With FDA Nod, Agios, Celgene Get Speedy OK For Blood Cancer Drug

Xconomy Boston — 

[Updated, 2:10 pm ET, see below] The FDA approved a new blood cancer drug today. Called enasidenib (Idhifa), it’s the latest therapy sold by Celgene, the big cancer drugmaker from Summit, NJ. But the news is significant for other reasons.

The drug is the first product to come from the labs of Agios Pharmaceuticals (NASDAQ: AGIO). The Cambridge, MA, firm began as a startup in 2008, seeded by Arch Venture Partners and Flagship Ventures, and was later backed by Third Rock Ventures and others. Agios went public in 2013 and has now made the transition to an independent, commercial-stage company. Agios and Celgene (NASDAQ: CELG) share rights to enasidenib as part of a wide-ranging alliance that began in 2010 and remains intact. Agios will share in the drug’s profits in the U.S., and get royalties on any revenue generated on sales worldwide. Celgene has the rest of the drug’s rights.

[Updated with pricing information] The drug has a list price of $24,872 per month, according to Celgene spokesman Greg Geissman. In clinical testing, patients spent a median of 4.3 months on drug, according to Geissman. In practice that would translate to about $106,950 per patient, per course, before discounts Celgene negotiates with insurers and their agents. But Geissman says Celgene is working with payers on “patient-centric agreements” so eligible patients can get immediate access to the drug with “no out-of-pocket costs…other than those covered by federal healthcare programs.”

The FDA has approved enasidenib for patients with acute myeloid leukemia (AML)—a progressive, deadly cancer of the blood and bone marrow—who haven’t responded to current treatments and have a mutation to an enzyme called IDH2. When IDH2 is mutated in cancer, it creates a byproduct that flips a genetic switch in immature bone marrow cells. Those cells then don’t develop properly, and start multiplying wildly, rather than maturing into the blood cells they were supposed to become.

By binding to the mutated enzyme, enasidenib is supposed to block the byproduct and allow bone marrow cells to mature normally. As such, the drug works very differently than chemotherapy, which kills cancer and healthy cells alike. Celgene estimates that 8 to 19 percent of AML patients–some 1,200 and 1,500 in the U.S. alone—have an IDH2 mutation. There are roughly 21,000 new cases of AML every year. A majority of patients with the disease relapse.

There are still questions to answer about enasidenib’s safety in the long term, effectiveness, and durability—a longer, larger Phase 3 trial is underway, and should provide clearer answers. The drug was approved based on early clinical studies of about 200 AML patients, showing that after at least six months of treatment with enasidenib, 19 percent of patients had no trace of disease—what’s known as a complete response—for a median of 8.2 months. Some 34 percent of the 157 patients who needed blood transfusions because of their disease at the start of the trial no longer needed them after treatment with the Agios drug.

However, the drug was given a warning on its FDA label for a potentially fatal condition called “differentiation syndrome,” characterized by a dangerously high fever, fluid around the lungs or heart, and other problems. The condition, which can be fatal if not treated with steroids, affected 14 percent of patients on enasidenib. Nausea, vomiting, diarrhea, decreased appetite, and elevated bilirubin levels were also associated with treatment.

Enasidenib put Agios on one of the quicker development paths for a cancer drug in recent memory. It discovered the drug in 2009, filed papers with the FDA (a so-called investigational new drug application, or IND) to begin its first trial of the drug in June 2013, and dosed the first patient two months later. Today’s approval marks a roughly four-year timeline from IND to market, and eight years from discovery.

By comparison, it typically takes about eight years for a cancer drug to go from the start of its first trial to approval, and an average six years of development before that, according to the American Cancer Society. Some notable exceptions include Novartis’s imatinib (Gleevec), Pfizer’s crizotinib (Xalkori), and Millennium Pharmaceuticals’s bortezomib (Velcade).

Agios has two particularly critical drugs in development behind enasidenib, each of which could play a much larger role in determining its financial future. The company has full rights to a second AML drug, ivosidenib, for patients with IDH1 mutations, and expects to file for FDA approval by the end of the year. It also holds full rights to a drug called AG-348 for a type of anemia.

For Celgene, meanwhile, the drug’s approval is a measure of validation for the nimble, aggressive partnership strategy the company has carried out over the years. Through a variety of creative deals, Celgene has aligned itself with a number of biotech startups in their early days—among them Agios, Bluebird Bio (NASDAQ: BLUE), and Acceleron Pharma (NASDAQ: XLRN). Experimental Bluebird and Acceleron medicines for multiple myeloma and beta-thalassemia are progressing forward in clinical testing.

Here’s more on Agios and CEO David Schenkein (pictured), a former top Genentech executive who left the company to run the young startup in 2009.