Pancreatic Cancer Dealt Blow but Large Mid-Stage Pipeline Holds Hopes

February 02, 2009 Pancreatic cancer dealt blow but large mid-stage pipeline holds hopes

Amy Brown

The failure of Pfizer’s axitinib in a phase III trial in pancreatic cancer is a big disappointment, considering the drug was one of the most promising-looking new therapies in a very challenging field.

Five years after diagnosis only 5% of pancreatic cancer patients are still alive, and effective treatment options are limited. Only two drugs are widely used, standard of care Gemzar, made by Eli Lilly, and Roche and Genentech’s Tarceva. A look at what is in development is fairly encouraging, however, with a healthy looking mid-stage pipeline that will hopefully yield new treatments in the not too distant future (see table below). According to EvaluatePharma there are 78 products in phase II and III trials, meaning numerous shots on goal are possible.

The following table details drugs that are not yet approved for any indication, and have pancreatic cancer as one of their primary indications under development. Other successful drugs already on the market such as Avastin, Erbitux and Xeloda are also in phase III trials for the cancer, and could also prove to be effective treatments.

Pancreatic cancer pipeline - selected NME drugs (sales aggregated across ALL WW annual indications in development) sales ($m)

Year of Phase Product Company (s) Pharmacological Class 2010 2014 launch

Phase Axitinib (AG- Pfizer VEGFr kinase inhibitor 2009 103 789 III 13,736)

Rapamycin analogue (mTOR Afinitor Novartis 2010 98 227 inhibitor)

Sanofi-Aventis + Aflibercept Regeneron VEGFr kinase inhibitor 2012 12 182 (VEGF Trap) Pharmaceuticals

Larotaxel Sanofi-Aventis Taxane 2010 23 103 (XRP9881)

GV1001 Pharmexa Anti-telomerase vaccine - - -

Threshold Pharmaceuticals Glufosfamide Alkylating agent - - - + Baxter International

RP101 RESprotect Hsp27 inhibitor - - -

PN401 Wellstat Therapeutics Uridine - - -

Phase AVN944 (VX- Avalon Pharmaceuticals + Inosine monophosphate 2011 - 145 II 944) Vertex Pharmaceuticals dehydrogenase inhibitor

ARQ 197 ArQule + Daiichi Sankyo Tyrosine kinase inhibitor 2011 - 118

Anti-MUC1 MAb-yttrium 90 IMMU-107 Immunomedics - - - conjugate

SuperGen + AVI SuperGen + AVI Avicine Anti-hCG vaccine - - - BioPharma

AMG 655 Amgen + Takeda Anti-TRAIL-R2 MAb - - -

MORAb-009 Eisai Anti-GP IX MAb - - -

EndoTAG-1 MediGene Angiogenesis inhibitor - - -

GVAX Cell Genesys Pancreatic cancer vaccine - - - Pancreas

MetXia Oxford BioMedica CYP2B6 gene therapy - - -

PX-12 Oncothyreon Thioredoxin inhibitor - - -

Urokinase-specific Mesupron Wilex plasminogen activator (uPA) - - - inhibitor

BrevaRex Paladin Labs Anti-MUC1 MAb - - -

Anti-CEA MAb-iodine 131 XR303 Celtic Pharma - - - conjugate

RP101 SciClone Pharmaceuticals Nucleoside analogue - - -

RAV12 MacroGenics Anti-RAAG12 MAb - - -

ARC 100 Archer Biosciences Microtubule inhibitor - - -

GI-4000 GlobeImmune Ras vaccine - - -

RTA 402 Reata Pharmaceuticals Anti-inflammatory agent - - -

Of these drugs in development, axitinib was the most advanced and highly encouraging phase II data had raised hopes. That leaves Novartis’ Afinitor, a novel mTOR inhibitor which created a lot of interest at last year’s ASCO conference, as one to watch.

The axitinib news could be causing worries at Regeneron Pharmaceuticals, considering aflibercept is also a VEGF inhibitor and will have the same mode of action. However the drug, partnered with Sanofi-Aventis, is in phase III trials for multiple cancer types so still has several chances of success.

Further away but also provoking interest is ArQule's ARQ 197, which it partnered with Daiichi Sankyo last November. The drug is a cMET inhibitor, a class of drug that is emerging as an important source of targeted cancer therapies, and ARQ 197 is one of the most advanced in development (Poor response to ArQule deal illustrates market's refusal for optimism, November 12, 2008).

Another phase II candidate that has generated significant interest is MediGene's EndoTAG-1, which produced positive phase II results last October (MediGene moving into crucial partnership phase, October 20, 2008). A long-awaited licensing deal has caused much speculation about potential partners, with Eli Lilly and Pfizer most frequently named as interested parties. With Eli Lilly already owning standard of care for pancreatic cancer Gemzar, but with the drug set to lose patent protection next year, the strategic rationale is clear.

Whether Pfizer is still interested after today's disappointment with axitinib remains to be seen, but in a press release the company said it remained committed to finding new treatments for the cancer. This could mean a deal for MediGene is not too far away, and with the most promising pancreatic drug now struck off the list, the German biotech's negotiating arm could be stronger.