January 2022 decisions expected from the FDA

Your monthly synopsis of new drugs expecting FDA decisions in January 2022

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs likely to be approved by the U.S. Food and Drug Administration (FDA).

1/2022: somatrogon
The FDA is reviewing Pfizer and Opko Pharmaceuticals’ somatrogon as a once-weekly treatment of pediatric patients with growth hormone deficiency (GHD). Somatrogon’s application is based on a Phase 3 trial evaluating the safety and efficacy of somatrogon administered once weekly which met its primary endpoint of non-inferiority compared to once daily Genotropin^® (somatropin) for injection. The primary endpoint of the trial was height velocity at 12 months. Somatrogon demonstrated the least square mean was higher in the somatrogon group (10.12 cm/year) than in the Genotropin group (9.78 cm/year); the treatment difference between somatrogon and Genotropin groups in height velocity (cm/year) was 0.33.¹ Similar products include daily Novo Nordisk’s Norditropin^® (somatropin) and once daily Pfizer’s Genotropin^® (somatropin).

1/2022: Recorlev^TM (levoketoconazole)
The FDA is reviewing Strongbridge BioPharma’s Recorlev for chronic oral treatment of endogenous Cushing’s syndrome. The submission is supported by statistically significant results of the SONICS and LOGICS trials. These two Phase 3 trials evaluated the safety and efficacy of Recorlev used to treat adults with endogenous Cushing’s syndrome and found 30% of participants saw their cortisol levels normalize after six months of treatment with Recorlev compared to placebo, without requiring any dose increments during that period.² Similar products include Novartis Pharmaceuticals’ Signifor^® (pasireotide); and generic agents ketoconazole, metyrapone, etomidate and mitotane are commonly used off-label for Cushing’s disease.

1/2022: Leqvio^TM (inclisiran)
Novartis’ Leqvio is seeking approval from the FDA for treatment of primary hyperlipidemia. Leqvio is a small interfering RNA (siRNA) therapy dosed twice-yearly by a health care professional via subcutaneous injection. Leqvio demonstrated results from three Phase 3 trials ORION-9, ORION-10 and ORION-11, which assessed the safety, efficacy and tolerability of Leqvio in lowering LDL-Cholesterol levels. In the first study, patients with established cerebrovascular disease (CeVD) treated with Leqvio achieved an average 55.2% reduction in LDL-C from baseline compared with placebo. In the second study, patients with PVD treated with Leqvio achieved an average 48.9% reduction in LDL-C from baseline compared with placebo.³ Similar products include Regeneron and Sanofi’s Praluent^® (alirocumab) and Amgen’s Repatha^® (evolovumab).

1/5/2022: 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.⁴ 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.

1/8/2022: daridorexant
The FDA is reviewing Idorsia’s daridorexant for the treatment of insomnia. Daridorexant is an oral dual orexin receptor antagonist (DORA). In a Phase 3 trial, daridorexant showed statistically significant and clinically meaningful improvements in sleep during the night and, for the first time for an insomnia treatment, in daytime functioning, which were sustained over time compared to placebo.⁵ Patients significantly valued all seven outcomes but improving daytime functioning (relative attribute importance [RAI)] = 33.7%) and avoiding treatment withdrawal (RAI = 27.5%) were most important. If approved, Idorsia is planning to launch first half of 2022. Similar products include Eisai’s Dayvigo^® (lemborexant).

1/10/2022: Tezspire^TM (tezepelumab)
AstraZeneca and Amgen’s Tezspire^TM (tezepelumab) has been granted priority review by the FDA for treatment of patients with severe asthma across phenotypes. Tezspire is an antibody that blocks the epithelial cytokine thymic stromal lymphopoietin (TSLP).

The application was based on results from the Phase 3 trial NAVIGATOR in which Tezspire demonstrated superiority across every primary and key secondary endpoint compared to placebo. There were no clinically meaningful differences in safety results between the Tezspire and placebo groups in the NAVIGATOR trial.⁶ ICER’s analysis found Tezspire provides clinical benefit for patients with severe asthma, but with increased costs to the health care system. Tezspire would need to be priced between $9,000 and $12,000 annually to meet standard thresholds for cost-effectiveness, according to a review by the Institute for Clinical and Economic Review (ICER). But at an anticipated price of $28,000 per year, the therapy would exceed cost-effectiveness standards, and cost-effectiveness is only modestly improved when productivity and other effects are considered, according to the report.⁷ Treatment with Tezspire results in gains of 1.09 quality adjusted life year and 1.12 equal value life year. ICER uses this measure of cost effectiveness, as well as equal value life year (evLY), which measures any gains in length of life, regardless of the treatment’s ability to improve patients’ quality of life. From a health system perspective and using a placeholder net price of approximately $28,000 per year, ICER estimates a cost of $430,000 per QALY gained and $422,000 per evLY gained.⁷ Similar products include Sanofi and Regeneron’s Dupixent^® (dupilumab), Genentech’s Xolair^® (omalizumab), GSK’s Nucala^® (mepolizumab), AstraZeneca’s Fasenra^® (benralizumab) or inhaled corticosteroids.

