December 2020 decisions expected from the FDA

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage the new drugs that come on the market. 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).

12/1/2020: tanezumab
The FDA is reviewing Pfizer and Lilly’s tanezumab 2.5mg for treatment of chronic pain in patients with moderate to severe osteoarthritis (OA). Tanezumab is a monoclonal antibody nerve growth factor inhibitor that is administered subcutaneously once every eight weeks by a health care professional. In clinical trials, tanezumab 2.5mg reduced pain more than placebo; pain reduction was no different compared to NSAIDs. However, tanezumab increased the risk of rapidly progressive OA and total joint replacement compared to other treatment options and placebo.1 Similar products include generic NSAIDs or Pfizer’s Celebrex® (celecoxib).

12/1/2020: inclisiran
Novartis’ inclisiran is seeking approval from the FDA for the treatment of primary hyperlipidemia. Inclisiran is a first-in-class, small interfering RNA (siRNA) that is administered twice-yearly as a subcutaneous injection by a health care professional. A Phase 3 trial demonstrated that inclisiran, given to patients already taking their maximum-tolerated dose of statins, was able to lower LDL levels by an average of 54.1% when compared to placebo.3 Additionally, 88% of treated patients posted blood test results showing LDLs reduced by half at least once during the studies. Similar products include Regeneron’s Praluent® (alirocumab) and Amgen’s Repatha® (evolocumab).

12/3/2020: berotralstat (BCX7353)
The FDA is evaluating BioCryst’s berotralstat for prevention of hereditary angioedema (HAE) attacks. Berotralstat is a 150mg oral, once daily dose that targets plasma kallikrein protease. APeX-2, a Phase 3 trial, demonstrated berotralstat met its primary endpoint of HAE attack rate reduction compared with placebo (30% reduction at low dose of 110mg, 44% reduction at high dose of 150mg). Fifty percent of patients achieved at least a 70% reduction compared to baseline. Berotralstat reduced patients’ monthly use of standard of care (SoC) on-demand medicine by 53.6% compared to placebo, and reduced the number of HAE attacks requiring acute SoC treatment by 49.2% compared to placebo.4 Similar products include Shire’s Takhyzyro® (lanadelumab-flyo), CSL Behring US’s Haegarda® (C1 esterase inhibitor subcutaneous (human)), and Shire’s Cinryze® (C1 esterase inhibitor human).

12/3/2020: lumasiran
Alnylam’s lumasiran is being reviewed by the FDA for treatment of primary hyperoxaluria type 1 (PH1). PH1 is an ultra-rare disease, affecting only one to three individuals per million in the U.S. and Europe. Lumasiran targets glycolate oxidase to counter the overproduction of oxalate that leads to kidney damage with PH1. Lumasiran met the primary endpoint of ILLUMINATE-A study, achieving a significant reduction from baseline in 24 hour urinary oxalate excretion compared with placebo (65.4% reduction relative to baseline; mean treatment difference of 53.5% versus placebo.)5 Currently there are no FDA-approved medications for PH1.

12/19/2020: ABP 798 (rituximab biosimilar)
The FDA is reviewing Amgen and Allergan’s ABP 798 as a biosimilar of Genentech’s Rituxan® (rituximab). Rituxan is a CD20-directed cytolytic antibody that is approved for the treatment of adult patients alone or in combination with chemotherapy for non-Hodgkin’s lymphoma, in combination with fludarabine and cyclophosphamide for chronic lymphocytic leukemia, granulomatosis with polyangiitis and microscopic polyangiitis with glucocorticoids.6

12/18/2020: margetuximab
MacroGenics’ margetuximab is being reviewed by the FDA for use in combination with chemotherapy for treatment of metastatic HER2-positive breast cancer patients who have previously been treated with anti-HER2-targeted therapies. Approximately 15-20% of breast cancers cases are HER2-positve. Margetuximab has been engineered to increase its ability to mediate Fc domain-dependent activities, including enhanced tumor cell killing via antibody-dependent cell mediated cytotoxicity with potential to overcome resistance to Herceptin. Margetuximab is seeking approval based on SOPHIA, a Phase 3 trial, that compared margetuximab plus chemotherapy to trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer. Margetuximab demonstrated improved progression-free survival (PFS) compared with trastuzumab (5.8 versus 4.9 months) for a 24% risk reduction.7 Additionally, a subset of patients who were carriers of the CD16A 158F allele, demonstrated a risk reduction in PFS of 32%. Similar products include Genentech’s Herceptin® (trastuzumab) and its biosimilars.

