April 2022 decisions expected from the FDA

4/5/2022: BXCL501 (dexmedetomidine orally dissolving film)
BioXcel Therapeutics’ BXCL501 is being reviewed by the FDA for acute treatment of agitation associated with schizophrenia and bipolar disorders I and II. BXCL501 is an orally dissolving thin film formulation of the selective alpha-2a receptor agonist. The NDA submission is supported by data from the Phase 3 clinical trials, SERENITY I and II, that evaluated the efficacy and safety of BXCL501. Results from both studies showed that BXCL501 met the primary end point achieving statistically significant and clinically meaningful reductions in the Positive and Negative Syndrome Scale-Excitatory Component (PEC) score at two hours compared to placebo.¹ Dexmedetomidine is currently available as a solution for intravenous infusion for use in clinical anesthesia and sedation in an intensive care setting. Similar products include generic olanzapine.

 4/14/2022: vutrisiran
The FDA is reviewing Alnylam Pharmaceuticals’ vutrisiran for treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. Vutrisiran is a second-generation formulation of Onpattro^® (patisiran) which is an RNA interference (RNAi) therapy that blocks production of wild-type and variant transthyretin protein. Vutrisiran’s primary advantage over Onpattro is its dosing regimen. Patients taking Onpattro must undergo an 80-minute infusion every three weeks. Vutrisiran, on the other hand, is a subcutaneous injection that is administered by a health care professional every three months. Vutrisiran is seeking approval based on HELIOS-A, a Phase 3 open-label study which evaluated the efficacy and safety of vutrisiran compared to the Onpattro IV infusion once every three weeks. The primary endpoint was the change from baseline in mNIS+7 score at nine months and vutrisiran was found to be non-inferior.² Similar products include Alnylam’s Onpattro^® (patisiran) and Akcea Therapeutics’ Tegsidri^® (inotersen).

4/2022: Lupifil-P (pegfilgrastim biosimilar)
Lupin’s Lupifil-P (pegfilgrastim biosimilar) is seeking approval from the FDA as a biosimilar version of Amgen’s Neulasta^® (pegfilgrastim). Neulasta is a long-acting granulocyte-colony stimulating factor (G-CSF). Lupifil-P is not seeking interchangeable status from the FDA. According to IQVIA pegfilgrastim has estimated annual sales of $3.66 billion in the U.S.³

4/28/2022: mavacamten
The FDA is reviewing Bristol-Myers Squibb’s mavacamten for oral treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten is an allosteric modulator of cardiac myosin that reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance. In clinical studies, mavacamten reduced biomarkers of cardiac wall stress, lessened excessive cardiac contractility and increased diastolic compliance. Mavacamten is seeking approval based on the Phase 3 EXPLORER-HCM trial that demonstrated statistically significant improvements according to the NYHA class reduction and/or improvement in peak oxygen consumption in 37% of patients taking mavacamten compared to 17% taking placebo.⁴ The Institute for Clinical and Economic Review (ICER) reviewed data from EXPLORER-HCM which led ICER to rate mavacamten in addition to first-line therapy as ‘promising but inconclusive’ compared to first-line therapy alone. They assigned the same rating to the evidence of mavacamten compared with disopyramide. ICER did not assign an evidence rating to the comparison of mavacamten versus septal reduction therapies. The cost-effectiveness analysis estimated the health benefit price benchmark for mavacamten to be $12,000-$15,000. Industry analysts have forecasted an annual price of $75,000.⁵ Similar products include beta and calcium channel blockers, or surgery.

 4/30/2022: surufatinib
Hutchmed’s surufatinib, an angio-immuno kinase inhibitor, is being reviewed by the FDA for treatment of pancreatic and extra-pancreatic neuroendocrine tumors (NETs). Surufatinib is seeking approval based on the Phase 3 SANET-p and SANET-ep clinical trials which demonstrated a median progression-free survival (PFS) of 10.9 months with surufatinib compared to a PFS of 3.7 months with placebo.⁶ The trial met the early stopping criteria at the interim analysis, the independent data monitoring committee recommended termination. Similar products include Pfizer’s Sutent^® (sunitinib malate).

