Rakuten Medical to Start a Global Phase 3 Trial of Alluminox™ Treatment using ASP-1929 for Recurrent Head and Neck Cancer in India

SAN DIEGO, May 22, 2023 /PRNewswire/ -- Rakuten Medical, Inc. (Rakuten Medical), a global biotechnology company developing and commercializing precision, cell-targeting therapies based on its proprietary Alluminox™ platform, today announced that the Company has been granted permission from the Indian Central Drugs Standard Control Organization (CDSCO) to conduct its global, pivotal Phase 3 clinical trial (ASP-1929-301/ClinicalTrials.gov Identifier: NCT03769506) evaluating Alluminox treatment (photoimmunotherapy) using ASP-1929 in patients with locoregional, recurrent head and neck squamous cell carcinomas (HNSCC) in India, and the registration of clinical trial information with the Clinical Trial Registry of India (CTRI) has been completed (CTRI Identifier: CTRI/2023/05/052728). The study sites will include several leading medical institutions in India such as the Tata Memorial Centre and Narayana Health, and the treatment will be administered to enrolled patients once ready. This ASP-1929-301 study is currently underway in several countries such as the U.S. and Taiwan, and will enroll 275 patients globally including Indian patients.

In India, more than 200,000 new cases of head and neck cancer are diagnosed each year, which accounts for approximately 25% of all new head and neck cancer cases worldwide¹.  One of the reasons for this is the widespread use of chewing tobacco. More than 28% of all adults (15 years and above) in India are users of tobacco, and approx. 75% of them use smokeless tobacco, including chewing tobacco². It has been reported that more than half of oral cancer (a type of head and neck cancer) in India is attributable to smokeless tobacco, including chewing tobacco³. In addition to the high occurrence of head and neck cancer, it is known that the majority of these patients present with advanced disease, which also corresponds with poorer outcomes ⁴. Such high volumes of advanced stage patients can present many challenges for the surgeons and medical oncologists who treat head and neck cancer. Time and treatment options are limited. Surgery, radiation, and chemotherapy are all commonly used to manage this patient population – but more options are needed.

The multi-center, randomized, open-label, global Phase 3 study of Alluminox treatment using ASP-1929 will evaluate the efficacy and safety of ASP-1929 in patients with locoregional, recurrent HNSCC who have previously failed or progressed on or after at least two lines of therapy, of which at least one line must be systemic therapy, and are not eligible for surgery or radiation. Participants will be randomized to receive experimental therapy or investigator's choice of systemic therapy (2:1). The dual-primary endpoints of the study are progression-free survival and overall survival, and a key secondary endpoint includes objective response rate.

"We are very pleased to be conducting the pivotal Phase 3 study of Alluminox treatment using ASP-1929 in India, where there is a high unmet need for head and neck cancer treatment," said Mickey Mikitani, Co-CEO of Rakuten Medical.  "The addition of India to this important study will help to accelerate the development of this drug. We will continue to do our utmost to bring a new treatment option to patients with head and neck cancer around the world as soon as possible, working closely with medical institutions and regulatory authorities in each country."

ASP-1929 is a conjugation of an antibody cetuximab and IRDye® 700DX, a light activatable dye, and is Rakuten Medical's first pipeline drug developed on its Alluminox™ platform. It binds to epidermal growth factor receptor (EGFR), which is highly expressed in head and neck cancers. After binding to cancer cells, ASP-1929 is locally activated by non-thermal red light (690 nm) illumination, which leads to selective cell killing inpre-clinical observations. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the drug in January 2018. In Japan, in September 2020, ASP-1929 received marketing approval from the Ministry of Health, Labour and Welfare for unresectable locally advanced or recurrent head and neck cancer as brand name Akalux®, together with BioBlade® Laser System, the medical device used in combination with the drug under the Conditional Early Approval System. Outside of Japan, ASP-1929 and the laser device system have not yet been approved by any regulatory authority.

