Lexicon Pharmaceuticals, Inc. (LXRX) shares are surging in Tuesday trading after the company announced its oral diabetes drug LX4211 met its primary endpoints in mid-stage clinical trial of Type 2 diabetes patients with stage 3 or stage 4 kidney disease. LX4211 is a first-in-class inhibitor of sodium glucose transporters 1 and 2 (SGLT1 and SGLT2), low-affinity transporters that play a key role in absorption of glucose in the gastrointestinal tract and renal glucose reabsorption.
In the more than 245 million Type 2 diabetes patients worldwide, insulin production is either low or inefficient in regulating blood glucose levels, which can lead to severe complications, including kidney failure, heart disease and stroke. Hemoglobin A1c level, a measure of glucose in the blood over time, is widely considered the “gold standard” in diabetes control.
The primary endpoint of the Lexicon phase 2b trial was reduction in post-prandial (after meal) glucose, a time when diabetes patients generally experience spikes in blood sugar as carbohydrates are converted into glucose and enter the bloodstream. In the 30-patient, proof-of-concept study, the treatment arm was given a 400 mg dose of LX4211 orally once per day before breakfast. A control group was given a placebo on the same schedule.
LX4211 provided clinically meaningful and statistically significant reductions in post-prandial glucose. Importantly, these effects were maintained in a sub-group with the most advanced renal impairment, pre-defined as those with glomerular filtration rate (GFR) less than 45 ml/min/1.73 m2. LX4211 also produced significant elevations in GLP-1, a hormone involved in control of glucose and appetite.
"Our hypothesis was that LX4211 would improve glycemic control even in patients with the greatest degree of renal impairment due to its inhibition of SGLT1 in the GI tract," said Pablo Lapuerta, M.D., Lexicon's chief medical officer. "[The results] support the rationale for demonstrating effective HbA1c reduction in a larger, longer-term Phase 3 trial," added Lapuerta.
No serious adverse events were observed and no patients dropped-out of the study due to adverse events.
A prior phase 2 clinical trial showed LX4211 to improve glycemic control in Type 2 diabetes patients with normal kidney function. In this trial, HbA1c levels were reduced by as much as 1.25 percent, compared to 0.49 percent in the control arm after four weeks of treatment, with half of both LX4211 groups (150 mg and 400 mg doses) showing a reduction in HbA1c to at or below 7 percent, a benchmark point in glycemic control.
Shares of LXRX surged more than 20 percent at the opening bell to as high as $3.18 in Tuesday morning trading. So far in 2013, shares were up about 8 percent through Monday’s close at $2.38.