12/20/2020: Evrenzo™ (roxadustat)
FibroGen Inc. and AstraZeneca’s Evrenzo is being reviewed by the FDA to treat anemia of chronic kidney disease (CKD) in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients. Evrenzo is a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin improving iron regulation and reducing hepcidin. Evrenzo demonstrated significantly higher increase in hemoglobin levels in DD patients compared with Epogen/Procrit, with mean change from baseline at 1.22g/dL and 0.99g/dL, respectively.8 Similar products include Amgen’s Aranesp® (darbepoetin alfa), Roche’s Mircera® (methoxy polyethylene glycol-epoetin beta) and Epogen/Procrit.

12/20/2020: Relumina™ (relugolix)
The FDA is reviewing Myovant’s Relumina for treatment of men with advanced prostate cancer. Relumina is an oral once-daily LHRH receptor antagonist. Relumina is seeking approval based on Phase 3 HERO trial, where the primary endpoint was testosterone suppression (</=50ng/dl). Relumina met its primary endpoint with 96.7% of the patients treated with relugolix achieved sustained testosterone suppression to castrate level.⁹ Similar products Ferring Pharmaceutical’s Firmagon^® (degarelix for injection), and AbbVie’s Lupron^® (leuprolide acetate).

12/26/2020: vibegron
The FDA is reviewing Sumitomo Pharmaceuticals Co. Ltd.’s vibegron for treatment of overactive bladder (OAB), including patients with symptoms of urge urinary incontinence, urgency, and urinary frequency. Vibegron is a beta-3 agonist that is being marketed as a faster acting, more tolerable option than its competitors. Vibegron is seeking approval based on a Phase 3 clinical trial that evaluated its safety and efficacy with the primary endpoint of the change from baseline in the average number of micturition’s and urgency episodes per 24 hours at week 12.¹⁰ Vibegron reduced daily urge urinary incontinence episodes by 0.6 and micturition by 0.5 compared to placebo. Similar products include Astellas Pharma’s Myrbetriq^® (mirabegron).

12/26/2020: ansofaxine (LY-03005)
Luye Pharma Group, Ltd is seeking approval by the FDA for ansofaxine for the treatment of major depression disorder. Ansofaxine is a serotonin-norepinephrine-dopamine triple reuptake inhibitor (SNDRI) in extended-release tablet form. Compared to traditional antidepressants, ansofaxine is expected to help preserve patients’ sexual function, have a better safety profile and produce a more rapid onset with higher efficacy.¹¹ Similar products include selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI).

12/27/2020: MYL-14020 (Avastin biosimilar)
Mylan NV and Biocon Ltd. are applying for approval for MYL-14020, an Avastin biosimilar for the first-line treatment of patients with stage IV non-squamous non-small cell lung cancer. Mylan NV is seeking approval based on Phase 3 efficacy and safety data versus the reference product, Roche’s Avastin.¹² MYL-14020 had an objective response rate (ORR) within the predefined equivalence margins when compared to Avastin.

12/29/2020: Ontinua™ ER (arbaclofen, extended release)
Osmotica is seeking approval from the FDA for Ontinua ER as an oral treatment for spasticity associated with multiple sclerosis. Ontinua ER is a twice daily, gamma-amino butyric acid-B (GABA-B) agonist. Ontinua ER allows for a slower release over a longer period of time, potentially reducing dosing frequency and undesirable side effects compared to other approved multiple sclerosis spasticity medications. Phase 3 clinical trials demonstrated safety and effectiveness of Ontinua ER while lowering patients TNmAS-MAL scores, (a measurement of muscle spasticity) when compared to placebo.¹³ Similar products include generic baclofen.

