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Ariad’s ALK inhibitor could be a huge step forward in lung cancer treatment.

Guillermo Herrera - Tuesday, June 28, 2011

One year ago, an anaplastic lymphoma kinase (ALK) inhibitor called crizotinib developed by Pfizer (PF) for non-small-cell lung cancer demonstrated it shrank the tumors in most of the 82 patients after two months of treatment. Knowing in fact that it was too mature to fall for the drug, oncologists, nevertheless, couldn’t stop themselves from wowing crizotinib at the 2010 cancer conference meeting of the American Society of Clinical Oncology. The patients had advanced cancers, including some who had brain metastasis and had been treated with an average of three other drugs to no avail. Pfizer’s ALK inhibitor crizotinib showed no serious side effects. Larger trials were required, however, to confirm the drug’s safety, replicate its efficacy, see whether it would improve survival and whether cancer resistance would emerge in some patients as it usually does following initial drugs’ efficacy

Since the exciting conference meeting of the American Society of Clinical Oncology, some of the patients who have initially responded to crizotinib relapsed. Cancer resistance to this drug became obvious and its cause was identified as multiple mutations in ALK, including L1196M “gatekeeper” mutation.

Yesterday, a small biotech company, Ariad (ARIA), announced findings about its proprietary ALK inhibitor drug AP26113. The difference between AP26113 and crizotinib is that Ariad’s drug inhibits the ALK mutations, hence no cancer resistance to the drug was observed, as was the cae with crizotinib.

Moreover, in preclinical trials, Ariad’s drug AP26113 demonstrated it also inhibits the epidermal growth factor receptor (EGFR) T790M mutant, which is resistant to the currently approved EGFR inhibitors such as Tarceva (erlotinib) and others. Fifty percent of patients’ cancers are resistant to EGFR inhibitors as a result of the emergence of the T790M “gatekeeper” mutation. Second-generation drugs developed by some firms to inhibit EGFR T790M co-inhibited native EGFR, which is not activated, thus, causing adverse events.

Having said that, it is fair to expect that Ariad’s drug AP26113 might be a breakthrough – a large step forward in the treatment of NSCLC and other cancers, including neuroblastomas, sarcomas and lymphomas. Overcoming Lung cancer resistance to therapeutics would translate into 125,000 resistant NSCLC patients globally. Add to this number are 40,000 patients with ALK-positive NSCLC that have no targeted treatments. The other cancers that the drug is expected to be effective in treating further expand the market. Ariad decided to file the IND for AP26113 this month. The small firm is looking forward to moving the drug into a Phase 1/2 clinical trial in the third quarter of this year.

Although these are early results, they are, nevertheless, convincing and very promising. We will be surprised if we do not see deep-pocketed pharmaceutical oncology firms transform their envy into a decision to acquire the genius and its breakthroughs.

Data on the EGFR activity of AP26113 will be presented at the upcoming International Association for the Study of Lung Cancer (IASLC) 14th World Conference on Lung Cancer, to be held July 3 to 7, 2011, in Amsterdam. The mini oral presentation and electronic poster entitled, “AP26113: a potent ALK inhibitor, is also active against EGFR T790M in mouse models of NSCLC,” will be presented on Tuesday, July 5, 2011.

We are long ARIA
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