Allergan PLC's antipsychotic Vraylar became the 25th novel drug approved by FDA's Center for Drug Evaluation and Research in 2015. New submissions were plentiful, including a first-line claim for AbbVie Inc. and Johnson & Johnson's Imbruvica, and another breakthrough designation was awarded to Bristol-Myers Squibb Co.'s checkpoint inhibitor immunotherapy Opdivo.

Allergan Vraylar Clears FDA On Second Try

The atypical antipsychotic Vraylar (cariprazine) was approved on Sept. 17 to treat schizophrenia and acute manic or mixed episodes of bipolar I disorder in adults. The NDA was submitted in November 2012 by Forest Laboratories Inc., which is now part of Allergan after multiple mergers. Cariprazine was discovered by Gedeon Richter Ltd.

The sponsors conducted a new clinical trial after receiving a complete response letter in November 2013. Forest explained that the "complex pharmacokinetics and metabolism" of cariprazine was behind FDA's request that the company better define the dosing regimen ([A#14131121003]).

(The CDER Novel Approvals chart tracks new molecular entity and novel therapeutic biologic approvals for the year.)

Spiriva Becomes First Anticholinergic Approved For Asthma

Boehringer Ingelheim GMBH's Spiriva Respimat (tiotropium), a mainstay of chronic obstructive pulmonary disease treatment, added an indication for maintenance treatment of asthma in patients ages 12 years and older on Sept. 15. The approval makes Spiriva the first anticholinergic agent approved by FDA for asthma, BI noted ([A#00150921020]).

FDA's summary review of the Spiriva NDA notes that BI studied Spiriva with an earlier delivery device, the Handihaler, for asthma in the mid-1990s "with negative results." The new NDA, submitted Aug. 15, 2014, supplants those studies with data "results from studies that are large in size, longer in duration, and [required] all patients … to have persistent asthma and to be on [inhaled corticosteroid] maintenance treatment and other maintenance treatment appropriate for the disease severity."

Redactions in the summary review document suggest that BI also submitted another indication for Spiriva Respimat that was not approved.

Bristol's Opdivo Adds Fourth Breakthrough Therapy Designation

FDA designated Bristol's immunotherapy Opdivo (nivolumab) a breakthrough therapy for advanced or metastatic renal cell carcinoma – the checkpoint inhibitor's fourth breakthrough designation. Bristol said it plans regulatory submissions for RCC later in 2015.

The RCC breakthrough designation is based on data from the Phase III CheckMate-025 study, in which nivolumab demonstrated an overall survival benefit compared to everolimus, the standard of care for relapsed kidney cancer, in patients with previously treated clear-cell RCC. The trial was stopped early in July 2015 for efficacy.

(See the 'Breakthrough Therapy' chart on the FDA Performance Tracker for detailed information on products receiving the designation.)

AbbVie/J&J Seek To Move Imbruvica Use To Early Therapy For CLL

AbbVie and J&J announced the filing of an sNDA for the Bruton’s tyrosine kinase inhibitor Imbruvica (ibrutinib) in an earlier setting in chronic lymphocytic leukemia on Sept. 14. The sNDA seeks approval for treatment of newly diagnosed CLL patients aged 65 or older. Imbruvica is currently approved for two CLL populations: relapsed/refractory CLL and frontline treatment in hard-to-treat patients with 17p deletions.

The companies requested a priority review for first-line use in elderly patients. The company released positive Phase III data from the open-label RESONATE-2 trial in June, showing improvements in overall survival and progression-free survival in treatment-naïve patients treated with Imbruvica versus the chemotherapy chlorambucil ([A#14150914002]). The RESONATE-2 trial enrolled 269 treatment-naïve patients with CLL or SLL aged 65 and older. Patients were randomized to receive either ibrutinib 420 mg orally once daily until progression or unacceptable toxicity, or chlorambucil. The full data have been submitted for a presentation at an upcoming medical meeting and a peer-reviewed journal.

