November 2022 decisions expected from the FDA

Your monthly synopsis of new drugs expected to hit the market 

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).  

 Drug pipeline for November 2022

11/17/2022: Tzield® (teplizumab)
The United States Food and Drug Administration (FDA) is reviewing Provention Bio’s Tzield for the delay of clinical type 1 diabetes in at-risk individuals at risk of developing the disease, defined as having two or more T1D-related autoantibodies. Tzield is seeking approval based on the Phase 2 clinical trial that demonstrated that a single 14-day infusion course of Tzield delayed the onset of clinical disease and insulin dependence in patients at risk for type 1 diabetes by approximately three years (median of 32.5 months), adding one year to previously reported results.1  Teplizumab disrupts patients’ autoimmune response and was found to reduce T1D diagnosis in at-risk patients by 59% versus placebo—as well as delay diagnosis by as long as three years in the Phase 2 At-Risk trial run by the NIH. Just 43% of participants treated with teplizumab were diagnosed with T1D, versus 73% of participants on placebo. On May 27, 2021 the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 10-7 in favor of the benefits, outweighing the risks of teplizumab to delay clinical type 1 diabetes mellitus.2 There are no drugs currently FDA approved for the delay of type 1 diabetes. 

 11/17/2022: sparsentan
Travere Therapeutics is seeking accelerated approval from the FDA for sparsentan for treatment of IgA nephropathy (IgAN). Sparsentan is a dual-acting receptor antagonist for endothelin (A type) and angiotensin II receptor (type 1). The new drug application (NDA) submission for sparsentan is supported by results from the ongoing pivotal Phase 3 PROTECT study which met its pre-specified interim primary efficacy endpoint measuring change in proteinuria compared to the active control irbesartan. After 36 weeks of treatment, patients receiving sparsentan achieved a mean reduction in proteinuria from baseline of 49.8%, compared to a mean reduction in proteinuria from baseline of 15.1% for irbesartan-treated patients.3 Sparsentan would be the second drug approved for IgAN but the first non-immunosuppressive agent. Calliditas’ Tarpeyo® (budesonide) was recently approved in December 2021. Other similar products include ACEi and ARBs. 

11/24/2022:poziotinib
The FDA is reviewing Spectrum Pharmaceuticals’ poziotinib for use in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations. The NDA is supported by data from cohort 2 of the Phase 2, ZENITH20 trial, which demonstrated that poziotinib, when given at a once-daily dose of 16mg, induced an objective response rate (ORR) of 27.8% in this population.4 The median duration of response (DOR) was 5.1 months, and the median progression-free survival (PFS) was 5.5 months. In September 2022, the FDA Oncologic Drugs Advisory Committee met to review poziotinib voting 9-4 that the current benefits of poziotinib did not outweigh its risks.5 Currently there are no FDA approved medications for this indication.  

11/24/2022: etranacogene dezaparvovec
The FDA is evaluating CSL Behring and UniQure’s etranacogene dezaparvovec for treatment of adults with hemophilia B. Etranacogene dezaparvovec is a gene therapy using an AAV5 vector to deliver the Padua gene variant of Factor IX (FIX-Padua). The FIX-Padua gene version was shown to result in FIX clotting activity that’s five to eight times greater than the activity normally associated with the FIX gene. Etranacogene dezaparvovec is given as a one-time IV infusion and is expected to increase FIX levels, helping to prevent and control bleeds. CSL Behring is seeking approval based on results from the pivotal HOPE-B trial, in 54 men with moderate to severe hemophilia B over five years. Patients with hemophilia B treated with etranacogene dezaparvovec demonstrated reduced adjusted annualized bleeding rate (ABR) by 64% and superiority to prophylaxis treatment at 18 months post-treatment compared to a six-month run in period.6 The yearly use of FIX replacement therapy, a standard hemophilia B treatment that provides the missing clotting factor, fell by 97%, and 98% of patients who received a full therapeutic dose stopped using prophylaxis, or preventive treatment. Current treatment includes life-long prophylactic infusions of FIX to temporarily replace or supplement low levels of the blood-clotting factor. 

11/26/2022: pegcetacoplan
Apellis Pharmaceuticals’ pegcetacoplan has been granted priority review from the FDA as an intravitreal formulation of the C3 complement inhibitor for treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). There are approximately one million patients in the U.S. with geographic atrophy (GA) secondary to AMD. Pegcetacoplan works by inhibiting a complement cascade centrally by binding to C3 and C3b to control excessive complement activation; this controls the irreversible lesion growth in geographic atrophy (GA), secondary to AMD. Pegcetacoplan is already approved as Empaveli subcutaneous injection for paroxysmal nocturnal hemoglobinuria. Pegcetacoplan is applying based on results from the Phase 3 DERBY (did not meet primary endpoint) and OAKS (met primary endpoint) studies at 12 and 18 months as well as the Phase 2 FILLY (met primary endpoint) study at 12 months. When results were pooled, treatment with both monthly and every-other-month pegcetacoplan resulted in a clinically meaningful reduction of GA lesion growth across a broad, heterogeneous population of more than 1,500 patients.7 Pegcetacoplan would be the first product approved for geographic atrophy due to AMD; approval may be limited to patients with GA lesions of specific size or location, and patients with no evidence of wet AMD. 

