The FDA designated TG Therapeutics’ umbralisib with breakthrough status for the treatment of marginal zone lymphoma. Umbralisib had previously been designated an orphan drug.
The FDA has put a partial hold on an axalimogene filolisbac Phase III cervical cancer trial, until Advaxis provides additional chemistry, manufacturing and controls information. Under the hold, no new patients can be enrolled in the trial, but current patients can continue to be treated.
Pfizer is seeking approval for tafamidis to treat transthyretin amyloid cardiomyopathy (ATTR-CM). Patisiran and inotersen were approved in 2018 for the treatment of hereditary transthyretin familial amyloid polyneuropathy (hTTR-FAP). Both drugs are seeking to broaden their approval to other TTR amyloidosis diseases.
In a 9-day, 48 patient, Phase I trial, Eisai/Purdue’s lemborexant did not impair driving ability compared to placebo as measured by the standard deviation of lateral position in the morning after a bedtime dose.
In an 1,856 patient, Phase III trial 77.9% of patients treated with Lilly’s lasmiditan, who had one or more cardiovascular risk factors but had not developed cardiovascular disease suggesting that cardiovascular risk is not increased with lasmiditan.
In a 77-patient long term follow-up of the Phase II, open-label, Arades trial, the median time to PSA progression was 25.2 months with Bayer/Orion Pharma’s darolutamide, in men with progressive metastatic castration-resistant prostate cancer.
GeNeuro announced the generic name for GNbAC1 is temelimab.
In a 14-week, 834 patient, Phase III, dose ranging trial, patients treated with the highest dose of Daiichi Sankyo’s mirogabalin (30 mg) reduced a pain score compared to placebo in Asian patients with type 1 or 2 diabetes and diabetic peripheral neuropathic pain.
MacroGenics announced interim results from a 55 patient, Phase II, open label trial, where treatment with margetuximab plus pembrolizumab resulted in an overall response rate of 32.7% and progression-free survival of 4.7 months in patients with relapsed or refractory advanced HER2+ gastric carcinoma.
ChemoCentryx submitted an MAA for avacopan in Europe in early 2018, but then withdrew the application in early 2019. ChemoCentryx plans to submit and MAA and NDA for avacopan in 2020 based on data from the Phase III ADVOCATE trial that is expected to be available in late 2019. The ADVOCATE trial will compare avacopan to predinisone for the induction of remission in patients with ANCA-Associated Vasculitis that are also receiving cyclophosphamide, rituximab and azathioprine.
In a Phase III trial, treatment with Proteon Therapeutics’ vonapanitase did not reduce thrombosis occurrence or corrective procedures (primary fistula patency) compared to placebo in hemodialysis patients with a new arteriovenous fistula.
Anuria announced that in a Phase II trial, patients treated with voclosporin ophthalmic drops did not have less discomfort than patients treated with cyclosporine ophthalmic emulsion (Restasis) in patients with dry eye syndrome. In this trial, voclosporin ophthalmic drops did demonstrate better efficacy (secondary endpoints) as measured by Schirmer Tear Test/STT (an objective measure of tear production), and Fluorescein Corneal Staining/FCS (an objective measure of structural damage to the cornea).
The FDA approved 59 investigational drugs to be released to distribution in 2018, beating the 2017 total of 46. The number of approvals in 2018 also sets a record for the number of new drug approvals in a single year. The previous highest annual total was 53 in 1996.
Almost 3/4 of the drugs (43) had priority reviews. Almost half of the priority reviews were filed as orphan drugs (34), while 58% were for rare diseases, 41% had Fast Track status and almost a quarter were designated as Breakthrough Therapies (14). Through its work in streamlining and optimizing drug reviews, 71% of drugs were first approved in the U.S. All drugs were approved by or before their PDUFA dates.
The FDA was not the only one that increased the number of new drugs approved in 2018. The European Medicine Agency approved 42 new drugs last year, which is up from 35 in 2017. This included 21 drugs that were designated Orphan Drugs. As in the U.S., the largest therapeutic group were the 23 oncology drugs approved.
