August 2023 decisions expected from the FDA

Drug Pipeline August 2023

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).

8/2/2023: remestemcel-L
The FDA is reviewing Mesoblast’s remestemcel-L (formerly Ryoncil) for treatment of children with steroid-refractory acute graft-versus-host disease (SRaGVHD). Remestemcel-L is an allogeneic cell therapy comprising culture-expanded mesenchymal stromal cells derived from bone marrow of an unrelated donor and administered in a series of intravenous infusions. Three clinical trials of remestemcel-L demonstrated that, in an aggregated dataset, 66% (204 of the 309) of patients achieved an overall response at day 28 following a four-week course.¹ Results were consistent across all grades of disease, including the most severe. Currently there are no FDA-approved treatments for those 12 and under with SR-aGVHD.

8/4/2023: PDP-716 (brimonidine tartrate 0.35%)
The FDA is reviewing Visiox and Sun Pharma Advanced Research Company’s PDP-716 (brimonidine tartrate 0.35%) which is a once-daily ophthalmic suspension formulation of the alpha-2 agonist for treatment of glaucoma. PDP-716 is seeking approval via the 505(b)(2) pathway using Allergan’s AlphaganP^® (0.1%) as its reference product.² PDP-716 may provide an additional brimonidine option for patients unable or unwilling to use an eye drop three times daily, however, adverse effects may be higher with the once-daily formulation. Similar products include generic brimonidine tartrate 0.2%.

8/5/2023: zuranolone
Sage Therapeutics/Biogen’s zuranolone has been granted priority review by the FDA for adults with major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is a neuroactive steroid GABA-A receptor positive allosteric modulator intended for a rapid-acting, 14-day oral short course of treatment. Zuranolone is being evaluated based on the clinical programs LANDSCAPE and NEST which include multiple studies of zuranolone in several thousand people with a variety of dosing, clinical endpoints, and treatment paradigms. Overall, zuranolone met its primary endpoint compared to placebo.³ Similar products include Sage Therapeutics Zulresso^® (brexanolone), and Janssen’s Spravato^® (esketamine).

8/9/2023: talquetamab
The FDA is reviewing Johnson & Johnson (Janssen)’s talquetamab for treatment of relapsed or refractory multiple myeloma (RRMM). Talquetamab is an off-the-shelf bispecific T-cell engager antibody targeting G protein-coupled receptor family C group 5 member D (GPRC5D) and CD3. Talquetamab is seeking approval based on results from the Phase 1/2, MonumenTAL-1 trial which demonstrated an overall response rate (ORR) of 74.1 percent and 73.1 percent with a median duration of response (DOR) of nine months or longer.⁴ Similar products include Janssen Biotech’s Carvykti^® (ciltacatagene autoleucel) and Bristol Myers Squibb’s Abecma^® (idecabtagene vicleucel).

8/9/2023: avasopasem manganese
The FDA is reviewing Galera Therapeutics’ avasopasem manganese, a selective dismutase mimetic to reduce radiotherapy (RT)-induced severe oral mucositis (SOM) in patients with head and neck cancer (HNC) undergoing standard-of-care treatment.

Avasopasem manganese is seeking approval based on the GT-201 clinical trial that met its primary endpoint by demonstrating a 92% reduction in median number of days of SOM compared to placebo.⁵ There are currently no FDA-approved drugs to reduce SOM for these patients.

8/14/2023: Hepzato Kit™ (melphalan chemosaturation system)
The FDA is reviewing Delcath Systems’ Hepzato Kit, formerly Melblez Kit as a drug/device combination that delivers high-dose alkylating chemotherapy by percutaneous hepatic perfusion for treatment of unresectable hepatic-dominant metastatic ocular melanoma (mOM). Hepzato Kit is seeking approval via the 505(b)(2) pathway using Apotex’s Alkeran^® (melphalan) as its reference product.⁶ Similar products include melphalan.

 8/16/2023: Sohonos™ (palovarotene)
The FDA has granted priority review to Ipsen/Clementia’s palovarotene for prevention of heterotopic ossification (new bone formation) in patients with fibrodysplasia ossificans progressiva (FOP). FOP has an estimated prevalence of 1.36 per million individuals; however, the number of confirmed cases varies by country.⁷ Palovarotene is an oral selective retinoic-acid receptor gamma (RARγ) agonist. The FDA Advisory committee voted 10-4 in favor of effectiveness of Sohonos and 11-3 in favor benefits outweigh the risks. Currently there are no FDA-approved products for this indication.