Novel Rx Treatment For Head Lice Submitted By Australian Firm

Australia's Hatchtech Pty. Ltd. announced the submission of a new molecular entity, Xeglyze (abametapir), on Sept. 14 as a prescription treatment of head lice infestation. Xeglyze, a metalloprotease inhibitor, has both ovicidal and lousicidal activity (killing the lice and eggs), Hatchtech said, while most pediculocides have little ovicidal effect. Xeglyze can thus be administered once, in a 10-minute application, while other lice treatments need two administrations.

The NDA is based on two Phase III trials that enrolled 704 patients. A single administration of Xeglyze produced an 81.5% success rate, the company said. Xeglyze, formerly known as DeOvo, will be commercialized in the U.S. by Promius Pharma LLC, a specialty pharma subsidiary of Dr. Reddy's Laboratories Ltd. Hatchtech developed the drug in collaboration with Dr. Reddy's Custom Pharmaceutical Services unit.

AAA's Somakit-Tate NDA Aims To Guide Treatment Of Neuroendocrine Tumors

FDA has granted a priority review to Advanced Accelerator Applications SA's NDA for Somakit-Tate, a radiopharmaceutical for diagnosis and management of somatostatin receptor-positive neuroendocrine tumors. The product is a pre-formulated kit used to radiolabel somatostatin analog peptides with the positron emitter 68-gallium Dotatate for use in PET scanning. The NDA was submitted July 1, the company said.

AAA ultimately plans to use Somakit to guide the use of its investigational candidate Lutathera, a lutetium-177-labeled somatostatin analog, in peptide receptor radionuclide therapy (PRRT) for carcinoid tumors.

(See the User Fee Goals chart on the FDA Performance Tracker for information on pending applications.)

Submission And More Submissions

The past week was a busy one for Keeping Track of new filings. Highlights include:

Baxalta Inc. submitted an application for a 20% concentration of subcutaneous immunoglobulin (IGSC 20%) for treatment of primary immunodeficiencies. Baxalta's IG Gammagard was originally available for I.V. administration; a 10% subcutaneous formulation of Gammagard was approved in 2011.
Amgen Inc. announced an sBLA submission on Sept. 11 for its recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor Repatha (evolocumab) allowing the 420 mg monthly dose of the LDL cholesterol-lowering drug to be administered as a single injection. Repatha's initial approval on Aug. 27, 2015 called for the 420 mg monthly dose for homozygous familial hypercholesterolemia to be administered as three injections given consecutively within 30 minutes.
Amgen announced Sept. 18 that its sNDA for its multiple myeloma therapy Kyprolis (carflizomib), seeking to expand the current indication to include use in combination with dexamethasone for patients who have received at least one prior therapy, had been assigned a priority review. The user fee goal date is Jan. 22, 2016. Kyprolis was recently approved for use with Revlimid (lenalidomide) and dexamethasone for patients with relapsed multiple myeloma who have received one to three prior lines of therapy, the company noted. The sNDA is based on the ENDEAVOR trial, in which Kyprolis/dex outperformed Velcade (bortezomib)/dex in a head to head comparison ([A#00150622010]).
Eisai Inc. announced FDA acceptance for review of its oral suspension formulation of the AMPA antagonist antiepileptic drug Fycompa (perampanel), which is marketed in tablet formulation. The oral suspension application was submitted June 30.
Vanda Pharmaceuticals Inc. announced a May 27, 2016 user fee goal for a maintenance therapy indication for its schizophrenia treatment Fanapt (iloperidone).
Medicure Inc. is asking FDA to approve Aggrastat (tirofiban) as the first glycoprotein IIb/IIIa inhibitor for treatment of ST elevation myocardial infarction (STEMI). The user fee goal for the antiplatelet agent for STEMI, administered as a high-dose bolus, falls in July 2016.

Keeping Track: Allergan Antipsychotic Vraylar Approved; First-Line Imbruvica Claim Submitted

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