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Alvine and Dandy: Option Deal Brings $70M AbbVie Up Front

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By Randy Osborne
Staff Writer

AbbVie Inc.'s $70 million up front buys an option to acquire Alvine Pharmaceuticals Inc.'s drug candidate for celiac disease or the company itself, after Phase IIb trials are finished with ALV003, a two-enzyme combo that degrades gluten.

The 500-patient Phase IIb study with ALV003, which is composed of a cysteine protease and a prolyl endopeptidase, should be finished late next year or early in 2015, said James Watson, chief business officer of San Carlos, Calif.-based Alvine.

"It's starting very shortly, the next couple of months or so," Watson said. Patients will be followed for three months in what Watson called the "landmark" study, which comes on the heels of the only successful Phase IIa study ever done in that indication. Data were reported at the Digestive Disease Week meeting last year.

"The primary endpoint for the [Phase IIb] study will be the biopsy-based measure of intestinal inflammation," Watson said. "That's also the way this disease gets diagnosed," and was the endpoint of the Phase IIa experiment.

Alvine also has a patient-reported outcome tool "that's not been done before," though similar measures have been used in such conditions as reflux disease, Watson said. "This is, hopefully, a turning point [in celiac therapy]," he told BioWorld Today. "We have a big partner behind it, and the capital necessary to do the trial the right way. The chances of a therapy getting to market have really gone up."

Celiac disease, an acquired autoimmune disorder that hits genetically susceptible people after they get gluten in their diets, afflicts about 6 million people in the U.S. and Europe.

"The prevalence is pretty widely documented, about 1 percent of the population, so you've got 3 million people walking around in the U.S. alone," Watson said. "Once you have it, you have it for life. The only approach is going on a gluten-free diet, and good luck, so to speak."

Patients "can obviously reduce their intake by focusing on [avoiding foods with gluten], but it's virtually impossible to get to zero," Watson said. "Gluten is in all kinds of things – soy sauce, food colorings – numerous things that aren't even labeled. You wouldn't have any way of knowing."

Patients suffer ongoing intestinal inflammation, which leads to poor absorption of nutrients and other conditions brought about by the low-gluten diet.

About 60 percent of patients will develop osteoporosis, and 40 percent will get anemia, upping their chances of chronic kidney disease, malignancies and "all kinds of other complications," Watson said.

ALV003, which has fast-track status from the FDA, targets "a big chronic specialty market, mainly treated by gastroenterologists," he said. Chicago-based AbbVie "has been with us for some years," Watson said. "They were an investor in our Series A extension."

Farther back in its pipeline, Alvine has a discovery-phase program investigating transglutaminase 2 (TG2), a multifunctional protein with enzymatic, cell signaling and cell adhesion activities, which might be useful in celiac disease as well as neurological disorders such as Huntington's disease, as well as Type II diabetes, liver cirrhosis and fibrosis, renal scarring, vascular remodeling and several cancers.

There's also early research into HLA-DQ2 blockers. HLA-DQ2 is a Class II heterodimer of human leukocyte antigen, and is found in 30 percent to 40 percent of the population, and represents what Alvine calls "a necessary but not sufficient requirement" for celiac disease to arise. In celiac disease patients, the antigen presenting cells bind to gluten peptide fragments via the HLA-DQ2 (or –DQ8 binding groove) which causes T-cell stimulation and a local and system immune response.

Others working in the HLA-DQ2 space and celiac disease include ImmusanT Inc., of Cambridge, Mass., which reported in the fall of 2012 that X-ray crystallography let scientists visually determine how T cells interact with gluten that causes celiac disease in patients with the DQ8 susceptibility gene, providing insight into how celiac disease pathology is triggered.

ImmusanT is developing a blood test and therapeutic vaccine, Nexvax2, for patients with celiac disease who carry HLA-DQ2.

New Alvine partner AbbVie split from Abbott at the start of the year, taking several dozen marketed products and a portfolio of late-stage compounds in immunology, neuroscience and oncology, leaving Abbott to focus on diagnostics, medical devices, nutritionals and branded generic pharmaceuticals. (See BioWorld Today, Jan. 3, 2013.)

The main focus of the spun-out firm is Humira (adalimumab), approved for a handful of indications, including gastrointestinal disorders such as Crohn's disease and ulcerative colitis, so ALV003 lands right in the sweet spot.

"Overall, it's a good fit," Watson said. "We expect AbbVie to treat this as the high priority it deserves."