¹  Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2020). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed May 3, 2023

²  Global Adult Tobacco Survey (GATS) India Fact Sheet 2016-17. Centers for Disease Control and Prevention (CDC). https://www.tobaccofreekids.org/assets/global/pdfs/en/GATS_India_2016-17_FactSheet.pdf

³  Gupta PC, Arora M, Sinha DN, Asma S, Parascandola M (eds.); Smokeless Tobacco and Public Health in India. Ministry of Health & Family Welfare, Government of India; New Delhi; 2016. https://nhm.gov.in/NTCP/Surveys-Reports-Publications/Smokeless_Tobacco_and_Public_Health_in_India.pdf

⁴  Kulkarni MR. Head and Neck Cancer Burden in India. Int J Head and Neck Surg 2013;4(1):29-35 https://www.ijhns.com/doi/pdf/10.5005/jp-journals-10001-1132

* Rakuten Medical's therapies based on Alluminox™ platform are investigational outside of Japan, and not approved in India for commercial use.

About Rakuten Medical, Inc. 

Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting therapies based on its Alluminox™ platform, which, in pre-clinical studies, have been shown to induce rapid and selective cell killing and tumor necrosis. Alluminox therapies have not yet been approved outside of Japan. Rakuten Medical is committed to its mission to conquer cancer by delivering our innovative treatments as quickly as possible to as many patients all over the world as possible. The company has offices in 6 countries, including the United States, where it is headquartered, Japan, the Netherlands, Taiwan, Switzerland and India. For more information, visit www.rakuten-med.com.

About Alluminox™ platform  

The Alluminox™ platform is an investigational technology platform based on a cancer therapy called photoimmunotherapy, which was developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Rakuten Medical is developing the Alluminox platform as a technology consisting of a drug, device, and other related components. The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding. The device component consists of a light source that locally illuminates the targeted cells with non-thermal light to transiently activate the drug. Pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cancer cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Outside of Japan, Alluminox therapies have not yet been approved by any regulatory authority.

About ASP-1929

Rakuten Medical's first pipeline drug developed on its Alluminox™ platform is ASP-1929, an antibody-dye conjugate comprised of the antibody cetuximab and IRDye® 700DX, a light activatable dye. ASP-1929 binds to epidermal growth factor receptor (EGFR), a cancer antigen expressed in multiple types of solid tumors, including head and neck, breast,  lung, colorectal, prostate and pancreatic cancers. After binding to cancer cells, ASP-1929 is locally activated by non-thermal red light (690 nm) illumination emitted by a laser device system, resulting in photochemical reaction. This is believed to cause damage to the membrane of cancer cells, leading to selective necrosis of cancer cells. ASP-1929 has received Fast Track designation from the U.S. Food and Drug Administration (FDA) in January 2018, and is currently under investigation in a global Phase 3 clinical trial for recurrent head and neck cancer. In Japan, ASP-1929 received marketing approval from the Japanese Ministry of Health, Labor, and Welfare for unresectable locally advanced or recurrent head and neck cancer in September 2020, under the Sakigake Designation System and the Conditional Early Approval System. Outside of Japan, ASP-1929 has not yet been approved by any regulatory authority.

Forward Looking Statements  

This press release contains forward looking statements that correspond to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include various risks, uncertainties, and assumptions that may cause Rakuten Medical's business plans and results to differ from the anticipated results and expectations expressed in these statements. These "forward looking statements" contain information about the status and development of our products, including the Alluminox™ platform, as well as other regulatory and marketing authorization efforts, the potential benefits, efficacy, and safety of therapies created using the Alluminox platform, and the status of regulatory filings. The approval and commercial success of the product may not be achieved. Forward looking statements relate to the potential benefits, efficacy, and safety of our therapies, and the status of regulatory filings. Such statements may include words such as "expect," "believe," "hope," "estimate," "looks as though," "anticipate," "intend," "may," "suggest," "plan," "strategy," "will," and "do", and are based on our current beliefs. In addition, this press release uses terms such as "important," "notable," and "abnormal" to express opinions about clinical trial data. Ongoing clinical trial studies include various risks and uncertainties, in particular, problems that arise during the manufacturing stage of our therapies, the occurrence of adverse safety events, situations in failure to demonstrate therapeutic benefits, and other various risks and uncertainties, both reasonable and unreasonable. For this reason, actual results, including regulatory approvals and uncertainties in the commercialization process of our therapies, may differ from published information. Except to the extent required by applicable law, we undertake no obligation to publicly update this or any other forward-looking statement, whether because of new information, future developments or events, changes in assumptions, changes in the factors affecting forward-looking statements. If one or more forward-looking statement(s) is updated, no inference should be drawn that additional updates will be made to those or other forward-looking statements.

SOURCE Rakuten Medical, Inc.