Satraplatin [BMS 182751, BMY 45594,
JM 216] belongs to a series of orally-active
platinum compounds with anticancer activity. It was jointly originated by Bristol-Myers Squibb, Johnson Matthey and the Institute of
Cancer Research in the UK; however, Johnson Matthey has since ceased involvement with
drug development. Subsequently, the agent has been licensed to and is under development with GPC Biotech, Pharmion and Spectrum
Pharmaceuticals. Clinical trials are underway to evaluate
satraplatin among patients with different tumour types, including prostate, breast, cervical and
lung cancers. The compound is under regulatory review with the US FDA for the treatment of
hormone-refractory
prostate cancer. NeoTherapeutics (now Spectrum
Pharmaceuticals) granted GPC Biotech an exclusive worldwide licence to develop and market
satraplatin in October 2002. Under the terms of the agreement, GPC Biotech is fully funding development costs and commercialisation requirements for the
drug. The deal also involves GPC Biotech paying a signing fee, milestone and royalty payments. Spectrum is a member of a joint development committee headed by GPC Biotech to govern development of
satraplatin. Previously in October 2001, NeoOncoRx (Spectrum
Pharmaceuticals) gained the rights to develop and market the compound worldwide. In December 2005, GPC Biotech and Pharmion Corporation entered into a co-development and license agreement for
satraplatin. Under the agreement terms, Pharmion has exclusive commercialisation rights for Europe, Turkey, the Middle East, Australia and New Zealand, while GPC Biotech retains rights to North America and all other territories. Pharmion made an upfront payment of $US37.1 million to GPC Biotech, which included reimbursement for past clinical development costs plus funding for ongoing and certain clinical development activities to be jointly conducted by the companies. In addition, both parties will pursue a joint development plan for
satraplatin in a variety of tumour types and will share global development costs, for which Pharmion has made an additional commitment of $US22.2 million. GPC Biotech could also receive up to $US270 million in milestone payments and royalties on sales. Both companies will manage regulatory and commercial activities in their respective territories. A registrational phase III study is ongoing among 950 patients with HRPC. This global, multicentre, randomised study, called SPARC (
Satraplatin and
Prednisone Against Refractory
Cancer), is assessing
satraplatin plus
prednisone versus
prednisone alone as second-line
therapy in HRPC patients. Top-line results from the trial showed that patients who received
satraplatin plus
prednisone had a 40% reduction in the risk of progression compared with patients who received
prednisone plus placebo. In accordance with the recommendation of the independent Data Monitoring Board for the SPARC trial, patients who have not progressed will continue to be treated and all patients will be followed for overall survival. The company expects to have final overall survival results in the fall of 2007. The company intends to complete the NDA filing with the FDA before the end of 2006. In February 2006, GPC Biotech raised euro36.2 million from a private placement of shares; the funds will be used in the commercialisation of
satraplatin in the US. GBC Biotech received a Scientific Advice letter from the EMEA in January 2004, enabling the company to use the SPARC trial for registrational plans in both Europe and the US. Data from the pivotal phase III trial are expected in the second half of 2006. If positive, the findings will form the basis of a MAA filing with the EMEA for
satraplatin as a second-line
therapy of HRPC. The EMEA has confirmed that it would accept the final analysis for progression-free survival (PFS) from the SPARC trial and the available overall survival data as the basis for the MAA submission expected in the first quarter of 2007. In December 2005, enrolment started for a phase II study of
satraplatin plus
paclitaxel as a first-line treatment for unresectable advanced NSCLC. This open-label study is enrolling up to 40 patients at sites in the US. In addition, GPC Biotech and Spectrum have initiated a phase I/II trial of
satraplatin plus
radiation therapy among patients with NSCLC. The study is expected to enrol up to 30 patients in the phase I portion to determine dose-limiting toxicities and maximum tolerated doses. Once these are established, the phase II portion will enrol patients to evaluate efficacy and safety. This trial is expected to be closely followed by phase I/II trials of
satraplatin in combination with
docetaxel and
paclitaxel. GPC Biotech initiated a phase I trial in July 2005 investigating
satraplatin plus
docetaxel among patients with advanced solid tumours in the US. The study is primarily focused on establishing the toxicity and maximum tolerated doses of combination
therapy to determine suitable dosages for phase II trials. Enrolment is ongoing for the open-label, single-centre study with a target of up to 48 patients. A phase I study is evaluating
satraplatin in combination with
gemcitabine in patients with advanced solid tumours. Previously, Bristol-Myers Squibb initiated phase III development of
satraplatin in Europe and the US in 1996. The trials were being conducted in patients with ovarian, non-small cell lung and small-cell
lung cancers. However, the company closed all ongoing trials of
satraplatin in 1999.
Satraplatin is protected by a number of patents issued in the US, EU, Japan, Canada and Australia. The patents have been assigned to Johnson Matthey, a multinational chemical company in the UK, which has exclusively sub-licensed these to GPC Biotech under a co-development and licensing agreement with Spectrum
Pharmaceuticals. The patents cover the composition of matter and anticancer uses of various
platinum-based compounds, including
satraplatin. Two of the US patents will expire in 2008 and 2010, respectively, while patents in most other countries will expire in 2009.