8/19/2023: Zimura™ (avacincaptad pegol (ACP))
The FDA is reviewing Iveric Bio’s Zimura, a complement C5 protein inhibitor for treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Zimura is being evaluated based on the Phase2/3 GATHER1 and Phase 3 GATHER2, trials that measured the efficacy and safety of monthly 2mg intravitreal administration of ACP in patients with GA secondary to AMD. The primary efficacy endpoints in both pivotal studies were based on GA area measured by fundus autofluorescence (FAF) at three time points: Baseline, Month 6, and Month 12. GATHER1 demonstrated at 12 months, the 2mg and 4mg doses of Zimura resulted in 27% and 28% less growth in geographic atrophy (GA), respectively, compared to sham treatments. GATHER2 demonstrated that the treatment group experienced a 14.3% reduction in GA lesion size vs. sham treatment at 12 months.⁸ Similar products include Apellis Pharmaceuticals’ Syfovre^® (pegcetacoplan injection).

8/20/2023: pozelimab
Regeneron’s pozelimab is seeking approval from the FDA for CHAPLE disease. CHAPLE disease is a life-threatening hereditary immune disease caused by an overactivation of the complement system. The BLA submitted to the FDA is supported by the data obtained from an open-label Phase 2/3 trial, designed to evaluate the efficacy and safety of pozelimab in ten patients aged one year or above that is currently underway-results not yet available.⁹ Currently there are no FDA approved treatments however Alexion’s Soliris^® (eculizumab) is used off label.

8/22/2023: elranatamab
The FDA has granted priority review of Pfizer’s elranatamab (PF-06863135) an ‘Off the shelf’ humanized bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3 formulated for subcutaneous delivery for treatment of relapsed or refractory multiple myeloma (RRMM). Elranatamab is being investigated as a fixed dose subcutaneous administration. Elranatamab is seeking approval based on the Phase 2 MagnetisMM-3 an open-label, multicenter, nonrandomized trial of elranatamab. MagnetisMM-3 enrolled two independent cohorts of participants: one with and one without prior treatment with a BCMA-directed antibody-drug conjugate (ADC) or CAR-T therapy. Elranatamab demonstrated an ORR of 60.6%. At data cut-off, 89.5% of objective responders were ongoing without confirmed progression or death.¹⁰ Similar products include Janssen Biotech’s Carvykti^® (ciltacatagene autoleucel), Bristol Myers Squibb’s Abecma^® (idecabtagene vicleucel), Janssen’s Tecvayli^® (teclistamab-cqyv) and Karyopharm Therapeutics’ Xpovio^® (selinexor).

Contact your Prime representative for more information or with any questions you have about drugs in the pipeline.

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.cancernetwork.com/view/fda-accepts-remestemcel-l-bla-resubmission-for-pediatric-acute-gvhd
2. https://www.glaucomaphysician.net/issues/2023/march-2023/visiox-submits-nda-for-first-once-daily-brimonidin
3. https://investors.biogen.com/news-releases/news-release-details/biogen-and-sage-therapeutics-announce-fda-accepts-filing-new
4. https://www.jnj.com/janssen-presents-new-data-for-talquetamab-a-first-in-class-gprc5dxcd3-bispecific-antibody-suggesting-durable-responses-in-patients-with-heavily-pretreated-multiple-myeloma
5. https://www.galeratx.com/our-pipeline/avasopasem/
6. https://www.prnewswire.com/news-releases/delcath-systems-inc-announces-fda-acceptance-of-new-drug-application-resubmission-of-hepzato-kit-with-a-pdufa-date-of-august-14-2023-301782008.html
7. https://www.ipsen.com/press-releases/ipsen-receives-new-fda-pdufa-date-for-investigational-palovarotene-for-the-treatment-of-people-with-fop/
8. https://investors.ivericbio.com/news-releases/news-release-details/iveric-bio-present-top-line-results-avacincaptad-pegol-phase-3
9. https://www.pharmaceutical-technology.com/news/fda-regeneron-pozelimab-bla/
10. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elranatamab-receives-fda-and-ema-filing-acceptance