4/30/2022: AXS-07 (MoSEIC™ meloxicam-rizatriptan)
Axsome Therapeutics’ AXS-07 (MoSEIC™ meloxicam-rizatriptan) for the acute treatment of migraine. MoSEIC is seeking approval via the 505(b)(2) pathway using Boehringer Ingelheim’s Mobic^® (meloxicam) and Merck’s Maxalt^® (rizatriptan) as reference products. Additionally, Axsome Therapeutics conducted two Phase 3 trials of AXS-07, the MOMENTUM and INTERCEPT trials, which demonstrated statistically significant elimination of migraine pain with AXS-07 compared to placebo and active controls.⁷ Similar products include generic meloxicam and generic rizatriptan.

4/30/2022: TV-46000 (risperidone extended-release injectable suspension)
Teva Pharmaceuticals and MedinCell’s TV-4600 is seeking approval from the FDA as a subcutaneous injection once monthly or every two months for treatment of schizophrenia. Teva applied via the 505(b)(2) pathway using Janssen’s Risperdal^® (risperidone) as its reference product.⁸ Existing risperidone injectable products on the market include Indivior’s Perseris^® (risperidone) and Janssen’s Risperdal Consta^® (risperidone).

4/2022: Tuoyi™ (toripalimab)
The FDA has granted priority review to Junshi Biosciences and Coherus’ Tuoyi for two separate indications: in combination with gemcitabine and cisplatin for first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma (NPC), as well as monotherapy for second-line or later treatment of recurrent or metastatic NPC patients with disease progression on or after platinum-containing chemotherapy. The application for the anti–PD-1 monoclonal antibody is supported by findings from both the phase 2 POLARIS-02 trial, which assessed Tuoyi in previously treated and recurrent or metastatic nasopharyngeal carcinoma, and the Phase 3 JUPITER-02 trial, examining gemcitabine and cisplatin with or without Tuoyi in recurrent of metastatic nasopharyngeal carcinoma. POLARIS-02 revealed durable clinical responses in those treated with Tuoyi with an overall response rate (ORR) of 20.5% and a median duration of response of 12.8 months. JUPITER-02 identified notable improvements in PFS achieving a median PFS of 11.7 months compared with eight months in patients treated with chemotherapy alone.⁹ Similar products include Merck’s Keytruda^® (pembrolizumab) and Bristol-Myers Squibb’s Opdivo^® (nivolumab).

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References

1. https://www.empr.com/home/news/drugs-in-the-pipeline/new-drug-application-bxcl501-dexmedetomidine-sublingual-schizophrenia-bipolar/
2. https://www.businesswire.com/news/home/20210624005230/en/Alnylam-Announces-U.S.-Food-and-Drug-Administration-Acceptance-of-New-Drug-Application-for-Investigational-Vutrisiran-for-the-Treatment-of-the-Polyneuropathy-of-Hereditary-ATTR-Amyloidosis
3. https://www.lupin.com/lupin-announces-u-s-fda-acceptance-for-pegfilgrastim-biosimilar-application/
4. https://www.managedhealthcareexecutive.com/view/mavacamten-first-in-class-therapy-may-soon-be-available-for-hypertrophic-cardiomyopathy
5. https://icer.org/wp-content/uploads/2021/04/ICER_HCM_Final_Evidence_Report_111621.pdf
6. https://www.onclive.com/view/fda-accepts-nda-for-surufatinib-for-advanced-neuroendocrine-tumors
7. https://www.globenewswire.com/news-release/2021/09/14/2296511/33090/en/Axsome-Therapeutics-Announces-FDA-Acceptance-of-New-Drug-Application-for-AXS-07-for-the-Acute-Treatment-of-Migraine.html
8. https://www.businesswire.com/news/home/20210831005934/en/Teva-and-MedinCell-Announce-FDA-Acceptance-of-New-Drug-Application-for-TV-46000mdc-IRM-as-a-Treatment-for-Patients-with-Schizophrenia
9. https://www.biospace.com/article/releases/eucure-biopharma-announces-encouraging-antitumor-activity-of-its-anti-cd40-antibody-in-pd-1-refractory-ocular-melanoma-when-combined-with-junshi-biosciences-toripalimab/