11/28/2022: mirvetuximab soravtansine
The FDA is evaluating ImmunoGen’s mirvetuximab soravtansine for treatment of patients with folate receptor alpha-high platinum-resistant ovarian cancer who have been previously treated with one to three prior systemic treatments. Mirvetuximab soravtansine is seeking approval based on the Phase 3, SORAYA trial, which demonstrated an investigator assessed ORR of 32.4% including a 4.8% complete response (CR) rate. The investigator-assessed median duration of response (DOR) was 6.9 months and the median time to response was 1.5 months. The disease control rate (DCR) was 51.4%, with a 71.4% tumor reduction rate.8 Similar products include AstraZeneca’s Lynparza® (olaparib), GlaxoSmithKline’s Zejula® (niraparib), Baxter’s Doxil® (doxorubicin), topotecan, paclitaxel and gemcitabine. 

11/30/2022: Omblastys® (131I-omburtamab)
Y-mAbs’ Omblastys is seeking an indication for treatment of pediatric patients with central nervous system and leptomeningeal metastasis from neuroblastoma. Omblastys demonstrated a twelve-month overall survival (“OS”) of 73.5%, with a median follow-up of 25 months. Further, the interim results showed an ORR of 31.3% in the patients with measurable disease after central review based on Response Assessment in Neuro-Oncology (RANO) criteria.9 The FDA is planning to hold an advisory committee meeting on Oct. 28, 2022 to discuss the application.10 Similar products include chemotherapy and surgery. 

11/2022: Rebyota® (RBX2660 fecal microbiota transplant)
The FDA is reviewing Ferring’s Rebyota for treatment of recurrent Clostridioides difficile (C diff) infection. Rebyota is a live fecal microbiota transplant. Ferring met its primary endpoint in Phase 3 trial demonstrating Rebyota had superior efficacy versus placebo (70.4% and 58.1%, respectively) at eight weeks post-treatment.11 The Vaccines and Related Biological Products Advisory Committee voted 13-4 in favor of the availability of adequate data supporting effectiveness and 12-4, with one abstention, in favor of the availability of adequate data supporting safety.12 Similar products include fecal microbiome transplant. 

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. 

1. https://www.fiercebiotech.com/biotech/provention-s-med-for-delaying-diabetes-granted-go-ahead-for-fda-resubmission
2. https://www.fda.gov/media/149542/download
3. https://www.globenewswire.com/en/news-release/2022/05/16/2443695/0/en/Travere-Therapeutics-Announces-FDA-Acceptance-and-Priority-Review-of-New-Drug-Application-for-Sparsentan-for-the-Treatment-of-IgA-Nephropathy.html 
4. https://www.onclive.com/view/fda-accepts-nda-for-poziotinib-in-her2-exon-20-mutated-nsclc 
5. https://www.businesswire.com/news/home/20220922005870/en/Spectrum-Pharmaceuticals-Provides-Update-on-Poziotinib-Following-FDA-Oncologic-Drugs-Advisory-Committee-Meeting 
6. https://hemophilianewstoday.com/amt-061/ 
7. https://investors.apellis.com/news-releases/news-release-details/apellis-announces-fda-acceptance-and-priority-review-new-drug-0 
8. https://www.onclive.com/view/mirvetuximab-soravtansine-displays-promising-efficacy-in-platinum-resistant-ovarian-cancerhttps://apnews.com/article/technology-health-business-covid-cancer-f1dffe6c80e601286fe62e1d65458b32 
9. https://www.globenewswire.com/news-release/2022/05/31/2453349/0/en/Y-mAbs-Announces-FDA-Acceptance-of-Biologics-License-Application-for-OMBLASTYS-omburtamab-for-the-Treatment-of-Neuroblastoma-for-Priority-Review.html 
10. https://www.ferring.com/ferring-and-rebiotix-present-landmark-phase-3-data-demonstrating-superior-efficacy-of-investigational-rbx2660-versus-placebo-to-reduce-recurrence-of-c-difficile-infection/ 
11. https://www.healio.com/news/gastroenterology/20220928/fda-panel-votes-in-favor-of-fecal-transplant-therapy-for-recurrent-c-difficile-infection