Insights+: The US FDA New Drug Approvals in December 2019 and January 2020

• The US FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) have approved 48 new products so far in 2019
• However, there is a significant increase in multiple diseases while the new approvals are helping and advancing the changes to understand, diagnose and treat the diseases
• Our team at Pharmashots has compiled a list of 7 new drugs approved by the US FDA in December 2019 and January 2020

1.Sarepta Receives the US FDA’s Approval for VYONDYS 53 (golodirsen) Injection to Treat Duchenne Muscular Dystrophy (DMD) in Patients with Amenable to Skipping Exon 53

Published: Dec 12, 2019 | Tags: Amenable, Approval, DMD, Duchenne Muscular Dystrophy, Golodirsen Injection, Patients, Receives, Sarepta, Skipping, Exon 53, The US FDA, Treat, Vyondys 53

• Sarepta’s VYONDYS 53 is an antisense oligonucleotide derived using phosphorodiamidate morpholino oligomer (PMO) platform targeting DMD patients in patients with a confirmed mutation amenable to exon 53 skipping
• In Aug 2019, the company received a CRL for VYONDYS 53 from Drug Evaluation 1 following the New Drug Application (NDA) submission to and review by the Division of Neurology Products (the Review Division)
• VYONDYS 53 is approved under accelerated review based on increase in dystrophin production in skeletal muscle of patients amenable to exon 53 skipping and will be commercialized in the US and has also demonstrated safety and effectiveness

2. Astellas and Seattle Genetics’ PADCEV (enfortumab vedotin-ejfv) Receives the US FDA’s Approval for Locally Advanced or Metastatic Urothelial Cancer in Adults

Published: Dec 18, 2019 | Tags: Astellas, Seattle Genetics, PADCEV, enfortumab vedotin-ejfv, Receives, the US FDA; Approval, Locally Advanced, Metastatic, Urothelial Cancer, Adults  

• The PADCEV was evaluated in P-II EV-201 Trial to evaluate 125 patients locally advanced or metastatic urothelial cancer who received who received prior treatment with a PD-1 or PD-L1 inhibitor and a Pt-based CT
• The study resulted in ORR 44%, CR 12% leading no cancer detection at time of assessment, PR 32% meaning a decrease in tumor size or extent of cancer in the body, DoR 7.6 mos.
• PADCEV is a novel ADC directed against Nectin-4 a protein located on the surface of cells and highly expressed in bladder cancer and is currently evaluated in P-III EV-301Trial

3. Intra-Cellular’s CAPLYTA (lumateperone) Receives the US FDA’s Approval for the Treatment of Schizophrenia in Adults

Published: Dec 23, 2019 | Tags: Intra-Cellular, CAPLYTA, lumateperone, Receives, the US FDA, Approval, Treatment, Schizophrenia, Adults

• The approval is based on the study assessing CAPLYTA (42 mg) vs PBO while keeping Positive and Negative Syndrome Scale (PANSS) as 1EP
• The study resulted in somnolence/sedation (24% vs.10%) and dry mouth (6% vs. 2%)
•  CAPLYTA is a once-daily, oral therapy mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors

4. Eisai’s Dayvigo (lemborexant) Receives the US FDA’s Approval to Treat Insomnia in Adults

Published: Dec 23, 2019 | Tags: Eisai, Dayvigo, lemborexant, Receives, US, FDA, Approval, Treat, Insomnia, Adults

• The approval is based on two P-III studies (study 1 & 2) assessing Dayvigo (5mg/10mg, once nightly) vs PBO in patients aged ≥18yrs. & in female patients aged ≥55yrs. and male aged≥65yrs. for 6mos. & 1mos. who met DSM-5 criteria for insomnia disorder respectively
• The collaborative results indicated that Dayvigo demonstrated superiority sSOL, sSEF, sWASO, LPS, SEF and WASO, effect at the beginning of treatment were generally consistent with later timepoints
• The FDA has recommended Dayvigo to be classified as a controlled substance while recommendation has been submitted to the US DEA. Dayvigo is expected to be commercially available within 90 days following DEA scheduling

5. Blueprint Medicines’ Ayvakit (avapritinib) Receives FDA’s Approval to Treat Patients with Unresectable or Metastatic PDGFRA Exon 18 Mutant Gastrointestinal Stromal Tumor

Published: Jan 09, 2020 | Tags: Blueprint Medicines, Ayvakit, avapritinib, Receive, FDA, Approval, Treat, Patients, Unresectable, Metastatic, PDGFRA Exon 18, Mutant Gastrointestinal Stromal Tumor

• The US FDA approval is based on P-I NAVIGATOR trial assessing avapritinib (300mg or 400mg, qd) in 43 patients with unresectable or metastatic GIST harboring PDGFRA exon 18 mutations, including 38 patients with PDGFRA D842V mutations
• The study resulted in patients with PDGFRA exon 18 mutant GIST: ORR 84%, CR 7%, PR 77%. And in patients with PDGFRA D842V mutations: ORR 89%, CR 8%, PR 82%, mDOR was not reached
• Ayvakit (avapritinib) is a KIT and PDGFRA mutant kinases inhibitor and is novel candidate approved for type 1 inhibitor for GIST and has also received the US FDA’s BT Designation. The PDUFA date for fourth-line GIST indication is currently Feb 14, 2020

6. Horizon Therapeutics’ Tepezza (teprotumumab-trbw) Receives the US FDA’s Approval as the First Therapy for Thyroid Eye Disease

Published: Jan 22, 2019 | Tags: Approval, FDA, First Therapy, Horizon Therapeutics, Receives, Tepezza, Teprotumumab-Trbw, Thyroid Eye Disease, The US

• The US FDA’s approval of Tepezza is based on P-II study and P-III OPTIC study assessing Tepezza vs PBO in patients with thyroid eye disease. Tepezza was initially developed by River Vision and Roche, later Horizon acquired River Vision and will pay ~$105M as milestones in H1’2020   
• The P-III OPTIC study results: @24wks, improvement in proptosis (≥ 2 mm) (82.9% vs 9.5%) without deterioration in the fellow eye; change in at least one grade in diplopia (67.9% vs 28.6%). Pooled analysis demonstrated complete resolution of diplopia (53% vs 25%)
• Tepezza (q3w, for 8 infusions) is mAb targeting IGF-1R and has received the US FDA’s PR, ODD, BT designation with its anticipated PDUFA date as 08 Mar, 2020. The therapy is expected to be available in the US in the coming wks.

7. Epizyme’s Tazverik (tazemetostat) Receives the US FDA’s Accelerated Approval as the First Therapy for Epithelioid Sarcoma

Published: Nov 05, 2019 | Tags: Accelerated, Approval, Epizyme, FDA, First Therapy, Receives, Tazemetostat, Tazverik, The US  

• The approval is based on clinical P-II clinical study assessing Tazverik (800mg, bid) in 62 patients aged ≥16yrs. with metastatic or LA epithelioid sarcoma not eligible for complete resection. The study measures how many patients experienced a complete or partial shrinkage of their tumors during the treatment
• The P-II clinical study results: tumor response assessments were performed every 8 wks. ORR (15%); CR (1.6%); PR (13%); DoR of 6mos. or longer (67%)
• Tazverik is the first and only FDA-approved EZH2 inhibitor with its expected launch in the US within 10 working days. Additionally, Epizyme will conduct post-marketing activities including clinical pharmacology evaluations assessing the effect of the therapy on liver function and the effect of CYP3A inhibitors and inducers on Tazverik