Human kidney cross section. Photo courtesy: 2019 Fotolia
Human kidney cross section. Photo courtesy: 2019 Fotolia

The United Kingdom-based Clinigen Group has bought the global rights to Proleukin?, also known as Aldesleukin (recombinant interleukin-2; rIL2) outside the USA from Swiss Pharmaceutical company Novartis. Financial details of the agreement have not been disclosed.

Indication
Initially called T cell growth factor or TCGF, Interleukin-2 (IL-2), a type of cytokine signaling molecule, was one of the first interleukins to be characterized.? Its activity was detected in the supernatant of mitogen-stimulated peripheral blood lymphocytes. Following discovery, IL-2 was recognized as a central factor in controlling the immune response.[1]

Interleuking-2 has an unique place in medical history. It was the first type I cytokine that was cloned, the first type I cytokine for which a receptor component was cloned, and was the first short-chain type I cytokine whose receptor structure was solved. [1]

Aldesleukin, a form of recombinant interleukin-2 (rIL2) with the alanine removed from its N-terminal and residue 125 replaced with serine, is manufactured using recombinant DNA technology and is marketed as a protein therapeutic branded as Proleukin.

Licensing
Proleukin is licensed in 20 countries around the world and is primarily indicated for use in metastatic renal cell carcinoma (metastatic RCC), also called kidney cancer. The disease occurs when cancer cells form in the tubules – the tiny tubes in the kidney that help filter waste products from blood in order to make urine. Generally, smoking, hypertension, obesity, and hepatitis C are factors that increase the risk of renal cell carcinoma. Renal cell carcinoma becomes metastatic renal cell carcinoma when it spreads beyond your kidney to your lymph system, bones, or other organs.

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In certain markets Proleukin is also indicated for the treatment of metastatic melanoma, the rarest and most dangerous type of skin cancer. Melanoma begins in the melanocytes, which are the cells in the skin that produce melanin, the pigment responsible for skin color. Melanoma develops into growths on the skin, which often resemble moles. These growths or tumors may also come from existing moles. Melanomas can form on skin anywhere on your body, including inside the month or vagina.

In addition, Proleukin is currently being investigated in clinical trials at varying dose levels and in combination with other licensed and developmental pharmaceutical products.

Evaluation of clinical studies to date reveals that patients with more favorable ECOG performance status (ECOG PS 0) at treatment initiation respond better to Proleukin, with a higher response rate and lower toxicity. Therefore, selection of patients for treatment should include assessment of performance status.

Photo 1.0: Proleuking packaging.

Revitalize sales
The Clinigen Group will ?seek to revitalize sales of Proleukin,? by boosting field force efforts and by leveraging its global distribution network. The company will also consider developing new dosage presentations and product combinations.

The acquisition of Proleukin? is a good fit with the Group?s current Commercial Medicines portfolio of products in the oncology and infectious disease therapy areas.

?This acquisition strengthens our offering in Commercial Medicines and brings our specialty pharma product portfolio to six,? said Shaun Chilton, chief executive officer of the company.

“It demonstrates our strategy of acquiring global rights to assets with the aim of revitalising and returning them back to the broadest possible access, whilst also supporting their use in new and emerging treatment regimens,” Chilton added.

“Proleukin is an important medicine that has demonstrated complete responses in some patients, with evidence of cancer free survival over 15 years. We believe that its use in emerging treatment regimens will continue to help people fight cancer for years to come,” David Bryant, Chief Business Officer of Clinigen concluded.

A short history
Proleukin was original developed by Ceutus Corporation, one of the first biotechnology companies established in Berkley, CA, in 1971 by Ronald E. Cape, Peter Farley, and Nobel laureate Donald A. Glaser.

In the early 1980s Cetus, Genentech, Immunex (now part of Amgen), and a Japanese researcher called Tadatsugu Taniguchi, competed to clone the gene for Interleukin-2. In 1982 Taniguchi was the first to succeed. A year later, in 1983 Cetus, created a proprietary recombinant human version of interleuking-2 with essentially similar pharmacodynamic properties as natural interleukin-2 and collaborated with Steven Rosenberg to begin clinical trials.

Aldusekeukin, as recombinant interleuking-2 was named, showed promising effects in treating renal cancer, but also had significant side effects on patients. By 1990 aldesleukin was approved in nine European countries.? However, the U.S. Food and Drug Administration (FDA) refused to approve the drug for clinical use, asking for additional information. Eventually, the drug was approved in 1992, after Cetus, and it’s European subsidiary EuroCetus, had been sold to Chiron Corporation (in 1991).

Chiron, founded in 1981 by William J. Rutter, Edward Penhoet, and Pablo DT Valenzuela, further developed aldesleukin and marketed as Proleukin. By 1993 Proleukin was the only approved version of rIL-2 marketed. However, other companies developed their own versions of the protein. Roche was developed a proprietary, modified, recombinant IL-2 called teceleukin, with a methionine added at is N-terminal, and Glaxo developed a version called bioleukin, with a methionine added at is N-terminal and residue 125 replaced with alanine.

Following the merger between Sandoz Laboratories and Ciba-Geigy in 1996, the newly established Novartis Corporation owned slightly less than half of Chiron. In 2005, Novartis made an offer to buy the entire company. This attempt was initially rebuffed, but after the bid was substantially enhanced, Chiron was sold, and became part of Novartis in April, 2006. The all-cash deal represented a total value of US $ 5.4 billion. In 2013 Novartis divested most of the former Chiron assets as part of a global reorganization.

In the United States Proleukin is distributed by Prometheus Laboratories, San Diego, CA, a devision of Soci?t? des Produits Nestl? S.A. Vevey, Switzerland.

Reference
[1] Th?ze J, Interleukin 2. Encyclopedia of Immunology (Second Edition), 1998


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