Congress passed Right-To-Try legislation in the spring of 2018. Formal guidelines have not been announced, but ERC-1671 (Gliovacfrom Epitopoietic Research Corp)became the first right to try drug in the fall.
Notable approvals in 2018
A total of 14 infectious disease drugs that included:
Medscape's Review of New Drug Approvals
The FDA's 2018 Drug Therapy Approvals
The FDA's List of 2018 Drug Approvals by Medical Specialty
PM Live's Review of European 2018 Drug Approvals
Specialty Pharmacy Time's Review of Top Ten Specialty Pharmaceutical Approvals
According to Forbes “While the FDA is continuing to carry out reviews funded by fiscal year (FY) 2018 Prescription Drug User Fee Act user fees, including the review and approval of new drugs and biologics funded by carryover user fee balances, the agency is not accepting FY 2019 user fees until funding appropriations have been authorized, i.e., the political impasse has been resolved. Consequently, the FDA has suspended reviews of existing Investigational New Drug (IND) and Biologics License Application (BLA) applications not covered by user fees and is not reviewing applications for new drugs and biologics submitted during the shutdown period, except for emergency INDs and BLAs. The FDA is also not reviewing medical device applications submitted during the lapse period. And, the FDA is curtailing work on regulatory guidance documents pertaining to medical devices, drugs, and biologics.”
FDA Actions in spite of the shutdown…
The FDA has accepted two NDAs from Pfizer on 1/14/19 for tafamidis. Tafamidis meglumine was granted a priority review with a July 2019 PDUFA date and the free acid of tafamidis will receive a standard review with a November 2019 PDUFA date. Tafamidis meglumine requires four 20 mg capsules for a dose, while 61 mg of the free acid will be available as a single capsule.
The FDA granted serlopitant Breakthrough Therapy status in January 2019.
The FDA Bone, Reproductive and Urologic Drugs Advisory Committee voted 18-1 to recommend approval of romosozumab on 1/17/2019, but also recommended a boxed warning for cardiovascular safety.
The FDA rejected sacituzumab govitecan on 1/17/2019 due to problems with manufacturing the drug.
Eisai and Purdue Pharma submitted an NDA for lemborexant in January 2019.
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 on 1/17/2019. Some members of the committee expressed concern regarding the increased risk for diabetic ketoacidosis with the drug.
In a 52-week open label extension of a Phase III idalopirdine trial, no beneficial effects were seen. Idalopirdine was safe and well tolerated when added to donepezil, and memantine.
In a 2-year, 86 patient, Phase II, open label, single arm, Chinese trial, treatment with zanubrutinib resulted in an overall response rate of 83.5% with a progression free survival in 82% of patients with Mantle Cell Lymphoma.
An evaluation of data from the STRATOS 1 and 2 trials suggested there was no risk of severe hypersensitivity or anaphylactic reactions with tralokinumab.
In a 138-patient trial, treatment with udenafil decreases postmicturition dribbling in healthy men with a mean age of 57.6 years.
Phase III data identified an increased risk for stroke that caused Merck to discontinue development of odanacatib.
In a 6-month, 38 patient Phase I/II trial, treatment with voxelotor increased hemoglobin and reduced hemolysis in patients with sickle cell disease.
There are two investigational drugs with January 2019 PDUFA dates. We note two drugs scheduled for January reviews and highlight drug development for Alzheimer’s.
Immunomedics, Seattle Genetics’ sacituzumab govitecan has a PDUFA date of January 18th. It is an antibody-drug conjugate targeting triple-negative breast cancer. Immunomedics is seeking approval for the treatment of metastatic triple-negative breast cancer in patients that have previously received at least two prior therapies for metastatic disease.
Alkermes’ samidorphan buprenorphine has a PDUFA date of January 31st. The drug has a Fast Track priority designation. However, The FDAs Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Committee voted 21-2 against recommending approval of buprenorphine/samidorphan in a joint meeting in November 2018. The committee felt that efficacy had not been proven and studies had methodological problems, but in a narrow vote (13-10) indicated that safety had been demonstrated.
