August 2022 decisions expected from the FDA

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 August 2022

8/1/2022: SB5 (adalimumab-bwwd 100mg/mL biosimilar)
The FDA is reviewing Samsung Bioepis and Organon’s adalimumab-bwwd as a citrate-free, high-concentration (100mg/mL) formulation of the biosimilar version of AbbVie’s Humira^® (adalimumab). Samsung Bioepis and Organon already have a low-concentration (50mg/mL) formulation approved as Hadlima^®.¹ If approved it is expected to launch in the U.S. on or after July 1, 2023.

8/2022: TX05 (trastuzumab biosimilar)
Tanvex’s TX05 is being reviewed by the FDA as a biosimilar to Roche’s Herceptin^® (trastuzumab). TX05 has demonstrated equivalence in patients with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer. The overall response rate (ORR) was highly similar between the TX05 (84.3%) and trastuzumab (85.0%) groups, and findings for patients with complete response, partial response, and stable disease were also highly similar among cohorts.² Similar products include Roche’s Herceptin^® (trastuzumab), and the five additional biosimilars that are already approved: Ogivri^® Herzuma^® Ontruzant^® Trazimera^® Kanjinti^®.

 8/19/2022: betibeglogene autotemcel (beti-cel)
Bluebird bio’s betibeglogene autotemcel is seeking approval from the FDA for treatment of transfusion-dependent beta-thalassemia (TDT). This is a gene therapy that provides a potentially curative option for patients with TDT. TDT, the most severe form of this disease, is managed through lifelong regular blood transfusions and iron chelation therapy to avert the consequences of iron overload. There are approximately  1300 people in the US living with TDT. The systematic review yielded five studies of betibeglogene autotemcel: two Phase 1/2 trials, two Phase 3 trials, and one long-term follow-up cohort study of trial participants. Each of the four trials were open-label single-arm designs. Transfusion independence in the Phase 3 trials was achieved in 89% of the patients who received betibeglogene autotemcel. Transfusion independence among patients treated in Phase 1/2 and Phase 3 trials was sustained over a median length of follow-up of 42 months (range 23-87 months).⁴ The Institute for Clinical and Economic Review (ICER) graded betibeglogene autotemcel as a substantial B+. Because of the questions about risks and the durability of the clinical benefit, ICER stated that the evidence demonstrates that betibeglogene autotemcel is superior overall to the current standard of care, but the magnitude of that overall net health benefit is less certain.⁴ The manufacturer suggests that betibeglogene autotemcel pricing will be $2.1 million for the one-time treatment.⁴ The FDA Advisory Committee panel voted 13-0 that the benefits of betibeglogene autotemcel outweigh the risks for the treatment of subjects with transfusion-dependent beta-thalassemia.⁵ Similar products include allogeneic hematopoietic stem cell transplantation.

8/28/2022: Defencath^® (taurolidine, heparin and citrate)
The FDA is reviewing CorMedix Inc.’s Defencath as prevention of catheter-related bloodstream infections (CRBSIs) in patients with end-stage renal disease who are receiving hemodialysis via a central venous catheter. Taurolidine is a non-antibiotic agent with broad-spectrum antimicrobial activity, which has been used as a lock solution to prevent catheter-related bloodstream infections in some settings. The primary objective of the Phase 3 trial, LOCK-IT-100, was to demonstrate the efficacy and safety of Defencath as a catheter lock solution (CLS) for prevention of catheter-related bloodstream infection (CRBSI) in subjects receiving hemodialysis (HD) for the treatment of end stage renal disease (ESRD) when compared with heparin. Defencath demonstrated a 71% reduction in catheter-related bloodstream infections relative to the heparin control arm.⁷ Currently, there are no FDA-approved pharmacological agents for prevention of CRBSIs, however heparin sodium is used off-label.

8/29/2022: Miglustat™ (with cipaglucosidase alfa)
The FDA is reviewing Amicus Therapeutics’ miglustat in combination with cipaglucosidase alfa to treat patients with Pompe disease. Pompe is a very rare disease, with an estimated incidence of 1 in 20,000 to 100,000 births and a worldwide prevalence of 5,000 to 10,000 individuals. The two-component therapy for Pompe disease is comprised of the intravenous enzyme-replacement therapy (ERT) cipaglucosidase alfa co-administered with the oral molecular chaperone miglustat cipaglucosidase alfa. An enhanced version of the standard of care, Sanofi’s Lumizyme^® (alglucosidase alfa), contains modifications in the protein backbone and in the surface glycosylation pattern to reduce immunogenicity and to enhance targeting to key affected muscles. Miglustat is applying for approval based on the Phase 3 PROPEL study of its combination therapy, AT-GAA, for the treatment of late onset Pompe disease (LOPD). Miglustat did not meet the primary endpoint of the study of the six-minute walk test (6MWT) when comparing the group given AT-GAA with the ERT-naive group receiving the current standard of care, alglucosidase alfa.⁸

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://www.organon.com/news/fda-accepts-samsung-bioepis-and-organons-sbla-for-their-citrate-free-high-concentration-humira-adalimumabbiosimilar-candidate/
2. https://www.centerforbiosimilars.com/view/tanvex-presents-positive-findings-for-trastuzumab-candidate-at-esmo
3. https://www.centerforbiosimilars.com/view/tanvex-presents-positive-findings-for-trastuzumab-candidate-at-esmo
4. https://investor.bluebirdbio.com/news-releases/news-release-details/long-term-data-bluebird-bios-betibeglogene-autotemcel-beti-cel
5. https://icer.org/wp-content/uploads/2021/11/ICER_Beta-Thalassemia_Draft-Report_041322.pdf
6. https://www.biopharma-reporter.com/Article/2022/06/13/FDA-advisory-vote-is-boost-for-bluebird-bio
7. http://www.cormedix.com/neutrolin/#:~:text=Defencath%E2%84%A2%20is%20a%20proprietary,infections%20from%20in%2Ddwelling%20catheters
8. https://www.pompecanada.com/blog/news/amicus-remains-hopeful-about-at-gaa-despite-mixed-results-from-phase-3-study/