July 2021 decisions expected from the FDA

Your snapshot of new drugs expecting FDA decisions in July 2021

June 11, 2021
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 July 2021
7/1/2021: Lantidra® (donislecel)

The FDA is reviewing CellTrans’ Lantidra, a novel cellular therapy for use in an uncommon, severe form of diabetes referred to as brittle type 1 diabetes (T1D) whose symptoms are not well controlled despite intensive insulin therapy. CellTrans estimates that fewer than 80,000 American adults have brittle type 1 diabetes. Lantidra consists of purified allogeneic pancreatic islets of Langerhans derived from single cadaveric donors, cultured and then infused into the portal vein of the liver. Lantidra is seeking approval based on two open-label studies that enrolled a total of 30 subjects who received 56 combined transplants. The clinical trial’s primary endpoint was a HbA1c level of 6.5% or less or an absence of severe hypoglycemic events at one year after the last transplant, which Lantidra met. However, both studies began prior to the FDA’s September 2009 guidance on development considerations; therefore, the FDA believes that the “substantial missing data and inclusion of a significant proportion of subjects who, at baseline, had already met or nearly met the primary endpoint makes this efficacy analysis difficult to interpret.”1 Results showed 63% of patients in the pooled analysis achieved treatment success as defined by the study’s primary endpoint. Of the 30 subjects across the two trials, 25 (83.3%) became insulin independent for any duration. Among these 25 subjects, four were insulin independent for less than one year, 11 for one to five years, and 10 subjects for more than five years. The FDA found no evidence that the duration of insulin independence could be predicted by baseline factors, including severe hypoglycemic events, or the total number of transplants received.1 Additionally, Lantidra has severe risks associated with the treatment including life-threatening procedural complications and complications from immunosuppression, such as serious infections and cancer. Two patients died, one as a result of fulminant sepsis at 20 months post-transplant, and the other as a result of severe dementia, 9 years post-transplant. On April 15, 2021 the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee evaluated Lantidra’s ability to demonstrate a favorable risk-benefit profile with patients with difficult to control type 1 diabetes. Committee members voted 12 yes, 4 no, and 1 abstention.2 Panelists on both sides said the therapy should be limited only to a very small group of patients, and that population may shrink further as devices for regulating insulin continue to improve. The panelists who voted “no” on the benefit-risk question expressed concern about potential risk associated with long-term immunosuppression and the size of the real-world population who had potential to benefit from the therapy. They raised concerns about the design and patient selection for CellTrans’ two studies, including the lack of a control group.

They also questioned how relevant the clinical trial data are to current-day patients since the studies were begun before the availability of glucose monitoring and insulin dosing systems, now considered standard of care. For patients in need, current therapy options include a whole-pancreas transplantation with or without concurrent kidney transplant or daily insulin injections.

7/2/2021: teplizumab

Provention Bio’s teplizumab is being reviewed by the FDA to delay or prevent clinical type 1 diabetes (T1D) in individuals at risk of developing the disease, defined as having two or more T1D-related autoantibodies. Teplizumab is seeking approval based on Phase 3 clinical trial that demonstrated that a single 14-day infusion course of teplizumab 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.3 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.4 Similar products include daily insulin injections.

7/7/2021: avacopan

The FDA is reviewing Chemocentryx’s avacopan for treatment of patients with ANCA-associated vasculitis. Avacopan is an orally administered selective complement 5a receptor inhibitor. Avacopan is seeking approval based on Phase 3 ADVOCATE trial that compared avacopan to prednisone. Results demonstrated that at week 26, 72% of patients receiving avacopan were in remission, compared to 70% of prednisone patients which was noninferior. At week 52, 66% of avacopan patients were in remission compared to 55% of prednisone patients which was superior.5 In May, the FDA Advisory Committee evaluated avacopan and voted a 9–9 split on whether the efficacy data supported approval of avacopan and 10–8 that the therapy’s safety profile adequately supported approval. In a third question, the committee voted 10–8 in favor of the benefit-risk profile supporting the approval at the proposed dose of 30mg twice daily. According to a briefing document released by the agency, “complexities of the study design… raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of autoantibody-associated vasculitis.”6

7/9/2021: finerenone

The FDA has granted priority review to Bayer Pharmaceuticals’ finerenone as a non-steroidal, selective mineralocorticoid receptor antagonist (MRA) for treatment of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Finerenone is seeking approval based on Phase 3 clinical trial FIGARO-DKD, that demonstrated finerenone significantly reduced the risk of the composite primary endpoint of cardiovascular death and non-fatal cardiovascular events compared to placebo when added to standard of care. FIGARO-DKD is the second positive Phase 3 study within the finerenone study program in CKD and T2D to meet its primary endpoint.7 Current guideline directed therapies are angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) or diuretics in diabetic nephropathy which are inexpensive first-line options.

