Yesterday Cambridge, MA-based Ariad Pharmaceuticals (NASDAQ: ARIA) began dosing patients in a trial of its third cancer drug, which the company believes may pack a double punch against the disease. The medicine, AP26113, inhibits two genetic targets found in some patients with solid tumors, particularly non-small cell lung cancer. The initial phase of the trial will include 30 to 50 patients, and is designed to help the company define the proper dose and measure tolerability. Ariad expects to begin the second phase of the trial in 2012.
AP26113 blocks overactive expression of both anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR), two of the hottest targets in oncology drug development. Pfizer’s recently approved crizotinib (Xalkori) targets ALK, while Genetech’s hit drug erlotinib (Tarceva) inhibits EGFR. Ariad’s CEO Harvey Berger believes his company has a chance to come in with a best-in-class competitor. “It’s really two drugs in one,” he says of AP26113.
Ariad’s scientists designed the drug to inhibit not just ALK and EGFR, but also mutations of those genes that cause patients to become resistant to other targeted drugs. For example, Ariad’s drug may help patients who stop responding to crizotinib because they have a mutation that, in essence, shields their tumor from the drug. “Crizotinib is a breakthrough drug,” Berger says. “But it has incredible limitations. Every patient eventually fails. We believe one of the major reasons for that progression is the development of resistant mutants.”
In the second phase of the trial, Ariad plans to test the drug in lung cancer patients whose tumors are positive for ALK or EGFR and who have shown resistance to at least one marketed drug that targets those factors. The trial will also include patients with ALK-positive cancers who have not yet taken other drugs in that class, as well as patients with other solid tumors that are known to express ALK. Genetic testing, therefore, will be an essential component of the development plan for AP26113.
The progress of AP26113 is only adding to investor excitement over Ariad’s recent achievements. In May, Ariad and Merck (NYSE: MRK) presented positive results from a late-stage trial of ridaforolimus, a drug the two companies are developing together to treat sarcomas, at the American Society of Clinical Oncology meeting. Merck filed for FDA approval for the drug in August. Ariad is also completing pivotal trials of ponatinib, which it developed to treat two forms of leukemia. If all goes well, both drugs could be approved by the end of next year. Ariad’s stock has doubled since the beginning of the year, to nearly $10 a share.
The Merck collaboration on ridaforolimus has provided Ariad with the resources it needs to go solo on its next two products, Berger says. Merck is covering marketing and development costs, and has agreed to pay Ariad tiered, double-digit royalties on sales of the product. The two companies will co-promote the drug, which will give Ariad a chance to build up a salesforce—and name recognition among oncologists—before it starts hitting the pavement to promote ponatinib and AP26113, Berger says. “When it was very early in the company’s evolution, we felt it made sense to partner,” he says. “But once we build a commercial organization and have the expertise to run global trials, it’s clear we can do it ourselves. We want to build a major cancer business and really make a difference for patients of many different types.”