Wednesday, December 22, 2010

Federal grants boost several Mass. diabetes-focused companies

By Julie M. Donnelly

Massachusetts life sciences companies took home the second largest chunk of federal funds that were part of the Qualifying Therapeutic Discovery grant program, a total of $126 million distributed among 300 different companies. The list of projects that were awarded the stimulus-funded research and development grants tells a story about what therapeutic areas are top-of-mind for health officials. While cancer was, by far, the top-earning indication, the government also took notice of a significant number of companies working on potential therapies for diabetes or its complications.

It’s not hard to see why: A recent study by insurer UnitedHealth projected that the cost of the disease would hit $3.5 trillion, yes trillion, by 2020. The U.S. Centers for Disease Control reports that it is the second most expensive disease for the healthcare system, after cancer, and the number of Americans with diabetes is growing rapidly.

Enter new technology. One of the most devastating complications of diabetes is nephropathy — a type of chronic kidney disease that is specific to Type 2 diabetics. Lexington-based Concert Pharmaceuticals Inc. is getting ready to enter the clinic with a drug candidate called CTP499, which is designed to combat the nephropathy complication and stave off dialysis and the need for kidney transplants.

“What makes it interesting is that there is a substantial medical need and only one class of drugs on the market,” Concert CEO Roger Tung said. The current treatments are either ACE or ARB inhibitors that target the same pathway to lower blood pressure, which also has an anti-inflammatory effect on the kidneys. But these are drugs that are marketed for high blood pressure, and are used off-label for chronic kidney disease. The Concert drug candidate primarily addresses the underlying inflammation and also acts against fibrosis, or scarring of the kidneys. Tung said the mechanism is both distinct and additive to current therapies, and might be used as a mono-therapy or in conjunction with other drugs. The oral therapy, which netted $244,000 through the Qualifying Therapeutic Discovery grant would be taken once or twice a day.

Another potential drug that was recognized by the federal grant program — established by the health reform act earlier this year — addresses the inflammation at the root of diabetes itself. Catabasis Pharmaceuticals Inc., based in Cambridge, is a relatively new player that landed a whopping $40 million Series A venture round in April. The company’s lead drug candidate, part of its so-called CAT-1000 series of compounds, also netted $244,000 from the federal program. The novel small molecule drug, which would also be an oral therapy, would not just treat blood glucose levels like other drugs on the market, but is designed to have a disease-modifying effect, according to Catabasis CEO Jill Milne. She said the drug may also serve to combat inflammatory complications like the aforementioned nephropathy and retinopathy.

“This is such a difficult disease to treat because until complications begin to affect the patient, they don’t notice, so the disease often isn’t caught early,” Milne said. She said the company is doing preliminary work to see if the drug candidate might also be a potential therapy for type 1 diabetes, and hopes that some day the company’s drug could be used to catch pre-diabetes and treat patients before the disease becomes full-blown.

Both Tung and Milne said that the federal funds are helping to accelerate drug development. Milne said Catabasis is in hiring mode, seeking to expand from its lean staff of 12. She also said the funds helped to enable the company to purchase a second mass spectrometer, a key tool used in drug discovery, which cost about $200,000. The goal of the program is to drive more compounds toward expensive later stage trials and finally to market.

One local company that could see a diabetes complication treatment approved by the U.S. Food and Drug Administration is Watertown-based pSivida Corp. The 23-person company has an FDA decision date of Dec. 30 for its drug-device combination product to treat the eye condition Diabetic Macular Edema, which is licensed to Georgia-based Alimera Sciences Inc. The potential therapy, called Illuvien, uses a needle to deliver an inserter device, smaller than a grain of rice, that delivers a continuous low dose corticosteroid drug to the back of the eye, for three years. While pSivida has two out-licensed drugs on the market, Lori Freedman, vice president of corporate affairs at pSivida, said those are for smaller markets. Illuvien is the big kahuna.

“There are one million cases of DME in the U.S. and the market is estimated at between $1.5 billion and $4 billion per year,” Freedman said. The current treatment for DME is a laser, not a drug, but it has limited efficacy. PSivida’s late-stage trials focused on patients for whom laser treatment had failed.

PSivida’s FDA decision date comes at a time when there is increased scrutiny of diabetes treatments, both due to safety and efficacy concerns. Milne said that while the pendulum may have shifted too far toward risk-aversion at the FDA, a high level of rigor regarding applications is warranted.

“We have to figure out how to address risks, particularly cardiovascular risks, because these are patients who already have  high incidence of cardiovascular disease,” Milne said. She said early stage companies like hers can incorporate new FDA guidelines on diabetes drugs that were implemented in the past few years, while later-stage drug compounds may have a tougher time complying with added regulatory oversight.

 “Another reason the bar is so high is that there are a lot of drugs already available and a new drug must be better,” Tung said. But he said that when it comes to chronic kidney failure many patients fail on other drugs, and still end up with end-stage renal failure, meaning that there is a significant unmet medical need for a drug to treat those patients. Tung said he also has a personal stake that fuels his drive to get a new diabetes drug to market. His father was a diabetic and passed away last summer due to a heart attack. He also had low kidney function.

“Unfortunately we all know someone with diabetes these days,” Tung said.