December Approval Review and January Preview

Regulatory Update

The FDA approved seven new drugs during December 2019, bringing the total new approvals for the year to forty-four. During the month the agency took another nineteen actions. 
There are two investigational drugs with PDUFA Dates in January: Aimmune Therapeutics’ AR101 for Peanut Allergy and Epizyme’s Tazemetostat for Epithelioid sarcoma. AR101 has three FDA Priority Designations: Orphan Drug, Breakthrough Therapy, and Fast Track.

For a complete review of January’s potential blockbusters order Prescribe Right’s Pharmacy & Therapeutics Committee Forecast (PDF document and slides). The current forecast coverage period is January 1, 2020 through March 31, 2020. 
Each forecast contains a review of investigational drugs with PDUFA Dates during each calendar quarter. Contents include generic name, brand name (if available), mechanism of action, ADRs, route, indication(s), PDUFA Date, FDA Priority Designations (if any), efficacy and a general comment from our Founder and CEO Scot Walker, PharmD, MS, BCPS, BCACP.
Click here for ordering details
​
Seven New December Approvals

1. The FDA approved for lemborexant (Dayvigo, Eisai) on 12/23/19 for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
2. The FDA approved lumateperone (Caplyta, Intra-Cellular Therapies) on 12/23/19 for the treatment of schizophrenia in adults. Lumateperone has a boxed warning due to an increased risk of death for elderly patients with dementia-related psychosis. The label also contains a warning for increased risk for cerebrovascular events in this population.
3. The FDA approved ubrogepant (Ubrelvy, Allergan) on 12/23/19 for the acute treatment of migraine with or without aura in adults.
4. The FDA approved trastuzumab deruxtecan (Enhertu, AstraZeneca/Daiichi Sankyo) on 12/19/19, for the treatment of unresectable or metastatic HER2-positive breast cancer that has received two or more prior anti-HER2-based regimens in the metastatic setting.
5. The FDA approved Merck’s Ebola virus vaccine (Ervebo) on 12/20/19, for the prevention of Ebola virus disease caused by the Zaire ebola virus in people at least 18 years old.
6. The FDA approved enfortumab vedotin (Padcev, Astellas/Seattle Genetics) on 12/18/19 for the treatment of locally advanced or metastatic urothelial cancer that has progressed on chemotherapy and immunotherapy.
7. The FDA approved golodirsen (Vyondys 53, Sarepta Therapeutics) on 12/12/2019 for the treatment of Duchenne muscular dystrophy amenable to exon 53 skipping. We took a look at this surprise reversal of the August 2019 rejection of the drug in a post last week.

Nineteen Other FDA Actions 

1. The FDA rejected ViiV Healthcare/Janssen’s NDA for the combination of cabotegravir and rilpivirine for HIV treatment, due to manufacturing issues.
2. The FDA’s review of tazemetostat found a lack of efficacy compared to standard therapies and the potential for secondary malignancies that short trial durations may not have fully described. But the FDA’s Oncologic Drugs Advisory Committee voted 11-0 with two abstentions to recommend approval of tazemetostat for the treatment of metastatic or inoperable locally advanced epithelioid sarcoma, due to the low response rate with currently approved treatments.
3. Deciphera filed an NDA for ripretinib for the treatment of gastrointestinal stromal tumors.
4. The FDA designated Orphazyme’s arimoclomol a Fast Track drug for the treatment of sporadic Inclusion Body Myositis.
5. PharmaMar submitted an NDA for lurbinectedin for the treatment of small cell lung cancer. 
6. The FDA designated Cascadian Therapeutics’ tucatinib a Breakthrough Therapy when given in combination with trastuzumab and capecitabine, for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer.
7. BMS filed a BLA for lisocabtagene maraleucel for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least two prior therapies.
8. MacroGenics filed a BLA for margetuximab for the treatment of patients with metastatic HER2-positive breast cancer in combination with chemotherapy.
9. Gilead submitted an NDA for filgotinib for the treatment of moderate-to-severe rheumatoid arthritis.
10. The FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee voted 12-0 to recommend approval of Horizon Therapeutics’ teprotumumab in December 2019 for the treatment of Thyroid Eye Disease.
11. The FDA lifted the clinical trial hold for Abeona Therapeutics’ EB-101 targeting recessive dystrophic epidermolysis bullosa
12. The FDA designated Dermira/Roche’s lebrikizumab a Fast Track treatment for moderate-to-severe atopic dermatitis.
13. The FDA Cardiovascular and Renal Drugs Advisory Committee voted 11-2 against recommending approval of Correvio’s vernakalant due to safety concerns over hypotension, arrhythmias, and conduction disturbance.
14. Biocryst submitted an NDA for BCX7353 in December 2019 with a hereditary angioedema indication.
15. Seattle Genetics plans to file an NDA and MAA for tucatinib in 1Q20.
16. The FDA rejected Lexicon Pharmaceuticals/Sanofi’s sotagliflozin a second time as a treatment for type 1 diabetes on 12/2/2019. Previously, 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 in January 2019. Some members of the committee expressed concern regarding the increased risk for diabetic ketoacidosis with the drug. The FDA rejected sotagliflozin as a treatment for type 1 diabetes on 3/22/2019. The EMA approved sotagliflozin in April 2019 for the treatment of Type 1 Diabetes. Sanofi ceased participation in the development of sotagliflozin in July 2019 after the results from 3 Phase III type 2 diabetes trials were announced. 
17. The FDA rejected RVT-802 on 12/5/19 due to manufacturing issues.
18. Immunomedics resubmitted the BLA for sacituzumab govitecan for the treatment of resistant metastatic triple-negative breast cancer.
19. The FDA has placed a partial clinical hold on four of Clementia’s palovarotene trials [(two fibrodysplasia ossificans progressiva (FOP) studies and two osteochondroma studies)] due to reports of early growth plate closure in patients with FOP in patients under the age of 14.