The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for disitamab vedotin (previously known as RC48), for the second-line treatment of patients with human epidermal growth factor receptor-2 (HER2) positive locally advanced or metastatic urothelial cancer (mUC) who have also previously received platinum-containing chemotherapy treatment.

Jianmin Fang, Ph.D., founder, Chief Executive Officer, and Chief Scientific Officer of RemeGen (Yantai, Shandong Province, China) and Chairman of MabPlex (Yantai, Shandong Province, China) received his Ph.D. in Microbiology and Bioreaction Engineering from Nagoya University, Japan. Fang has 30 years of biopharmaceutical industry experience managing biologics development and cGMP manufacturing and oversaw hundreds of successful regulatory submissions and USFDA/EMA site inspections He also held key product development roles at BMS, J&J, Immunomedics, SAFC/MilliporeSigma, and Phage Biotechnology and lead the fast track commissioning of several cGMP facilities/operations in the United States, Europe, and Asia from clinical- to commercial manufacturing.

Disitamab vedotin selectively delivers anti-cancer agent monomethyl auristatin E (MMAE) into HER2+ tumor cells and is a novel antibody-drug conjugate or ADC being developed by RemeGen (Yantai, Shandong Province, China).

Its novel antibody has a higher affinity to the HER2 oncogene compared to the standard of care and, in animal models, demonstrates superior anti-tumor activity compared to other treatments.

Disitamab vedotin was the first ADC drug approved for human clinical trials in China and a favorable safety profile has been observed in clinical trials. Overall, the trial drug is well-tolerated and has shown significant anti-tumor activities in a number of HER2+ cancer, including in some HER2 low expressors (IHC +2, FISH negative patients).

It is currently being studied in multiple late-stage clinical trials across solid tumor types.

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Earlier this year, RemeGen announced the FDA’s clearance of an Investigational New Drug (IND) application for a Phase II clinical study in the United States and the grant of Fast Track designation for disitamab vedotin.

A drug development program with Breakthrough Therapy designation is eligible for all Fast Track designation features, intensive guidance on an efficient drug development program beginning as early as Phase I, and organizational commitment involving senior managers. This process is designed to expedite the development and review process.

Incidence of Urothelial cancer
“An estimated 81,400 new cases of urothelial cancer and 17,980 deaths are predicted in the United States in 2020,” said Jianmin Fang, Ph.D., founder, Chief Executive Officer and Chief Scientific Officer of RemeGen.[1]

The prevalence of urothelial cancer, in conjunction with its vulnerability to multiple recurrences and progression despite local therapy, leads to a substantial burden to health service.[2]

“[This] high prevalence of metastatic urothelial cancer underscores the need for effective and accessible treatment methods for patients. This Breakthrough Therapy designation will bring RemeGen one step closer to finding a safe and effective treatment for this devastating disease. We look forward to working with the FDA to advance the clinical development of disitamab vedotin,” Fang concluded.

Urothelial cancer represents the ninth most common cancer worldwide and the fourth most common cancer in men in the United States.[2]

Clinical trials
A Phase II Study of RC48-ADC in Subjects With HER2 Positive Metastatic or Unresectable Urothelial Cancer – NCT03507166
A Study of RC48-ADC(Antibody Drug Conjugate) and JS001 to Evaluate the Safety and Pharmacokinetics of Subjects With Locally Advanced or Metastatic Urothelial Cancer – NCT04264936
A Study of RC48-ADC in Subjects With HER2-negative Locally Advanced or Metastatic Urothelial Cancer – NCT04073602
An Open-label, Single-arm, Multicenter, Phase II Study of RC48-ADC to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer – NCT03809013

References
[1] National Cancer Institute. Cancer Stat Facts: Bladder Cancer. 2020. Online. Last accessed on September 25, 2020.
[2] The Global Epidemiology of Bladder Cancer. Scientific Reports 2018. Nature.com. Online. Last accessed on September 25, 2020

An edited version of this article was published in ADC Review | Journal of Antibody-drug Conjugates.

Featured image: Bladder Cancer.

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