After reporting a miss in its Phase III trial of Amoxicillin Pulsys in adult patients with strep throat last month, Advancis Pharmaceutical Corp. had hoped the product would yield better results in children.
However, top-line data from its Phase III study in pediatric patients with pharyngitis/tonsillitis due to Group A streptococcal infections showed that the drug failed to demonstrate statistical non-inferiority when compared to penicillin, and that the rate of bacterial eradication was lower than reported in the adult trial.
Those results put Advancis in a position of possibly having to rethink its development strategy, since its version of amoxicillin was the first product created using the company's Pulsys technology, a once-a-day delivery system based on the concept that bacteria are killed more efficiently by antibiotics released in front-loaded staccato bursts.
"As of right now, we'll be looking at continuing the development of Amoxicillin Pulsys, unless further data analysis" suggests otherwise, said Bob Bannon, director of investor relations for the Germantown, Md.-based company. He added that Advancis planned to release further details when reporting its second-quarter earnings Aug. 4.
"We'll be in a better position to talk about our future strategy then," Bannon said.
The pediatric trial evaluated a once-daily "sprinkle" formulation of Amoxicillin Pulsys for seven days at two dosage levels - 475 mg for patients between 6 months and 4 years old, and 775 mg for patients between the ages of 5 and 12 - vs. an oral suspension of 10 mg per kilogram of penicillin VK dosed four times per day for 10 days. Throat cultures taken at the end of the treatment period showed bacterial eradication of 65.3 percent (132/202) for patients receiving Amoxicillin Pulsys, compared to 68 percent (132/194) of those receiving penicillin.
Shares of Advancis (NASDAQ:AVNC) fell 30 cents Friday, or 17.1 percent, to close at $1.45.
It is the second major drop this summer in the company's stock, which was valued at just less than $5 per share before Advancis reported missed endpoints in the adult study in mid-June. Results of that Phase III trial, evaluating 775-mg Amoxicillin Pulsys tablets administered to adult patients for seven days, fell short of the 85 percent bacterial eradication benchmark set by the FDA, and also failed to show statistical non-inferiority to a 10-day treatment of 25 mg of penicillin given four times per day. Of the patients receiving Amoxicillin Pulsys, 76.6 percent showed bacterial eradication vs. 88.5 percent in the penicillin arm. Following the news, Advancis' shares lost nearly 60 percent, closing at $2.03. (See BioWorld Today, June 16, 2005.)
Despite the disappointing results from the adult patient population, the company had expected better data from the children's trial, Bannon said, since the Amoxicillin Pulsys product would be delivering more drug per pound to each patient. Also, the sprinkle formulation - designed as tasteless granules that can be sprinkled on tablespoons of food such as pudding, yogurt or ice cream - seemed certain to ensure greater dosage accuracy and compliance compared to an oral suspension.
"All that gave us some confidence going into this trial," he told BioWorld Today. "But, still, we ended up significantly below where we were in the adult trial and far below the 85 percent eradication we need to reach."
Bannon said further analysis is expected to determine whether additional studies of Amoxicillin Pulsys would be worthwhile. The company might look at increasing the treatment period from seven to 10 weeks in adult patients, and, for a pediatric trial, might consider differing dosing levels or narrowed patient populations, he said.
Advancis is developing Amoxicillin Pulsys with New York-based Par Pharmaceutical Companies Inc., according to a joint marketing agreement that includes a 50-50 split of any profits.
"That's still in place right now," Bannon said, though he added discussion between the companies likely will take place over the next few weeks.
Advancis' amoxicillin was the only Pulsys-based product in the clinic, though the company has other antibiotics in preclinical development, including a Pulsys version of Augmentin, a combination of amoxicillin and potassium clavulanate. Plans also include the creation of a Pulsys formulation for the antibiotic Keflex, which Advancis acquired from Indianapolis-based Eli Lilly and Co.
"That is certainly something that is still on the table," Bannon said of the Keflex Pulsys product.
In the meantime, the company might be able to leverage Keflex, which recorded sales of $1 million during the first quarter.
"That's one bit of good news," Bannon said. "As well as the Keflex asset, the company has about $40 million in cash. That should allow us a number of alternatives."