7/20/2021: Bylvay® (odevixibat)

The FDA is reviewing Albireo’s Bylvay (odevixibat) for the treatment of pruritus in patients with progressive familial intrahepatic cholestasis (PFIC). PFIC is a rare disorder affecting young children that if untreated could progress into life-threatening liver disease. Bylvay is once-daily, non-systemic ileal bile acid transport inhibitor (IBATi). Bylvay is seeking approval based on two Phase 3 clinical trials, the first one evaluating the efficacy and tolerability of Bylvay compared to placebo and the second, a long-term, open-label extension study. In the first trial, PEDFIC 1, Bylvay met both the pruritus and serum bile acid primary endpoints while demonstrating it was well tolerated with very low incidence of diarrhea/frequent bowel movements (9.5% of Bylvay treated patients compared to 5.0% of placebo patients).8 The second trial PEDFIC 2, confirmed Bylvay sustained reductions in serum bile acid. Currently, PFIC is treated with surgical options because there are no similar products that are FDA approved.

7/25/2021: sulopenem etzadroxil and probenecid

Iterum Therapeutics’ sulopenem etzadroxil and probenecid is being reviewed by the FDA for treatment of uncomplicated urinary tract infections (uUTIs) in patients with a quinolone non-susceptible pathogen. Sulopenem etzadroxil and probenecid is an oral bilayer tablet formulation of the penem antibiotic. Sulopenem etzadroxil and probenecid’s application is based on the Phase 3 clinical trial, SURE-1 which demonstrated efficacy, tolerability and safety of oral sulopenem etzadroxil and probenecid, compared to oral ciprofloxacin. In patients with pathogens resistant to quinolones, sulopenem etzadroxil and probenecid was superior to ciprofloxacin; however, sulopenem etzadroxil and probenecid did not prove to be non-inferior to ciprofloxacin in organisms susceptible to quinolones.9 Similar products include generic ciprofloxacin.

7/25/2021: retifanlimab

The FDA is reviewing Incyte Corporation’s retifanlimab for treatment of adults with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on, or are intolerant of, platinum-based chemotherapy. Retifanlimab is an intravenous PD-1 inhibitor immuno-oncologic. Retifanlimab is seeking approval based on the Phase 2, POD1UM-202 trial which evaluated retifanlimab in previously treated patients with locally advanced or metastatic SCAC who have further progressed or cannot tolerate standard platinum-based chemotherapy. Retifanlimab had an objective response rate (ORR) of 14% for retifanlimab monotherapy and a median duration of 9.5 months.10 Similar products include Merck’s Keytruda® (pembrolizumab) and Bristol-Myers Squibb’s Opdivo® (nivolumab).

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://medicaldialogues.in/diabetes-endocrinology/news/fda-ppanel-agrees-on-islet-cell-treatment-for-type-1-diabetes-76667#:~:text=On%20April%2015%2C%20the%20members,of%20donislecel%20(Lantidra)%20approval.

2. https://www.fda.gov/media/147529/download

3. https://www.prnewswire.com/news-releases/provention-bio-provides-regulatory-update-on-biologics-license-application-for-teplizumab-for-the-delay-or-prevention-of-clinical-type-1-diabetes-in-at-risk-individuals-301265454.html

4. https://www.biospace.com/article/fda-advisory-committee-gives-narrow-nod-of-approval-for-provention-bio-s-teplizumab/

5. https://www.globenewswire.com/news-release/2020/09/17/2095212/0/en/ChemoCentryx-Announces-FDA-Acceptance-of-the-Avacopan-New-Drug-Application-NDA-for-the-Treatment-of-ANCA-Associated-Vasculitis.html

6. https://ancavasculitisnews.com/2021/05/10/fda-advisory-committee-narrowly-supports-approval-of-avacopan/

7. https://www.businesswire.com/news/home/20210510005034/en/Bayer%E2%80%99s-Finerenone-Meets-Primary-Endpoint-in-Phase-III-FIGARO-DKD-Cardiovascular-Outcomes-Study-in-Patients-With-Chronic-Kidney-Disease-and-Type-2-Diabetes

8. https://www.biospace.com/article/releases/albireo-receives-positive-chmp-opinion-for-bylvay-odevixibat-for-treatment-of-progressive-familial-intrahepatic-cholestasis-pfic-/

9. https://www.globenewswire.com/news-release/2020/12/07/2140496/0/en/Iterum-Therapeutics-Announces-Filing-of-US-Patent-Application-Based-on-Favorable-Written-Opinion-of-the-International-Search-Authority.html

10. https://investor.incyte.com/press-releases/press-releases/2021/Incyte-Announces-Acceptance-and-Priority-Review-of-BLA-for-Retifanlimab-as-a-Potential-Treatment-for-Patients-with-Squamous-Cell-Carcinoma-of-the-Anal-Canal-SCAC/default.aspx

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