Hemispherx Biopharma Releases Rintatolimod in EAP-program to Dutch Pancreatic Cancer Patients

Rintatolimod (Ampligen?; Hemispherx Biopharma) is a mismatched, double-stranded RNA molecule with immunomodulatory and antiviral properties. The drug acts as a Toll-like Receptor 3 (TLR3) agonists. [1] TLR3s have been extensively used as adjuvants for anticancer vaccines.

Rintatolimod stimulates the production of interferons and tumor necrosis factors and has shown to raise natural killer cell function.

In a statement, Hemispherx Biopharma the manufacturer of rintatolimod, announced that the company has released a batch of the drug, manufactured earlier this year,
for release to pancreatic cancer patients in an Early Access Program (EAP) in The Netherlands. This Early Access Program is managed by myTomorrows, a Dutch organization helping patients and doctors get access to novel therapeutic agents by reducing barriers to early access or compassionate use programs. The company doctors and their patients overcome regulatory, logistical, and financial hurdles to facilitate access to medicines in development around the world.

The company shipped initial shipment of 500 vials of a previously announced 2,100 vial standing stock order issued by myTomorrows.

Early Access Programs, also known as Expanded Access Programs or compassionate use programs, are market-specific regulatory programs in which certain governments allow companies to make a drug available with reimbursement approved before it is officially commercialized for serious or life-threatening diseases outside of a clinical trial ? if certain criteria are met ? with potential benefits both for patients and for drug development.

These government approved programs allow us to supply investigational drugs, while obtaining compensation through reimbursement.

?We have now manufactured approximately 16,000 vials of [Rintatolimod], with 8,000 vials tested and released for our various clinical and early access programs and the remaining vials are expected to be released in the near future,” said Thomas K. Equels, chief executive officer at Hemispherx.

“This begins the next logical step in our short term business plan, where we seek to obtain reimbursement, at pre-approved rates, for those vials by supplying early access programs in the United States for ME/CFS and in the Netherlands for pancreatic cancer, as well as the initiation of commercial sales from the second lot as a result of our unrestricted commercial approval for severe ME/CFS in Argentina,? Equels added.

Pancreatic Cancer
Rintatolimod is currently used in the Netherlands EAP in the treatment of pancreatic cancer. In addition, agent is being assessed for use in combination with checkpoint blockade therapies in a variety of solid tumors, including pancreatic cancer.

Clinical trials
In clinical trials in a variety of indications, approximately 100,000 doses of the investigational drug rintatolimod have been administered intravenously (IV).

According to experts, this is believed to be one of the most comprehensive IV safety profile that is generally well-tolerated of any systemic TLR agonist.

Toll-like receptors (TLRs) are a class of proteins that play a key role in activating the innate immune system and it is believed that they will play an important role in future combination therapies in immuno-oncology.

Long history
The development of rintatolimod has a long history. The drug is based on a double-stranded RNA (dsRNA) compound developed by the pharmaceutical company, Merck, in the 1960s, as a potential cancer drug. Although effective in the laboratory, the original compound proved to be too toxic for human use.

In the William Carter, MD, a researchers at Johns Hopkins University ? modified in the 1970s, reducing the toxicity of the drug.? Based on the drug’s AMPLIfied GENetic activity, Carter branded the drug Ampligen?. In the 1980w, through Hemispherx (then called HEM Research), Carter, then a researcher at Hahnemann University in Philadelphia, and several other researchers? at Hahnemann University, obtained a license for the compound and development technology from John Hopkins University.

Over time, Hemispherx Biopharma partnered with Dupont to start clinical trials for the development of rintatolimod.? However, with limited results, Dupont severed its business relationship with Hemispherx Biopharma.

“The availability of a growing number of checkpoint inhibitors has broadened the potential of rintatolimod in immuno-oncology beyond single-agent use. New data helps us to define the investigational agent’s potential role as a combinational agent in promoting killer T cell accumulation in the tumor microenvironment,” Thomas K. Equels explained.

Data presented by Pawel Kalinski MD, PhD from the Roswell Park Comprehensive Cancer Center during the 2018 Immuno-Oncology Frontiers Conference showed that combination rintatolimod had a positive modulating effect on the PD-1/PD-L1/PD-L2 system in human ovarian and colorectal cancer.

References
[1] Ming Lim C, Stephenson R, Salazar AM, Ferris RL. TLR3 agonists improve the immunostimulatory potential of cetuximab against EGFR+ head and neck cancer cells. Oncoimmunology. 2013;2(6):e24677. doi:10.4161/onci.24677.


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