Enrollment is now open in two clinical trials of XOMA Corp.'s gevokizumab for inflammatory diseases. One trial, a Phase III study, will evaluate gevokizumab for noninfectious uveitis, while a Phase II trial will look at gevokizumab for erosive osteoarthritis of the hand.

Investors greeted XOMA's progress to late-stage studies by giving the company's stock (NASDAQ:XOMA) a healthy bump. It gained 26 cents, or 9.4 percent, to close Wednesday at $3.03.

"There are patients actively being screened," Paul Rubin, XOMA's chief medical officer, told BioWorld Today. For erosive osteoarthritis, Rubin said, "we hope we can finish enrollment by the end of the year."

For noninfectious uveitis, the goal is to have top-line data by the end of 2013.

The noninfectious uveitis study will enroll patients with active, noninfectious, intermediate, posterior, or pan-uveitis with a vitreous haze score equal to or greater than 2+ on the National Eye Institute's Standardization of Uveitis Nomenclature scale in at least one eye. Subjects will be randomized to receive one of two doses of gevokizumab or placebo.

The primary endpoint of the study is proportion of patients demonstrating a significant reduction in vitreous haze score on day 56. Additional endpoints include response rates at other time points and changes from baseline in visual acuity.

XOMA reported positive data from a Phase II pilot study in Behcet's uveitis in June 2010, with all seven Behcet's uveitis patients reporting rapid reduction of intraocular inflammation and improvement in visual acuity on gevokizumab treatment.

"Patients rarely have a spontaneous or placebo response," Rubin said. "In our trial, all seven responded as early as four days after therapy, and all had significant response within two weeks of treatment."

Those strong, early results gave XOMA confidence to go forward with its larger Phase III trial in noninfectious uveitis.

XOMA also is enrolling for a Phase II proof-of-concept study in erosive osteoarthritis of the hand. That study will enroll about 90 patients, randomized to gevokizumab or placebo, with the goal of tracking a significant improvement from baseline in the mean Australian/Canadian Hand Osteoarthritis Index (AUSCAN) pain score at three months. Additional endpoints will include pain, stiffness, function, radiographic changes, changes in C-reactive protein and concomitant acetaminophen use.

Gevokizumab is different from a standard monoclonal antibody in that it allosterically modulates its target, interleukin-1-beta, "rather than binding to the business end of the molecule," Rubin said. Allosteric binding alters the signal sent by IL-1-beta, which has been shown to be involved in a number of auto-inflammatory diseases.

Les Laboratoires Servier paid $15 million up front and made a $19.9 million loan to XOMA for certain rights to gevokizumab in diabetes, cardiovascular disease and Behcet's uveitis, with milestone payments that ranged from $470 million to $800 million, as well as a significant investment in development expenses. (See BioWorld Today, Jan. 5, 2011 .)

That agreement called for XOMA and Servier to jointly develop and commercialize gevokizumab (also known as XOMA 052).

XOMA retains commercial rights and options in the U.S. and Japan for Behcet's uveitis and other inflammatory and oncology indications. Servier has worldwide rights to gevokizumab for diabetes and cardiovascular disease indications, and rights outside the U.S. and Japan for other indications.

Servier would pay for the first $50 million of development expenses for Behcet's uveitis and 50 percent of further development expenses, and would fund development for cardiovascular disease and diabetes. XOMA takes responsibility for manufacturing gevokizumab through clinical development and launch and expects to continue manufacturing the drug over the long term.

XOMA has received $35 million in cash payments and loans from Servier, and it was eligible for another $470 million in milestone payments and tiered royalties up to the midteens.

IL-1 is a target that has generated a great deal of interest, but few viable candidates. Thousand Oaks, Calif.-based Amgen Inc. has an IL-1 blocker, Kineret, for rheumatoid arthritis, but it has not been very successful on the market.

And Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc.'s IL-1 blocker Arcalyst (rilonacept) is approved for cyropyrin-associated periodic syndromes (CAPS), but earned net sales of only $25.3 million 2010. In a recent Phase III trial in gout, Arcalyst met all of its endpoints. (See BioWorld Insight, Jan. 10, 2010.)

Novartis AG, of Basel, Switzerland, also has an IL-1 inhibitor, Ilaris (canakinumab), that is approved for CAPS and may present competition in other IL-1 indications.

Rubin said XOMA expects gevokizumab to have an advantage over those and similar competitors because of its more convenient once-monthly, subcutaneous dosing form.

Simos Simeonidis, an analyst with Cowen and Co., wrote, "The obvious bear story and biggest risk for investors in XOMA, in our view, is that the company has moved into two pivotal Phase III trials in NIU and BU on the basis of a very small, albeit very impressive, set of data from a pilot study in just seven BU patients." That trial was carried out in Turkey, Simeonidis noted, a location investors tend to be uneasy with in terms of clinical trial experience.

XOMA raised $39.2 million in March to fund its Phase III program and three proof-of-concept trials, and as a result its stock has gained steadily. "We see room for more upside potential in XOMA shares," Simeonidis wrote. (See BioWorld Today, March 7, 2012.)