- 65 percent of the initial 250 patients enrolled in the study are hENT1-low
- Percentage consistent with retrospective analyses (002 study) performed from other pancreatic cancer studies
- Confirms LEAP trial is robust and well powered
Oslo, Norway. 9 January 2012
Clavis Pharma ASA (OSE: CLAVIS) announces that its partner Clovis Oncology, Inc. (NASDAQ: CLVS) has been informed by the Independent Data Monitoring Committee (IDMC) for the LEAP [1] pivotal trial of CP-4126 in metastatic pancreatic cancer, that approximately 65 percent of the enrolled patients have been classified as hENT1-low (see also separate release by Clovis Oncology). CP-4126 (also known as CO-101) was licensed by Clovis Oncology from Clavis Pharma in 2009 in a development and commercialization agreement worth up to $585 million.
The analysis is based on 250 patients enrolled in the study through late October 2011, representing over two-thirds of the planned 360 patients expected to be enrolled in the study. The hENT1-low patients are the target population for CP-4126, the Company’s lipid-conjugated gemcitabine. LEAP is an international, randomized, controlled 360-patient, pivotal trial designed to demonstrate that CP-4126 improves overall survival versus gemcitabine in hENT1-low metastatic pancreatic cancer patients. LEAP is expected to be fully enrolled at the end of the first quarter 2012 with first results expected to be reported by the end of 2012.
Olav Hellebø, Clavis Pharma CEO, said: "The information on the hENT1 status of the LEAP study population is very encouraging and confirms what we saw from the retrospective 002 study, that up to two thirds of pancreatic cancer patients are likely to be hENT1-low. This information also demonstrates that we have a sufficiently large patient population and thus a well-powered study on which to base a regulatory filing if it is positive.”
The hENT1 Hypothesis
The standard first-line treatment for patients with metastatic pancreatic cancer is gemcitabine, given either as monotherapy
or in combination with other cytotoxic agents. For gemcitabine to kill cancer cells, it must enter through specific membrane
transporters on the surface of the cells, and human Equilibrative Nucleoside Transporter 1 (hENT1) has been shown to be the
dominant transporter for gemcitabine. Tumour cells with low hENT1 expression have been shown to be resistant to gemcitabine
therapy in vitro and in vivo, and retrospective analyses from multiple published studies of gemcitabine in pancreatic cancer have shown a strong correlation
of overall survival outcomes to hENT1 expression, with patients that have low hENT1 expression receiving effectively no benefit
from gemcitabine therapy. LEAP is the first trial that seeks to prospectively demonstrate this important correlation.
About the hENT1 Companion Diagnostic Test
Clavis Pharma’s partner, Clovis Oncology has established a collaboration with Ventana Medical Systems, Inc. to develop an
in vitro diagnostic (IVD) to reliably measure tissue hENT1 expression and enable prospective classification of patients as either
hENT1-high or hENT1-low. Clovis utilized this IVD to establish the definition of hENT1-high and hENT1-low patients from a
number of clinical studies of gemcitabine, all of which demonstrated that the percentage of hENT1-low patients was approximately
two-thirds (002 study). This percentage has now been prospectively confirmed in LEAP. As part of the development plan for
CP-4126, Clovis and Ventana have completed the necessary analytical validation studies for the IVD, and it is currently undergoing
clinical validation in LEAP
. Ventana intends to submit the Pre-Market Approval Application (PMA) in coordination with Clovis’ New Drug Application (NDA)
for CP-4126.
About CP-4126
CP-4126 (also known as CO-101) is a novel, patented, lipid-conjugated form of the anti-cancer drug gemcitabine. In contrast
to gemcitabine alone, CP-4126 was designed to enter cancer cells regardless of hENT1 expression. CP-4126 is intended to address
the unmet need of patients with pancreatic cancer whose tumours express low amounts of hENT1 and therefore, are expected to
be resistant to standard gemcitabine therapy.
About LEAP
LEAP is an international, randomized, controlled 360-patient, pivotal trial designed to demonstrate that CP-4126 improves
overall survival versus gemcitabine in hENT1-low metastatic pancreatic cancer patients. Patients enrolled in the trial are
being randomized on a one-to-one basis to receive either CP-4126 or gemcitabine. Metastatic tumour tissue is collected from
all patients to enable hENT1 assessment, although the sponsors will remain blinded to each patient’s hENT1 status until the
end of the study when the primary analysis is completed. The study is designed to show that CP-4126 has superior efficacy
to gemcitabine in hENT1-low patients, in whom gemcitabine is believed to be minimally active.
About Pancreatic Cancer
According to the American Cancer Society, over 43,000 new cases of pancreatic cancer occurred in the United States in 2010.
In addition, according to Pancreatic Cancer Action Network, over 60,000 new cases are reported each year in the European Union
and according to a study published in Cancer Chemotherapy and Pharmacology in 2004, over 20,000 new cases are reported annually in Japan. According to Medical, Surgical & Radiation Oncology (9
th
Edition, 2005), 85 percent of patients with pancreatic cancer present with unresectable, locally advanced (Stage III), or
metastatic (Stage IV) disease. Even after surgical resection and adjuvant chemotherapy or radiotherapy for apparently localized
disease, these patients often experience early recurrence and rapid disease progression. As a result, according to the American
Cancer Society, pancreatic cancer has one of the highest mortality rates among all cancers, with estimates for one- and five-year
overall survival of 24 and 5 percent, respectively, in the United States.
For further information contact:
Olav Hellebø
Chief Executive Officer
+47 24 11 09 50
olav.hellebo@clavispharma.com
Gunnar Manum
Chief Financial Officer
+47 24 11 09 71
+47 95 17 91 90 (mob)
gunnar.manum@clavispharma.com
Mark Swallow / Nina Enegren / David Dible
Citigate Dewe Rogerson
+44 207 282 2948
clavispharma@citigatedr.co.uk
About Clavis Pharma
Clavis Pharma ASA is a late clinical stage oncology discovery and drug development company based in Oslo, Norway with a portfolio
of novel anti-cancer drugs in development. These patented New Chemical Entities (NCEs) are novel, improved versions of commercially
successful drugs, made using Clavis Pharma's Lipid Vector Technology (LVT) chemistry. Data generated suggests these potential
breakthrough products may offer improved efficacy and reduced side effects through enhanced pharmacokinetic properties, greater
tissue penetration, altered metabolism and, in certain cases, additional modes of action.
Clavis Pharma's has several drug candidates in formal development studies:
- Elacytarabine, a leukaemia drug, currently in a randomized, controlled Phase III study in late-stage acute myeloid leukaemia;
- CP-4126, is currently in a pivotal clinical study compared to gemcitabine for the 1st line treatment of pancreatic cancer and a Phase II trial for 2nd line treatment for pancreatic cancer in patients refractory to 1st line gemcitabine treatment;
- CP-4200, an azacitidine derivative, in preclinical development for myelodysplastic syndrome (MDS), a disease that is often a precursor to leukaemia.
Clavis Pharma intends to commercialise its products through strategic alliances and partnerships with experienced oncology businesses and, where and when commercially appropriate, by establishing its own sales and marketing capabilities.
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[1]LEAP - L ow h E NT1 and A denocarcinoma of the P ancreas