Login to Your Account

So long, Sollpura: Anthera sacks lead program after dismal 'RESULT'


By Marie Powers
News Editor

Anthera Pharmaceuticals Inc. reported disastrous results from phase III RESULT study of Sollpura (liprotamase), which failed to reach the noninferiority margin of the coefficient of fat absorption (CFA) primary endpoint in individuals with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). Sollpura did achieve the secondary endpoint of coefficient of nitrogen absorption (CNA), which measures protein absorption. But the findings from RESULT – following a miss in the earlier phase III SOLUTION trial in CF patients with EPI – prompted Anthera to suspend development of the recombinant pancreatic enzyme replacement therapy (PERT), halting the 20-week extension period of RESULT, the SIMPLICITY study in children 28 days to <7 years of age assessing Sollpura powder for oral solution and the long-term safety EASY study.

The program's termination left Anthera, of Hayward, Calif., on life support. Shares (NASDAQ:ANTH) fell Monday to an all-time low of 40 cents as the company acknowledged that it was evaluating "all strategic alternatives." The stock closed at 50 cents, a decline of $2.14, or 81 percent. Nearly 39.6 million shares were exchanged, or about 24 times the stock's average daily volume.

In a five-minute conference call in which the company took no questions from analysts, Craig Thompson, president and CEO, essentially recited details from an issued statement. RESULT's design, he explained, was based on the outcome of the phase III SOLUTION study and included a higher starting dose and more aggressive dose optimization based on clinical signs and symptoms of malabsorption.

Findings from SOLUTION, reported in December 2016, showed a narrow top-line miss. After a three-week run-in period on Creon or Zenpep (pancrelipase, Allergan plc) to establish baseline CFA, 126 patients enrolled in SOLUTION were randomized to Sollpura or Pancreaze (pancrelipase, Janssen Pharmaceuticals Inc.), with the primary endpoint set at noninferior CFA measured after eight weeks. The main mark was margin in the primary modified intent-to-treat (mITT) analysis, which fell just short. Researchers did find that, by additional pre-specified analyses of CFA (mITT-baseline observation carried forward and per protocol), Sollpura hit the noninferiority goal. The study also confirmed that the ratio of the three enzymes in Sollpura turned up appropriate response in the CNA. (See BioWorld Today, Dec. 29, 2016.)

In the randomized, open-label, assessor-blind, noninferiority, active-comparator RESULT study, which enrolled 140 patients, those randomized to Sollpura received a starting dose that was approximately 25 percent higher than their pre-study porcine PERT dose, and 59 percent received additional dose adjustments designed to simulate "real-life" conditions, yielding a mean Sollpura dose of 8,673 (range 2,925-14,941) lipase units/kg/day, which was substantially higher than the comparator Pancreaze mean dose of 6,527 (range 2,358-10,253) units/kg/day and higher than the mean Sollpura dose of 7,286 (range 4,478-10,000) units/kg/day in SOLUTION.

"Although a proportion of patients randomized to Sollpura maintained or improved their CFA from baseline, a higher proportion of patients [in RESULT] experienced a worsening," Thompson said. The mean treatment difference in CFA change from baseline was 14.3 percent, with upper and lower 95 percent confidence intervals of -18.22 and -10.39.

The treatment difference in CNA change from baseline (-1.53 percent) was within the 15 percent noninferiority margin. In comparison to the earlier SOLUTION study, the presence or absence of concomitant gastric acid suppressants had no meaningful effect on CFA (mean changes from baseline in CFA of -15.06 percent and -16.58 percent, respectively).

RESULT also was modified from SOLUTION to provide a shorter treatment duration of four weeks, with three weeks of dose optimization and one week of stable dosing. The trial design was discussed with FDA officials prior to administration and was approved by the Cystic Fibrosis Foundation Therapeutics Development Network (CFFTDN) protocol review committee and the European Cystic Fibrosis Society Clinical Trial Network executive committee, according to Anthera.

In December 2017 and again in January, prespecified interim futility analyses were conducted by a data monitoring committee comprising experts appointed by the CFFTDN when approximately 25 percent and 50 percent of patients, respectively, completed the four-week treatment period. In both instances, the committee recommended the study continue to completion.

'There may be some interest' in assets

With Sollpura at the end of the road, Anthera has its back to the wall. Its other asset, blisibimod, fell short in the phase III CHABLIS-SC1 study testing the selective peptibody antagonist of the B-cell activating factor cytokine against systemic lupus erythematosus, or SLE. (See BioWorld Today, Nov. 11, 2016.)

Although prospects initially looked brighter for blisibimod in the phase II/III BRIGHT-SC study in individuals with IgA nephropathy, slow recruitment forced the company to convert BRIGHT-SC to a phase II study. In August 2017, Anthera reported positive top-line data and said it planned to meet with the FDA to discuss a phase III program, but those trials never began, according to Cortellis Clinical Trials Intelligence. (See BioWorld Today, Dec. 8, 2016.)

Piper Jaffray's Edward Tenthoff voiced surprise at the RESULT findings, given the protocol amendment, as he downgraded Anthera's shares to "underweight" from "overweight" and lopped the price target to 10 cents from $4.

Likewise, Jefferies Group LLC analyst Matthew Andrews offered scant encouragement. Although, based on positive phase II blisibimod data in IgA nephropathy and intellectual property, manufacturing and CMC know-how for Sollpura, "there may be some interest from pharma/biotech in these assets," he wrote, Andrews nevertheless knocked the stock's price target down to 50 cents from $2 based on the risks of raising additional capital and remaining a "going concern."

Anthera finished 2017 with cash and equivalents of $2.2 million. In January, the second closing of a PIPE transaction generated net proceeds of $11.1 million. During the first quarter, the company also received $3.1 million from the exercise of warrants and sale of shares in relation to an equity purchase agreement.