August Summary of FDA Regulatory Actions

Summary: In a busy August, the FDA approved seven new investigational drugsfor the marketplace,twice the monthly average of approvals for the first half of 2019. Four drugs in the Pharmaceutical Pipeline Tracker received new FDA Priority Designations. Two drugs hit bumps in the road with one rejection and one PDUFA Date delay. Seven drugs were involved with new NDA and BLA submissions. Finally, we’ve included two notable other developments. Read on.
​
Regulatory Approvals

1. The FDA approved istradefylline (Nourianz, Kyowa Kirin) on 8/27/2019 for the treatment of off episodes in adults with Parkinson's disease already receiving levodopa/carbidopa.
2. The FDA approved both oral and intravenous formulations of lefamulin (Xenleta, Nabriva Therapeutics) on 8/19/2019 for the treatment of community-acquired pneumonia. The WAC price per day for the IV dose is $205 and the oral dose is $275 per day.
3. The FDA approved pretomanid (TB Alliance) on 8/14/2010 in conjunction with bedaquilineand linezolid for the treatment of adults with extensively drug-resistant, treatment-intolerant, or nonresponsive multidrug-resistant tuberculosis.
4. The FDA approved pitolisant (Wakix, Harmony Biosciences) on 8/15/2019 for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy.
5. The FDA approved entrectinib (Rozlytrek, Roche) on 8/15/2019 for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC). Roche set the monthly WAC at $ $17,050 for the drug.
6. The FDA approved fedratinib (Inrebic, Celgene, Bristol-Myers Squibb) on 8/16/2019 for the treatment of primary or secondary myelofibrosis classified as either intermediate-2 or high risk. Fedratinib was approved with a Boxed Warning regarding a risk of serious and potentially fatal brain damage or dysfunction.
7. The FDA approved upadacitinib (RINVOQ, AbbVie) on 8/16/2019 for the treatment of adults with moderately to severely active rheumatoid arthritis with an inadequate response or intolerance to methotrexate. AbbVie set the annual WAC at $59,000 for the drug.

FDA Priority Designations

1. The FDA granted Fast Track status to Moderna’s investigational Zika vaccine, mRNA-1893.
2. The FDA designated teplizumaba Breakthrough Therapy Designation for the prevention or delay of clinical type 1 diabetes in patient at risk of developing the disease.
3. The FDA designated elafibranor an orphan drug for the treatment of primary biliary cholangitis.
4. The FDA designated bempegaldesleukin in combination with nivolumab as a Breakthrough Therapy for initial treatment of unresectable or metastatic melanoma.

Rejections, Withdrawals and Delays

1. The FDA rejected Sarepta Therapeutics' golodirsen (Vyondys 53) for the treatment of Duchenne muscular dystrophy amenable to exon 53 skipping due to the risk of infection with intravenous infusion ports and renal toxicity seen in pre-clinical studies. Sarepta has shown that golodirsen will increase dystrophin levels, but has not completed studies to demonstrate an improvement in muscle function.
2. After canceling an advisory committee meeting to review lumateperonedue to new information provided for the NDA, the FDA delayed the PDUFA date for 3 months to 12/27/2019.

New NDAs, BLAs and a Re-submission

1. The FDA accepted the NDA for VX-445 (elexacaftor, tezacaftor and ivacaftor) for the treatment of cystic fibrosis in patients with one F508del mutation and one minimal function mutation or two F508del mutations. A PDUFA date has been set for 3/19/2020.
2. The FDA accepted the NDA for givosiran for the treatment of acute hepatic porphyria and set a PDFUA date of2/4/2020.
3. The FDA accepted the NDA for avapritinibfor the treatment of PDGFRA Exon 18 mutant gastrointestinal stromal tumors and set a PDFUA date of 2/14/2020.
4. Ultragenyx has submitted an NDA for the use of triheptanoin in the treatment of long-chain fatty acid oxidation disorders.
5. DBV resubmitted a BLA in August 2019, for Viaskin Peanut for the treatment of peanut-allergic children after having withdrawn its original BLA for the Viaskin peanut allergy transdermal patch in 2018 due to FDA concerns about its manufacturing process.
6. The FDA accepted the BLA for zanubrutinib for the treatment of mantle cell lymphoma and assigned a PDUFA date of 2/27/2020.
7. Celgene plans to submit a BLA for lisocabtagene maraleucel for the treatment of multiple myeloma in the first half of 2020.

Other Developments

1. GSK licensed its Ebola vaccines to the Sabin Vaccine Institute. Sabin has signed an agreement with the National Institute of Allergy and Infectious Diseases’(NIAID) Vaccine Research Center to develop the drug.
2. On 8/1/2019 Horizon Therapeutics initiated an FDA approved expanded access program for teprotumumab for up to 60 patients with active moderate to severe thyroid eye disease under ClinicalTrials.gov NCTnumber: NCT04040894. Physicians can request access to teprotumumab sending an e-mail to medicalinformation@horizontherapeutics.com. Horizon Therapeutics submitted a BLA for teprotumumab in July 2019.