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 is a novel humanized anti-HER2 antibody-drug conjugate (ADC) being developed by RemeGen (Yantai, Shandong Province, China) designed to treat HER2 expressing solid tumors. It has a novel antibody with a higher affinity to HER2 compared to standard of care, and superior antitumor activity compared to other treatments in animal models.

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

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.

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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]

Disitamab Vedotin is also investigated in other solid tumor indications.

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

[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. Online. Last accessed on September 25, 2020

An edited version of this article was published in Onco’Zine.

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