Q1 2019 Review – Approvals, Rejections, Delays, Changes in Priority Review Status

Eight Approvals

• The FDA approved caplacizumab (Cablivi by Sanofi) on 2/6/2019 for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP).
• The FDA approved triclabendazole (Egaten from Novartis) on 2/13/2019 for the treatment of fascioliasis.
• The FDA approved turoctocog alfa pegol (Esperoct from Novo Nordisk) on 2/21/2019 for the treatment of hemophilia A, however due to a contractual agreement, the drug will not launch until 2020. Esperocot is a long acting version of NovoEight (turoctocog alfa).
• On 3/5/2019 the FDA approved esketamine nasal spray, in conjunction with an oral antidepressant, for the treatment of resistant depression. The labeling for esketamine nasal spray contains a Boxed Warning describing a risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors. The drug is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS). Esketamine must be administered in a certified medical office where the health care provider can monitor the patient for a minimum of 2 hours and determine when the patient can leave. The patient also needs transportation to and from the visit for a dose because they are unable to drive until the day after a dose. Since the patient cannot take the spray home, the treatment sites will need to determine where patients will wait during the monitoring period and coordinate patient visit to avoid a slowdown in office workflow. WAC for esketamine nasal spray is $590 to $885 per treatment session. The drug is dosed twice a week for the initial 4 weeks, so the monthly cost will be $4,720 to $6,785. Esketamine nasal spray is dosed once weekly during the second month ($2,360 to $3,540). In the third month the patient may continue weekly dosing or have their dosing further reduced to every other week, so the WAC price for maintenance dosing is $1,180 to $3,540.
• The FDA approved netarsudil and latanoprost ophthalmic solution (Rocklatan, Aerie Pharmaceuticals) on 3/13/2019 to decrease elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
• The FDA approved solriamfetol (Sunosi, Jazz Pharmaceuticals) on 3/20/2019 to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.
• The FDA approved brexanolone (Zulresso, Sage Therapeutics) on 3/19/2019 for the treatment of postpartum depression.
• The FDA approved siponimod (Mayzent, Novartis) on 3/26/2019 to treat adults with relapsing multiple sclerosis. In a draft review ICER felt that compared to best supportive care siponimod reduced the risk of disability progression and decreased inflammation. ICER analysis found that siponimod lowered the risk of relapse by 46% and had an annualized relapse rate of 0.07/year compared to 0.16/year with placebo. See our March 28th special update for more https://www.prescriberight.com/pipeline-news/fda-approves-siponimod-icer-weighs-in-and-april-pdufa-dates

Rejections

• The FDA rejected Motif Bio’s iclaprim due to concerns over liver toxicity and requested additional liver toxicity data. Iclaprim has Fast Track status and is designated a Qualified Infectious Disease Product by the FDA.
• The FDA followed an advisory panel recommendation and rejected ALKS 5461 (samidorphan plus buprenorphine) and requested additional efficacy data. Alkermes drug had a PDUFA date of 1/31/2019.
• The FDA rejected ferric maltol during Shield’s first submission, but the company has resubmitted an NDA, which was accepted by the FDA in December 2018 and assigned a PDUFA date of 7/27/2019. In a 36-week open label extension of the AEGIS-CKD trial, patients originally treated with ferric maltol maintained hemoglobin levels and patients switched from placebo demonstrated a similar rise in hemoglobin. 
• The FDA rejected sotagliflozin on 3/22/2019. Lexicon and Sanofi are working with the FDA to determine future development of the drug.

Changes in Priority Review Status

• 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 granted Daiichi Sankyo/Plexxikon’s pexidartinib breakthrough therapy and orphan drug designations and set a PDUFA date of 8/3/2019.
• The FDA designated AT-GAA as a Breakthrough Therapy in February 2019.
• The FDA has granted fedratinib a priority review, with a PDUFA date of 9/3/2019. There are now twenty-five investigational drugs with PDUFA Dates between March 14, 2019 and December 25, 2019
• The FDA removed the Breakthrough Therapy designation for oliceridine because current data did not support the designation. The FDA does feel the current safety data will support a refiled NDA after Trevena completes a Phase I safety study examining QT-interval prolongation.
• The FDA granted Orphan Drug status to Armetheon’s tecarfarin for the prevention of systemic thromboembolism of cardiac origin in patients with End Stage Renal Disease (ESRD) and Atrial Fibrillation (AFib).
• The FDA granted Qualified Infectious Disease Product (QIDP) to the oral and IV formulations of sulopenem in March 2019.  

Holds and Delays

• 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.
• On 2/28/2019, the FDA Oncologic Drugs Advisory Committee recommend a delay in approval of selinexor-dexamethasone to treat triple class-refractory myeloma until after the results of the Phase III BOSTON trial are available in the first half of 2020. An FDA review of selinexor found limited efficacy and significant toxicity in patients with relapsed/refractory multiple myeloma treated with a combination of selinexor dexamethasone. Based on data submitted and historical studies with high-dose dexamethasone, the FDA felt it was difficult to isolate the treatment effect of selinexor. 
• The FDA delayed a decision on NKTR-181 by three months to allow additional time to review preclinical data from two additional studies and set a new PDUFA date of 8/29/2019.
• In March 2019, the FDA delayed the PDUFA date for Karyopharm Therapeutics’ selinexor by three months (from April 6, 2019 to July 6, 2019).

New NDAs and BLAs

• The FDA accepted an NDA for diroximel fumarate on 2/25/2019 suggesting a PDUFA date of 12/25/2019.
• The FDA has accepted the BLA for entrectinib, which suggests a PDUFA date of August 18, 2019.
• The FDA has accepted the BLA for polatuzumab, which suggests a PDUFA date of August 19, 2019.
• The FDA has accepted the NDA for upadacitinib, which suggests a PDUFA date of August 19, 2019.
• The FDA has accepted the NDA for oral and IV lefamulin, which suggests a PDUFA date of August 19, 2019.
• The FDA accepted the NDA for Bioproject Pharma’s pitolisant on 2/12/2019, which suggests a PDUFA date of 8/12/2019. Pitolisant has both Fast Track and Breakthrough Therapy status.
• The FDA accepted the NDA for Sarepta Therapeutics’ golodirsen on 2/14/2019 and set a PDUFA date of 8/19/2019.
• The FDA accepted the NDA for ubrogepant on 3/11/2019. Allergan expects a 4Q19 PDUFA date of 12/27/19
•  The FDA accepted the NDA for lemborexant on 3/11/2019. Allergan expects a 4Q19 PDUFA date of 12/27/19