1/2022: TPI-120 (pegfilgrastim biosimilar)
Amneal’s TPI-120 (pegfilgrastim biosimilar) is seeking approval from the FDA as a biosimilar version of Amgen’s long-acting granulocyte-colony stimulating factor (G-CSF) Neulasta^® (pegfilgrastim). Amneal intends to seek approval for the remainder of the indications from the reference product label as soon as possible, subject to patent and regulatory exclusivities, via the biosimilarity pathway pursuant to Section 351(k).⁸ Similar products include Amgen’s Neulasta^® (pegfilgrastim).

 1/27/2022: oteseconazole (VT-1161)
The FDA is reviewing Mycovia Pharmaceuticals’ oteseconazole for oral treatment of recurrent vulvovaginal candidiasis (RVVC). Oteseconazole is a fungal CYP51 inhibitor that blocks production of ergosterol. Clinical studies successfully met both their primary and key secondary endpoints by demonstrating oteseconazole protected more than 90% of participants from having a recurrence during the 48-week maintenance phase, compared to approximately 40% of those in the control group.⁹ Similar products include generic fluconazole.

 1/29/2022: faricimab
Genentech’s faricimab is being reviewed by the FDA for wet or neovascular age-related macular degeneration or diabetic macular edema.¹⁰ Faricimab is applying for approval based on two studies that measured average change in best-corrected visual acuity (BCVA) score (the best distance vision a person can achieve – including with correction such as glasses – when reading letters on an eye chart) from baseline through week 48. Both studies met their primary endpoint, with faricimab consistently shown to offer non-inferior visual acuity gains compared to aflibercept. In clinical trials TENAYA and LUCERNE, the average vision gains from baseline in the faricimab arms were +5.8 and +6.6 letters, respectively, compared to +5.1 and +6.6 letters in the aflibercept arms.¹¹ Similar products include Roche’s Lucentis^® (ranibizumab) or Regeneron’s Eyelea^® (aflibercept).

While the information in this newsletter is from sources we believe to be reliable, we do not warrant that the information in this document is free from error. Use it only as a guide. Statements regarding drugs or manufacturers are not intended as promotion; those statements should not be used to make assumptions about formulary status. Each trademarked drug name is the property of its respective owner.

References

1. https://www.pfizer.com/news/press-release/press-release-detail/ema-accepts-marketing-application-somatrogon-treat
2. https://cushingsdiseasenews.com/recorlev-levoketoconazole-cor-003/
3. https://www.pharmacytimes.com/view/analysis-of-inclisiran-show-effective-sustained-ldl-c-reduction-in-patients-with-atherosclerotic-cardiovascular-disease
4. https://www.empr.com/home/news/drugs-in-the-pipeline/new-drug-application-bxcl501-dexmedetomidine-sublingual-schizophrenia-bipolar/
5. https://www.globenewswire.com/news-release/2021/03/10/2190042/0/en/FDA-accepts-the-new-drug-application-for-review-of-Idorsia-s-daridorexant-for-the-treatment-of-adult-patients-with-insomnia.html
6. https://www.amgen.com/newsroom/press-releases/2021/07/tezepelumab-granted-priority-review-by-u-s–fda
7. https://www.managedhealthcareexecutive.com/view/icer-tezspire-not-likely-to-be-cost-effective-for-asthma
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299796/
9. https://www.businesswire.com/news/home/20210729005279/en/Mycovia-Pharmaceuticals-Announces-Presentation-of-Oteseconazole-VT-1161-Phase-3-Data-Demonstrating-Safety-and-Efficacy-for-Treatment-of-Recurrent-Vulvovaginal-Candidiasis-RVVC-at-the-2021-IDSOG-Annual-Meeting
10. https://www.modernretina.com/view/fda-accepts-genentech-s-bla-for-faricimab-for-treatment-of-wet-amd-and-dme
11. https://www.roche.com/media/releases/med-cor-2021-02-12.htm