FDA Grants Orphan Drug Designation to AVS100 for Stage IIB-IV Melanoma

Pipeline Report: November 2022

The FDA has granted an orphan drug designation to the highly specific HDAC6 inhibitor AVS100 for the treatment of patients with stage IIB to IV melanoma.

Vishal Patel, MD, FAAD, FACMS

Vishal Patel, MD, FAAD, FACMS

The FDA has granted an orphan drug designation (ODD) to the highly specific HDAC6 inhibitor AVS100 for the treatment of patients with stage IIB to IV melanoma, according to an announcement from Avstera Therapeutics.1

“The FDA’s grant of this ODD for AVS100 highlights the significant unmet need there remains for this patient population and the impact our therapy can have in potentially improving clinical outcomes. Advanced stage melanoma remains a complex and difficult cancer to treat with current approaches, and AVS100 has the potential to provide an opportunity to potentially reduce the disease burden shared by these patients,” Karthik Musunuri, chief executive officer and co-founder of Avstera Therapeutics Corp, said in a press release.

In metastatic melanoma, only 20% to 30% of patients derive benefit from anti–PD-1 inhibitors.2 In preclinical in vivo models, AVS100 downregulated PD-L1 expression, reduced tumor growth, and led to an increase in overall survival and the overall M1/M2 macrophages in the tumor microenvironment.

Macrophage differentiation and stabilization of M1 is crucial in maintaining antitumor activity. AVS100 is a novel, highly specific, small molecule HDAC6 inhibitor that polarizes macrophages to the anti-tumoral M1 phenotype.

Through this mechanism, it is theorized that AVS100 can elicit synergistic responses with immunotherapy, broadening the population of patients who may benefit from treatment.

“The use of selective HDAC6 inhibitor treatment is an exciting approach to manipulate the tumor microenvironment and prime the host to increase the therapeutic response to checkpoint inhibitor therapy. This provides hope to patients who may have progressed on single-agent treatment and are looking to boost response, or those unable to tolerate dual immunotherapy for refractory or more advanced cases,” Vishal Patel, MD, FAAD, FACMS, director of the Cutaneous Oncology Program at the George Washington Cancer Center and member of Avstera’s scientific advisory board, added.

AVS100 remains on track for the company’s planned investigational new drug filing in 2023 for patients with locally advanced or metastatic solid tumors, including melanoma.


  1. Avstera Therapeutics Receives FDA Orphan Drug Designation on AVS100 for Treatment of Advanced Stage Melanoma. News release. Avstera Therapeutics. November 11, 2022. Accessed November 17, 2022. https://prn.to/3Gp0Z8F
  2. Pipeline. Avstera Therapeutics Corp. Accessed November 17, 2022. https://avstera.com/pipeline/
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