12/30/2020: Furoscix™ (subcutaneous furosemide, sc2Wear furosemide infusor-drug/device combination)
The FDA is evaluating scPharmaceuticals’ Furoscix for diuresis in patients with worsening heart failure. Furoscix is a wearable formulation of furosemide delivered subcutaneously to allow patients to diuresis at home instead of an IV infusion in the hospital. It is a self-administered pre-programmed drug delivery system. Furoscix is applying for approval via the 505(b)(2) pathway using Pfizer’s Lasix^® (furosemide) as its reference drug.¹⁴ Similar products include IV furosemide.

12/30/2020: tirbanibulin (ALM14789)
Athenex and Almirall’s tirbanibulin ointment is seeking approval from the FDA for the treatment of actinic keratosis (AK). Tirbanibulin is a Src kinase/pretublin dual inhibitor. Tirbanibulin based its application on two Phase 3 studies that met the primary endpoint of 100% clearance of actinic keratosis lesions at day 57 within the face or scalp. Complete clearance was observed in 44% of tirbanibulin patients in the first study compared to 5% of patients treated with vehicle, and 54% of tirbanibulin patients in the second study compared to 13% of vehicle treated patients. Tirbanibulin was found to be statistically significant in both groups.¹⁵ Similar products include topical fluorouracil, Perrigo’s Aldara^® (imiquimod), Leo Pharma’s Picato^® (ingenol mebutate) gel, and diclofenac.

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.

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References

1. https://investor.lilly.com/news-releases/news-release-details/us-fda-accepts-regulatory-submission-tanezumab-potential-first
2. https://www.healio.com/news/rheumatology/20201006/higher-doses-of-tanezumab-linked-to-abnormal-peripheral-sensation-vs-nsaids-in-oa
3. https://www.fiercebiotech.com/biotech/esc-novartis-twice-yearly-inclisiran-cuts-bad-cholesterol-by-at-least-30-nearly-all
4. https://www.biospace.com/article/releases/berotralstat-bcx7353-significantly-reduced-use-of-acute-on-demand-medicine-in-hae-patients-in-apex-2/
5. https://www.fiercebiotech.com/biotech/alnylam-phase-3-links-lumasiran-to-clinically-significant-improvement-infants
6. https://www.amgen.com/media/news-releases/2019/12/amgen-and-allergan-submit-biologics-license-application-for-abp-798-biosimilar-candidate-to-rituxan-rituximab-to-us-food-and-drug-administration/
7. https://www.macrogenics.com/margetuximab-anti-her2/
8. https://www.fiercepharma.com/special-report/4-roxadustat
9. https://www.onclive.com/view/fda-grants-priority-review-to-relugolix-for-advanced-prostate-cancer
10. https://www.fiercebiotech.com/biotech/as-urovant-preps-to-launch-myrbetriq-rival-it-s-all-systems-go-r-d
11. https://en.prnasia.com/releases/global/nda-filing-for-luye-pharma-s-antidepressant-drug-ly03005-accepted-by-the-u-s-fda-274200.shtml
12. https://www.centerforbiosimilars.com/view/positive-equivalency-data-for-a-trio-of-biosimilars-is-reported
13. https://multiplesclerosisnewstoday.com/news-posts/2020/07/22/fda-agrees-to-review-arbaclofen-er-potential-ms-spasticity-treatment/#:~:text=29%2C%202020.,disorders%20involving%20the%20spinal%20cord.
14. https://www.scpharmaceuticals.com/what-we-do/
15. https://www.globenewswire.com/news-release/2019/10/28/1936003/0/en/Athenex-Announces-Progress-Update-from-Partner-Almirall-on-Tirbanibulin-Ointment.html