Inotek Pharmaceuticals has started 2017 with a big setback.
The company’s first big Phase 3 test of an experimental glaucoma drug fell far short this morning, leaving the fate of the drug, known as trabodenoson, unclear.
Lexington, MA-based Inotek (NASDAQ: ITEK) said that trabodenoson failed MATrX-1, the first of three Phase 3 trials in glaucoma patients. The drug didn’t best a placebo at reducing eye pressure in glaucoma patients at each of 12 different time points over the course of 84 days.
Inotek blamed a placebo response that it said was 2 to 3 millimeters of mercury, or mmHg (the typical measurement for eye pressure) higher than it saw in Phase 2 testing.
CEO David Southwell added in a statement that the drug hit its mark on a variety of secondary measures and appeared roughly as safe as a placebo. Inotek enrolled 303 patients, and just four on trabodenoson dropped out due to side effects. There was only “minimal” eye redness related to treatment, a common problem with some other glaucoma drugs, Inotek said. Still, investors weren’t seeing the silver lining. Inotek shares plummeted close to 65 percent, to $2.15 apiece, in pre-market trading Monday.
Southwell said the company will determine the next steps for trabodenoson as a monotherapy once it gets more data from the trial later this quarter. The drug is still being tested in two other trials, one of which combines trabodenoson with another glaucoma drug, latanoprost (Xalatan). The combo trial should report data in the middle of the year.
Inotek is one of several companies trying to come up with a new treatment for glaucoma, a chronic condition in which a buildup of fluid increases pressure in the eye, damaging the optic nerve and potentially causing blindness if left unchecked. Patients with glaucoma are usually prescribed eye drops known as prostaglandin analogues (PGAs), many of which are generic. They can also typically end up on one of several other classes of eye drops, such as beta blockers or adrenergic agonists, that are either used to boost the effects of PGAs or serve as an alternative therapy. All of these drugs work by either slowing down the eye’s rate of fluid production or helping fluid leave the eye.
The problem is, while PGAs such as latanoprost—the most commonly prescribed of the group—help the eye drain itself, they don’t directly target the trabecular meshwork, the eye’s main drainage system, which experts say is responsible for the fluid buildup.
Inotek, like Aerie Pharmaceuticals (NASDAQ: AERI), is one of the companies trying to bring a new type of drug into the equation. Its trabodenoson is supposed to spur enzymes within the tissue to clear out the proteins that are clogging up the eye’s drainage system. Inotek is testing trabodenoson in three separate trials—MATrX-1 through 3—and today’s study is the first to produce data so far. (Aerie recently filed for approval of its own treatment.)
Today’s result is a crushing setback for Inotek, particularly since the FDA last year allowed the company to compare its drug to a placebo, rather than the decades old glaucoma drug timolol, in Phase 3 testing. Trabodenoson had had trouble separating from timolol in Phase 2 trials, but going head to head against a placebo instead theoretically lowered its risk of failure.
On average, the highest of three tested doses of trabodenoson outperformed a placebo, but not at every time point, which is why the trial failed. The numbers reported today by Inotek: Patients on the high dose of trabodenoson saw their eye pressure reduced by about 4.25 mmHg, on average, after three months of treatment, compared to 2.38 mmHg for those on placebo. A third trial arm of patients on timolol performed better—their eye pressure was lowered by 5.29 mmHg over three months. Inotek didn’t disclose the results for the two lower doses of trabodenoson.
Inotek will hold a conference call this morning to discuss the news.