A shipping glitch that might have chilled to near freezing study packages of Ampio Pharmaceuticals Inc.'s late-stage osteoarthritis of the knee (OAK) treatment, Ampion (aspartyl-alanyl diketopiperazine), will delay analysis of data from a pivotal study of the drug, the company said.

News of the mishap sent Ampio shares (NASDAQ:AMPE) tumbling, down 24 percent to a $5.66 close as investors speculated about the implications for the Englewood, Colo.-based company's plans to file a biologics license application (BLA) in the first quarter of 2015.

Ampio said it's working to keep the BLA on track and has already spoken about the issue with the FDA, which agreed to analyze data from the impacted trial, called STEP, in support of its BLA.

Trial supplies of Ampion were housed, packaged and shipped in early January by a specialized drug shipment vendor Ampio didn't identify. The vendor was contractually obligated to maintain pre-determined temperature requirements under all conditions, company CEO Michael Macaluso said.

The first patient dosed with Ampion in the 500-person study received it Jan. 13. But the temperature problem wasn't spotted until Ampio's contract research organization (CRO) conducted a full documentation review following the unblinding of the study, Ampio said. The CRO found multiple instances in which the in-package temperature monitor fell significantly below the 15 degrees Celsius (59 degrees Fahrenheit) minimum required, according to Macaluso. Much of the drug product received at the clinical sites had been below the temperature requirement and may have been frozen for some period of time, he added, an issue that may have damaged its potency.

"Pivotal clinical trial drug specifications dictate precise temperature and handling conditions for all study drug product in order to assure that the conclusions about the safety and effectiveness of the tested drugs will be accurate and repeatable during routine clinical use," Macaluso added.

In addition to trying to salvage the STEP data, Ampio is consulting with its regulatory advisors to determine whether it can submit data from a multiple injection study currently under way to support its BLA. Packaging the multiple-injection study with data from the company's first pivotal trial of Ampion, the single-injection SPRING study, "may provide a more comprehensive and clinically meaningful analysis by the FDA reviewers," the company said.

It's an outcome the company hopes will come to pass, since early results in the open-label portion of the the safety-focused multiple injection study have shown that patient's pain scores, as evaluated by the WOMAC A osteoarthritis pain index, improved by 86 percent from baseline six weeks following the first injection, compared to about 40 percent in the SPRING study at the same time point. Given those results, the company said it thinks it's unlikely that doctors will choose to treat severe chronic pain patients with a single injection.

Reaching patients with severe osteoarthritis could be an important differentiating factor for Ampio, since those patients previously have been excluded from industry-sponsored trials, according to Jefferies analyst Biren Amin.

Whether Ampion's intemperate voyage unearthed an isolated supply chain problem or previously undisclosed vulnerability in the human serum albumin-based therapy is unclear. Ampio officials did not respond to an interview request.

Beyond OAK, Ampio is evaluating Ampion as a potential treatment for Crohn's disease, chronic obstructive pulmonary disease and other chronic inflammatory conditions. It's also evaluating Optina, an orally administered ultra-low dose of danazol, to treat diabetic macular edema.

Ampio raised net proceeds of about $64.4 million on March 5 to give Ampion the final push to potential approval. At June 30, the company had about $65.6 million in cash and equivalents. (See BioWorld Today, March 3, 2014.)