years (QALY) for episodic and chronic migraine patients. The estimated cost per QALY were lower for chronic migraine compared to episodic migraine. ICER felt that insurers would be justified in setting limits or restrictions on CGRP inhibitors due to insufficient long-term safety data and high cost. With an announced WAC price of $6,900/year for erenumab, ICER estimates an annual cost of $5,000/year after discounts. ICER stated that a price of $3,700 to $5,300 per year to be cost effective. Erenumab or fremanezumab were found to be cost effective in QALY gained in patients that had failed at least one preventative therapy. Stay current with developments for drugs to reduce monthly migraines and all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker. Update on investigational drugs with recent PDUFA dates:
In other developments: In a Phase III trial, Pfizer’s tafamidis reduced all-cause mortality (30% vs 43%) compared to placebo. Tafamidis also reduced cardiovascular-related hospitalizations, decline in 6-minute walk test and decline in the Kansas City Cardiomyopathy Questionnaire–Overall Summary that measures health status. ADR were similar between tafamadis and placebo in the trial. Approved in the EU, it does not have PDUFA Date but does have Orphan Drug, Breakthrough Therapy, and Fast Track Priority Designations. Esperion announced that in a Phase III trial, in patients with atherosclerosis already receiving a high dose of statin, bempedoic acid and ezetimibe reduced LDL another 35% compared to 3% with placebo, 24% with ezetimibe monotherapy and 20% with bempedoic acid monotherapy. In a posthoc analysis of patients intolerant to statins, LDL was reduced 43% compared to 1% with placebo. In a 2,230 patient, Phase III trial, 13 patients (0.9%) that received bempedoic acid died compared to 2 (0.3%) in the placebo group. Esperion explains that 5 of the deaths were related to lung cancer. Esperion plans to price bempedoic acid < $4,000/ year. No morbidity or mortality results have been announced in bempedoic acid trials. No PDUFA date and no Priority Designations. A small study found that naltrexone reduces the antidepressant effects of intravenous ketamine, suggesting that opioid system activation is required for the antidepressant effect with ketamine. Since esketamine is a derivative of ketamine, this new data will affect how the drug is viewed for its place in therapy. AstraZeneca announced that in the 12-month Phase III trial, in patients with systemic lupus erythematous, anifrolumab did not reduce disease activity as measured by the SLE Responder Index, compared to placebo. AstraZeneca has another Phase III trial, ongoing evaluation of anifrolumab as a treatment for systemic lupus erythematous. Biogen announced that interim data from a Phase Ib trial suggest that after 3 years with a titrated dose and 4 years with a fixed dose, aducanumab (for Alzheimer’s disease) continued to show a reduction in amyloid plaque and a continued benefit on the rate of decline of the Clinical Dementia Rating Sum of Boxes (CDR-SB) and the Mini-Mental State Examination (MMSE). Ultragenyx may file an NDA for triheptanoin in late 2018 or 2019 with possible review in 2019. The drug has an Orphan Drug Priority Designation. Karyopharm announced that in the 122 patient, Phase IIb, STORM trial, treatment with selinexor resulted in a 25% overall response rate in patients with highly resistant multiple myeloma. In a Phase IIb trial, progressive multiple sclerosis patients treated with MediciNova’s ibudilast had 47% less brain atrophy (about 2.5 ml) compared to placebo. In a Phase II trial, treatment with capmatinib plus gefitinib demonstrated an overall response rate of 47% in patients with advanced c-MET-dysregulated non-small cell lung cancer (NSCLC). Among 161 patients in two early trials the most common adverse events with capmatinib were nausea, peripheral edema, decreased appetite, and rash. In a draft report, ICER estimated an annual cost of $24,700 and $46,488 for patisiran to be cost effective and $15,300 and $25,400 for inotersen to be cost effective. You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker. |
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