FDA Drug Approvals

Complete response letter

Dihydroergotamin (Levadex, Allergan) inhalation aerosol for the acute treatment of migraines in adults. In addition to the response, the company has already received draft labeling from FDA. Allergan anticipates minimal revisions to this labeling. 

The main issues cited in the complete response letter (CRL) were already identified by FDA in prior discussions with Allergan. The company has already taken the following actions to address these concerns: (1) Per FDA’s comments in the CRL, during a previous inspection, the agency noted concerns with Exemplar Pharma, LLC, the canister filling unit manufacturer. In accordance with Allergan’s overall manufacturing strategy to secure its supply chain, Allergan completed the acquisition of Exemplar on April 12th, 2013, for less than $20 million. Allergan has appointed senior members of Allergan’s Global Technical Operations to oversee the facility. Allergan anticipates that FDA will require a re-inspection of the Exemplar facility prior to approval; (2) FDA also noted concerns regarding the manufacturing process for the final filled canisters. Allergan has already responded to this concern. As FDA indicated in the CRL, the Agency has not yet reviewed Allergan’s response under the current PDUFA timeline.

APF530  (A.P. Pharma) for preventing chemotherapy-induced nausea and vomiting. The complete response letter (CRL) describes the following issues that must be addressed: (1) With respect to chemistry, manufacturing and controls (CMC), FDA has requested the refinement of one product quality analytical test method, and that certain deficiencies identified during facility pre-approval inspections be addressed; (2) FDA has requested that a human factors validation study evaluating the usability of the APF530 syringe system together with its proposed product labeling and instructions for use be conducted with product assembled using a validated, commercial process; (3) With respect to clinical, FDA has requested a re-analysis of the existing phase 3 clinical data that reclassifies patients into those receiving moderately emetogenic chemotherapy and highly emetogenic chemotherapy according to the recently modified ASCO 2011 Guideline. FDA did not request any new clinical studies.

Treprostinil diolamine extended-release tablets (oral treprostinil) (United Therapeutics) for the treatment of pulmonary arterial hypertension. This is United Therapeutics’ second complete response letter (CRL) and it intends to immediately request an end-of-review meeting with FDA to discuss the CRL.

Pandemic Influenza A Virus Monovalent Adjuvanted candidate vaccine (Q-Pan H5N1, GlaxoSmithKline) for active immunization for the prevention of disease in adults aged 18 years and older who are at increased risk of exposure to the H5N1 influenza virus subtype contained in the vaccine. The Complete Response letter was triggered due to an administrative matter that has recently been rectified. GSK and FDA are actively working together to complete the review in a timely manner. 

Priority review

Riociguat (Bayer) for the treatment of 2 distinct forms of pulmonary hypertension, (inoperable chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension).

Fast-track designation

Daratumumab (Genmab A/S) for patients with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory (IMiD) agent, or are double refractory to a PI and an IMiD.

FDA actions in brief

Updated labeling for reformulated oxycodone hydrochloride controlled-release (OxyContin, Purdue Pharma) tablets was approved. The new labeling indicates that the product has physical and chemical properties that are expected to make misuse and abuse via injection difficult and to reduce abuse via the intranasal route.

Supplemental new drug application (sNDA) for lubiprostone (Amitiza, Sucampo Pharmaceuticals and Takeda Pharmaceuticals) 24 μg twice daily was approved as the first oral medication for the treatment of opioid-induced constipation in adult patients with chronic, noncancer pain.

Brinzolamide 1.0% and brimonidine tartrate 0.2% (Simbrinza Suspension, Alcon, a division of Novartis) was approved for the reduction of intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension.

Norethindrone acetate and ethinyl estradiol capsules and ferrous fumarate (Minastrin 24 FE, Warner Chilcott) capsules were approved for the prevention of pregnancy.

Carbinoxamine maleate extended-release oral suspension (Karbinal ER, Tris Pharma), the first sustained-release histamine receptor blocking agent was approved for the treatment of seasonal and perennial allergic rhinitis in children aged 2 and up.

Rabeprazole sodium (AcipHex Sprinkle, Eisai) Delayed-Release capsules 5 mg and 10 mg were approved for the treatment of gastroesophageal reflux disease (GERD) in children ages 1 to 11 years of age for up to 12 weeks.

Levonorgestrel/ethinyl estradiol and ethinyl estradiol (Quartette, Teva) tablets were approved for the prevention of pregnancy.

Dimethyl fumarate (Tecfidera, Biogen Idec) capsules were approved for the treatment of adults with relapsing forms of multiple sclerosis.

Doxylamine succinate 10 mg, pyridoxine hydrochloride 10 mg (Diclegis, Duchesnay) delayed-release tablets were approved for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management, including dietary and lifestyle modifications.

A .07% formulation of bromfenac (Prolensa, Bausch + Lomb) was approved for the treatment of postoperative pain associated with cataract surgery. It will likely replace the 0.9% bromfenac ophthalmic solution.

Orphan drug designations

ACE-536 (Celgene and Acceleron) for the treatment of 2 rare blood disorders: beta-thalassemia and myelodysplastic syndrome.