Obtaining an exclusive license from Takara Bio to use its FLT3 mutation for molecular diagnostics applications, InVivoScribe Technologies becomes the latest company to bet that its product can play a role in pharmacogenomic-based FLT3 inhibitors.
Additionally, the license, which excludes Japan, means that Genzyme, Quest, and LabCorp must now obtain a sublicense from InVivoScribe in order to continue offering their in-house FLT3 analyte-specific reagent prognostic testing, according to Jeffrey Miller, the company’s president and CEO.
Miller told Pharmacogenomics Reporter that his firm has begun negotiating sublicenses with “several interested parties,” but “there are no guarantees that any specific party or parties will be offered a sublicense.” These parties were previously in negotiations with Takara, he said.
The licensing comes two months after Genzyme launched a FLT3 mutation test for acute myeloid leukemia prognosis. That assay could potentially identify responders to FLT3-inhibitors if any win US Food and Drug Administration approval.
But just because companies like InVivoScribe are jockeying for position in the FLT3 diagnostic field does not guarantee there will be a pharmacogenomic future in it when drugs start appearing on the market. There are only a few candidates within several years of finishing clinical trials, and even those will likely not become important monotherapies for AML or other FLT3-based indications. Cephalon and likely several other companies employ FLT3 mutation diagnostics during drug development.
A number of companies are studying FLT3 inhibitors. Cephalon’s drug, CEP-701, is in phase II and was granted orphan drug status by the FDA and the company has another phase II compound, KT555; Novartis has a phase II compound, PKC 412, for AML, refractory anemia with excess of blasts, or RAEB, and chronic myelomonocytic leukemia; Millennium Pharmaceuticals has a phase I compound CT 53518 for AML; Exelixis has a phase II compound XL999 for AML; Johns Hopkins University has a phase II compound, AG1295; and Chiron has a phase I compound, CHIR-258, for AML and multiple myeloma.
Still, InVivoScribe is in the early stages of discussions with “a number” of pharmaceutical companies involved in the clinical areas important to FLT3 inhibitors, Miller told Pharmacogenomics Reporter this week.
“It would be our intention to collaborate with potential pharma [partners] to develop suitable ‘theranostic’ products,” he wrote in an e-mail. He did not disclose a timeline.
FLT3 inhibitors may become useful treatments for acute myeloid leukemia and the myelodysplastic syndromes with RAEB. They may also play a role in treating certain rare cases of acute lymphoblastic leukemia.
Miller estimated the potential global market for all FLT3 mutation diagnostics at $5 million.
Genzyme launched its FLT3 mutation test in May as a prognostic assay for AML. At that time, Celeste Chenet-Monte, a Genzyme spokesperson, said the test will be used as a “predictive marker in therapeutic selection of FLT3 inhibitors” once a FLT3 inhibitor hit the market.
“It would be our intention to collaborate with potential pharma to develop suitable ‘theranostic’ products.”
Genzyme does not intend to file the test for clearance as an in vitro device with the US Food and Drug Administration, but plans to sell it as a CLIA laboratory service, she added. InVivoScribe already sells a research-use-only FLT3 diagnostic, said Miller.
Past clinical trials of FLT3 inhibitors have identified a link between mutation status and response, although there is no clear indication that a diagnostic will be a useful guide for physicians.
The drugs under development have also not proven to be active enough as stand-alone therapies for AML, so they are often tested as co-treatments with chemotherapies, Michael Heinrich, a professor of medicine at Oregon Health and Science University Cancer Institute in Portland, Ore., said in May. Another possibility is that FLT3 inhibitors could be used to dampen the growth-factor independence of cells that might otherwise be susceptible to other drugs, such as histone deacetylase inhibitors, said Miller.
According to a spokesperson for Cephalon, the company is not currently planning to develop a diagnostic of its own for its phase II candidate; in its studies it uses a test similar to that developed by Johns Hopkins University researchers. She said it is premature to speculate whether the company would have to pair its FLT3 inhibitor with a diagnostic to identify responders.
Cephalon hasn't explored what sort of activity CEP701 might have in patients without a FLT3 mutation, Peter Brown, the company's vice president of clinical oncology, told Pharmacogenomics Reporter in May. "Our early research suggests that the drug will be most active in patients who have the mutation," he said. The company has not collaborated with any diagnostic companies for a FLT3 theranostic, he added.
Millennium, Novartis, and Pfizer did not respond to questions for comment before press time.
According to the American Cancer Society, there will be about 11,930 new cases of AML in the United States this year, and the 5-year survival rate of adults under 65 is about 33 percent. Currently available AML treatments are associated with treatment-induced mortality rates as high as 25 percent in poor-risk patients, according to the FDA. If FLT3 inhibitors continue to follow the pharmacogenomic route, and responders can be identified using a mutation test, the drugs are likely to be directed against the worst AML cases.