Therapeutic focus - Shots on goal could be the key for lung cancer

Analysis

Should Novelos Therapeutics’ NOV-002 fail in its phase III trial for non-small cell lung cancer (NSCLC), the results for which are expected soon (Event – Pivotal lung cancer data could see Novelos soar, February 10, 2010) a large number of products are currently lining up to take over the baton in the race to become a new treatment option for this lethal condition. The R&D pipeline for lung cancer is flooded with candidates as big pharma and small biotech alike chase an indication for which a product, if authorised and shown to be better than therapies on the market, is almost certain to be a blockbuster.

A review of product portfolio data from EvaluatePharma indicates that there are 162 candidates in the late-stage pipeline (phase III/phase II) for all lung cancer indications. While natural R&D attrition means that many candidates will drop out having failed to show the efficacy or safety data that regulatory authorities demand, the sheer number of them suggests that some will hit their target and reach the market within the next few years. The entire pipeline from research project to phase III contains 300 candidates, as companies line up a significant number of shots on goal (see tables below).

Lung cancer - count of products
Status Count
Marketed 22
Phase III 34
Phase II 128
Phase I 54
Pre-clinical 68
Research project 16
Total 322

Lethal disease

It is an area of clear need. Caught in its earliest stages, the five-year survival rate for NSCLC, the most common type of lung cancer, is 49%. Yet by stage IV, the latest stage, five-year survival is just 1%, according to the American Cancer Society.

Use of Avastin, soon to be the world’s best-selling drug across all its uses, in combination with carboplatin and paclitaxel extends the life of patients with advanced NSCLC by about a year, compared with about 10 months for chemotherapy alone. A drug that can match or beat Avastin's efficacy or safety record is likely to be able to also beat its sales in that indication, estimated to be $1.18bn by 2014, according to new EvaluatePharmaestimates.

The big six lung cancer drugs - Avastin, Alimta, Tarceva, Taxotere, Iressa and Gemzar - got a bit of a breather in 2009 when the European Medicines Agency refused to authorize Merck KGaA to market Erbitux for NSCLC, while Bristol-Myers Squibb withdrew its application in the US because of manufacturing control issues. BMS maintains it plans to resubmit the US application, although Europe's rejection must reduce its chances of success.

Leading Marketed Products for Lung Cancer - sales across ALL approved indications, not just lung cancer WW annual sales ($m)
Product Generic Name Company Pharmacological Class Approved Indications 2009 2010 2012 2014
Avastin bevacizumab Roche Anti-VEGF MAb Colorectal cancer [Marketed]; Breast cancer [Marketed]; Non-small cell lung cancer (NSCLC) [Marketed]; Renal cell carcinoma (RCC) [Marketed]; Glioblastoma multiforme [Approved] 5,753 7,231 8,603 9,397
Alimta pemetrexed sodium Eli Lilly Thymidylate synthase inhibitor Mesothelioma [Marketed]; Non-small cell lung cancer (NSCLC) [Marketed] 1,706 2,158 2,812 3,237
Tarceva erlotinib hydrochloride Roche/OSI Pharmaceuticals EGFr antagonist Non-small cell lung cancer (NSCLC) [Marketed]; Pancreatic cancer [Marketed] 1,206 1,417 1,648 1,859
Taxotere docetaxel Sanofi-Aventis Taxane Breast cancer [Marketed]; Non-small cell lung cancer (NSCLC) [Marketed]; Ovarian cancer [Marketed]; Head & neck cancers [Marketed]; Stomach cancer [Marketed]; Oesophageal cancer [Marketed]; Prostate cancer [Marketed]; Endometriosis [Marketed] 3,096 2,992 1,700 1,077
Iressa gefitinib AstraZeneca EGFr & tyrosine kinase inhibitor Non-small cell lung cancer (NSCLC) [Marketed] 297 349 452 540
Gemzar gemcitabine Eli Lilly Pyrimidine analogue Pancreatic cancer [Marketed]; Non-small cell lung cancer (NSCLC) [Marketed]; Bladder cancer [Marketed]; Breast cancer [Marketed]; Ovarian cancer [Marketed]; Cervical cancer [Marketed]; Biliary cancer [Marketed] 1,363 1,234 724 294

Along with Erbitux in the late-stage pipeline, seven other phase III drugs are already in the market for other cancer indications: Velcade, Sutent, Nexavar, Abraxane, Vectibix, Eloxatin, and Camptosar. As Erbitux shows, however, effectiveness in some types of cancer does not guarantee a drug will pass muster in NSCLC.

In phase III a number of strategies are being applied: multi-kinase inhibitors, anti-EGFr MAbs, platinum compounds, EGFr/VEGF inhibitors and, among them, two cancer vaccines. For one of the vaccines, Merck KGaA’s Stimuvax, a new phase III trial was announced in December; the trial will enrol 420 Asian patients with inoperable stage III cancer, but will not report results until 2014.

With a rich vein to be mined in lung cancer, it comes as no surprise that the breadth of the pharmaceutical and biotech industry are chipping at the earth. The only question is which swing of the pick is going to bring forth the nuggets and how many will yield just fool’s gold.

Selected Phase III Candidates for Lung Cancer
Product Generic Name Company Pharmacological Class
Velcade bortezomib Johnson & Johnson/Takeda Proteasome inhibitor
Erbitux cetuximab Merck KGaA/Eli Lilly/Bristol-Myers Squibb Anti-EGFr MAb
Sutent sunitinib malate Pfizer Multi-kinase inhibitor
Nexavar sorafenib tosylate Bayer/Onyx Pharmaceuticals Multi-kinase inhibitor
Abraxane paclitaxel & albumin Abraxis BioScience Taxane
Vectibix panitumumab Amgen/Takeda Anti-EGFr MAb
Eloxatin oxaliplatin Sanofi-Aventis/Debiopharm Platinum compound
Camptosar irinotecan hydrochloride Pfizer Topoisomerase I inhibitor
Aflibercept (VEGF Trap) aflibercept Sanofi-Aventis/Regeneron VEGFr kinase inhibitor
ASA404/AS1404 (DMXAA) vadimezan Novartis/Antisoma Vascular targeting agent
CP-751871 figitumumab Pfizer Anti-IGF-1R MAb
Stimuvax - Merck KGaA/Oncothyreon Anti-MUC1 vaccine
MAGE-A3 ASCI astuprotimut-R GlaxoSmithKline Anti-MAGE-A3 vaccine
Picoplatin picoplatin Poniard Pharmaceuticals/Genzyme Platinum compound
Zactima vandetanib AstraZeneca EGFr & VEGFr inhibitor
PF-2,341,066 - Pfizer Met tyrosine kinase inhibitor
AMG 706 motesanib Amgen/Takeda VEGF, platelet-derived growth factor (PDGF) & c-kit tyrosine kinase inhibitor
Calsed amrubicin hydrochloride Celgene Anthracycline
Lucanix (L)-belagenpumatucel NovaRx TGF-beta inhibitor
MGd motexafin gadolinium Pharmacyclics Texaphyrin
NOV-002 glutathione disulfide Purdue Pharma/Novelos Therapeutics Chemotherapy protector
Opaxio paclitaxel poliglumex Cell Therapeutics/Novartis Taxane
Targretin bexarotene Eisai/Cephalon Retinoid X receptor agonist
Telcyta (TLK286) canfosfamide hydrochloride Telik Alkylating agent
Tovok - Boehringer Ingelheim EGFr & HER2 (ErbB-2) dual kinase inhibitor
Vargatef - Boehringer Ingelheim Triple angiokinase inhibitor

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