Clavis Pharma and Clovis Oncology sign $380 million deal for anti-cancer agent CP-4126

Article | 26 November 2009

Norwegian oncology focussed Clavis Pharma and USA-based Clovis Oncology, the newly-formed oncology company led by former Pharmion Corp executives, have an agreement for the further development and commercialization of the Clavis Pharma drug candidate, CP-4126, currently in Phase II development in pancreatic cancer. CP-4126 is a novel, patented, lipid-conjugated form of the anti-cancer drug gemcitabine that has the potential to improve treatment outcomes in a large subset of patients with pancreatic cancer and certain other solid tumours.

The deal provides for Clavis to receive an upfront cash payment of $15 million from Clovis and will be eligible for further payments totalling up to $365 million on Clovis’ successful attainment of development, regulatory and sales milestones. Clavis will be eligible for tiered double-digit royalties on all product sales in the licensed territories.

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Under the terms of the accord, Clovis will take over responsibility for product development and manufacturing of CP-4126, and for filing of marketing approvals in the USA, Europe, Canada, Central and South America and will be responsible for commercialisation in those territories. Clavis Pharma retains the option to co-develop and co-promote CP-4126 in Europe.

The companies are amending the design of the ongoing Phase II study in pancreatic cancer to enroll approximately 250 patients in an international, randomized, comparative trial of CP-4126 versus gemcitabine with overall survival as a primary endpoint.

In addition to evaluating survival in all patients, study results will be analysed based on patient classification in relation to their levels of expression of the hENT1 pancreatic tumour protein. The hENT1 (human equilibrative nucleoside transporter 1) cell membrane transporter is believed to be critical for gemcitabine entry into tumor cells, whereas CP-4126 enters and kills tumor cells in a hENT1-independent manner. Patients will be classified as being hENT1-high or hENT1-low and particular emphasis will be given to comparative overall survival in the hENT1-low population. Data from this trial are expected in the first half of 2012.

Commenting on the deal, Geir Christian Melen, chief executive of Clavis, noted that Clovis has “substantial experience of successful cancer drug development and marketing and will bring significant resources, expertise and commitment to the conduct of the CP-4126 clinical program and achieving regulatory approvals in these major markets. We view this agreement as an important validation of Clavis Pharma’s potential to generate multiple novel cancer drugs with enhanced performance over existing therapeutics. This strategic partnership for CP-4126, our second product under development, will enable us to focus resources on developing our portfolio further and provides great momentum towards our building a successful oncology business.”

Patrick Mahaffy, president and CEO of Clovis, added: “Gemcitabine is the standard of care in pancreatic cancer, but accumulating data suggest that a significant percentage of patients may derive little benefit from its use because of low expression of the hENT1 transporter that allows gemcitabine to enter tumor cells. In vitro data demonstrate that CP-4126 overcomes this resistance mechanism. We now have the opportunity to show that a cytotoxic, which remains the backbone of cancer therapy, can become an effective, targeted therapy in this large subset of patients. Our development philosophy is to focus on providing meaningful benefit to subset patient populations with unmet medical need and we believe CP-4126 will do exactly that.”

About CP-4126

CP-4126 is a new, patented, cytotoxic drug, consisting of an anti-cancer nucleoside analogue coupled to a lipid chain. It was generated using Clavis’ proprietary Lipid Vector Technology and has been designed to improve the therapeutic profile of gemcitabine (Gemzar, marketed by US drug major Eli Lilly) so that it can enter cancer cells without requiring uptake by a specific transporter molecule. Other potential indications for CP-4126 are those currently treated with gemcitabine, including lung, breast, ovarian and bladder cancer. An oral formulation of CP-4126 is currently in a Phase I clinical trial in pancreatic cancer.

In August, a Michigan federal court ruled in favor of Sun Pharmaceuticals, invalidating Lilly's method of use patent for its cancer drug Gemzar, which is not set to expire until 2013. Lilly continues to hold the compound patent for the drug, an injectible, that generated $1.7 billion in worldwide sales in 2008.

Icelandic generic drug firm Actavis launched a copy product in March, and Lilly is already facing competition in Europe. Also, Israeli generic giant Teva’s US subsidiary, Sicor, filed an Abbreviated New Drug Application in the USA at the beginning of this year.

Lilly saw worldwide sales of Gemzar fall 17% to $721 million in the first half of 2009. In its statement on the Michigan court ruling. The company reassured investors that the decision “does not make way for generic competition in the USA just yet,” and will appeal the ruling.