The FDA's Endocrinologic and Metabolic Drugs Advisory Committee will review Lexicon Pharmaceuticals/Sanofi’s sotagliflozin in mid-January. The drug is a SGLT inhibitor for the treatment of type 2 Diabetes with a PDUFA Date of March 22,2019, and no Priority Designations.
The FDA's Reproductive and Urologic Drugs Advisory Committee review romosozumab in mid-January. Romosozumab is a monoclonal antibody investigational drug for the treatment of osteoporosis by inhibiting the action of sclerostin. On July 17th, 2017, the FDA rejected romosozumab. This decision was expected because of the higher rate of serious adverse cardiovascular events when compared with alendronate. Amgen and UCB refiled an NDA for romosozumab in July 2018.
As we highlighted in our weekly update on January 8th, Evaluate.com’s Vantage 2019 Preview noted that a potentially very valuable but elusive therapy area for 2019 is Alzheimer’s disease, and this year will undoubtedly contain updates. We list 23 investigational drugs for Alzheimer's disease in our knowledgebase. None of the drugs have 2019 PDUFA Dates.
It has been debated whether potential treatments would be more effective if used before development of symptoms in Alzheimer's Disease. Studies in early stages of the disease have not been successful, so the drugs may need to be tested in patients at risk of developing the disease. To address this issue, the FDA has proposed that if reliable biomarkers can be developed to diagnose Alzheimer’s before the onset of subtle cognitive or functional changes, these biomarkers could be used as surrogate endpoints for the approval of a new drug. Since there are no accepted biomarkers for Alzheimer’s Disease, the FDA has encouraged researchers to develop them.
As we roll into 2019, we highlight some trends to watch. Additional detail available at Evaluate.com’s Vantage 2019 Previewfor an industry-wide analysis.
As we highlighted in our 2018 updates another potentially very valuable but elusive therapy area is Alzheimer’s disease, and next year will undoubtedly contain updates. We list 23 investigational drugs for Alzheimer's disease in our knowledgebase.
Regarding upcoming potential budget busters, there are fifteen investigational drugs with PDUFA Dates between January and Sept 2019. Eight of these drugs have priority designations. Take a look at our “Monitoring Drugs with PDUFA Dates” Use Caseto see how the Prescribe Right Pharmaceutical Pipeline Tracker can keep you on top of these drugs.
And from the week ending January 5, 2019:
We added 20 more drugs to the database and 17 more citations. The Pharmaceutical Pipeline Tracker now features comprehensive, unbiased, actionable information on 643 investigational drugs including URL links directly to 874 citations.
The FDA accepted the NDA for Acer Therapeutics’ celiprolol (Edsivo) on 12/26/2018 and set a PDUFA for 6/25/2019.
300mg of anifrolumab from Medarex and MedImmune, AstraZeneca in a Phase IIb trial, the primary endpoint of the SLE Responder Index (SRI-4) response with reduction in corticosteroid dose at 24 weeks was 34.3% compared to 17.6% with placebo in adult patients with moderate-to-severe systemic lupus erythematosus. The 1000 mg anifrolumab dose was no different than placebo. At 52 weeks, the SRI-4 was 51.5% with anifrolumab 300 mg, 38.5% with 1000 mg and 25.5% with placebo. A post-hoc analysis suggested an improvement in rash and arthritis symptoms at 52-weeks.
In a 153 patient, Phase II trial, treatment with Genentech and Array BioPharma’s ipatasertib added to mFOLFOX6 did not improve progression-free survival compared to mFOLFOX6 alone in all patients or in patients who were phosphatase and tensin homolog (PTEN)-low with locally advanced or metastatic gastric/gastroesophageal junction cancer.
In an 86 patient Indian study, a continuous infusion of Mallinckrodt and Biovie's terlipressin, 4.7% of portal hypertension patients with acute variceal bleeding experienced treatment failure compared to 20.7% with placebo.
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