Ampio AWOL With Knee-Pain Drug Data Disclosures

Ampio Pharmaceuticals ( AMPE) has touted the pain-relief efficacy of its osteoarthritis drug Ampion in three press releases since August but is so far refusing to provide clinical data sufficient to support its claims.

The Ampion data is missing from Ampio's "Spring" study, which compared two doses of Ampion to matching placebo in 329 patients with osteoarthritis of the knee. The knee of each patient in the study was injected once with either Ampion or saline. The study's primary endpoint was reduction in knee pain at 12 weeks compared to baseline.

Knee pain was assessed using the WOMAC A scale, which awards 0 points for no pain up to 4 points for extreme pain based on patient reporting.

Ampio needs two positive phase III studies in order to seek FDA approval of Ampion for osteoarthritis of the knee. The company is counting the "Spring" study as the first positive study. Ampio met with the FDA last month to discuss the "Spring" study results and requirements for a second phase III study of Ampion. The company hasn't commented publicly on the outcome of the FDA meeting but has previously guided to beginning the confirmatory Ampion study before the end of the year.

Investors who wish to evaluate Ampion's safety and efficacy are out of luck because Ampio had so far refused to disclose publicly relevant "Spring" study data, despite issuing three press releases touting positive results.

"As part of our market development plan for Ampion, we are planning to release all of the data, including important sub-population analyses and 20 week data in upcoming journals, medical conference presentations, and the public via press releases," said Ampio spokesman Rick Giles.

On Aug. 14, Ampio issued a press release announcing the Ampion study achieved its primary endpoint reduction in knee pain with "high statistical significance." Both the 4 ml and 10 ml doses of Ampion provided osteoarthritis patients with pain relief but there was no "significant difference" between the efficacy of the two Ampion doses, the company said.

Here are the Ampion results Ampio chose to include in its announcement:

Patients receiving Ampion achieved a significantly greater reduction in pain (WOMAC A) from baseline to 12 weeks compared to saline vehicle control (p=0.0038).

Patients receiving Ampion experienced, on average, a greater than 40% reduction in pain from baseline.

Ampio failed to disclose any numerical data on pain reduction for patients treated with Ampion. Claiming Ampion patients experienced a 40% reduction in knee pain means little if the company doesn't tell us how much pain they were experiencing at the start of the trial.

Think of it this way: If I offered you 40% of the contents of a sealed safe deposit box in exchange for $100, you'd want to know if the box contained $1 or $1 million before accepting the offer.

The "Spring" study was designed to compare Ampion to saline, so did these placebo patients experience pain reduction, too? The company tells us nothing specific about the placebo patients.

Ampio disclosed a bit more data from the "Spring" study on Sept. 30:

This study demonstrated that a single intra-articular (IA) injection of Ampion resulted in a clinically and statistically significant reduction in pain, with an estimated difference from control at the study endpoint of -0.25 on the WOMAC A scale (95% CI: -0.41 to -0.08, p=0.004), corresponding to a 42.3% improvement in pain at 12 weeks in patients treated with Ampion.

Note: In contrast, despite recommendations against their use, Hylan G-F 20 is the current treatment of choice in patients who cannot be managed with analgesics. In the pivotal trial of a single IA injection of 6 ml Hylan G-F 20, a borderline statistically significant reduction in pain was demonstrated, with an estimated difference from control of -0.15 (95% CI: -0.30 to -0.002, p=0.047), corresponding to a 31.3% improvement in pain over 26 weeks in patients treated with Hylan G-F 20.

Here, Ampio is looking across two different clinical trials to claim Ampion is superior to Hylan G-F 20, an approved osteoarthritis injection sold by the Genzyme unit of Sanofi ( SNY) under the brand name Synvisc. But again, Ampio doesn't provide the data from its own study to back up the superiority claim.

The 0.25 difference on the WOMAC A scale favoring Ampion over placebo is an incremental nugget of data, but Ampio doesn't disclose baseline or post-treatment changes in pain scores for Ampion and placebo patients, respectively. The company clearly has these data, so why not disclose?

This is what the WOMAC A pain score data look like from the Snyvisc label approved by the FDA. These data come from the pivotal phase III study conducted by Genzyme:

Ampio is correct when it says the difference in pain scores between Synvisc and saline control was 0.15. But based on the data above, Ampio's claim that Synvisc demonstrated a 31.3% percent improvement in pain can't be reconciled. I don't know how Ampio calculates the 31.3% improvement, which makes me question the company's claim of a 42.3% improvement for Ampion, particularly since no data to back up its math is disclosed.

Comparing Ampion to Synvisc across two different studies is problematic, made more challenging since Ampio hasn't told us enough about the baseline characteristics of the knee osteoarthritis patients enrolled in the "Spring" study.

Here are the baseline demographics and characteristics of the patients enrolled in Genzyme's Synvisc study. Ampio should provide investors with a similar chart from its study, but has not done so.

Ampio's most recent pronouncement about results from the Ampion "Spring" study was issued on Nov. 4. The press release, which quotes Chief Regulatory Officer Vaughn Clift, dealt mainly with an 8-week extension of the original 12-week study.

Clift:

In the 329-patient Spring study, both the efficacy and safety of the 4 ml and 10 ml doses were equivalent. Both doses were independently statistically significant, therefore Ampio selected 4 ml as the optimal dose for the extended study and followed the 97 patients who were administered either 4 ml Ampion or saline vehicle control for an additional 8 weeks.

Why is patient participation in the 8-week extension study so low?

Let's do some math: The "Spring" study enrolled 329 patients, equally randomized to four arms -- 4 ml Ampion and a matching placebo or 10 ml Ampion and a matching placebo. That means each arm had 82 patients, or 164 patients in the 4 ml Ampion/matching placebo arms.

By Ampio's own admission, only 97 patients, or 59%, treated with either 4 ml of Ampion or matching placebo chose to enter the extension study. That's a relatively small percentage of patients choosing to move forward into the extension study, which could have (should have) been closer to 80-90% based on the purported efficacy of Ampion. These patients didn't receive further injections of Ampion or placebo, they were simply followed for another 8 weeks.

On a related note, Ampio has never disclosed patient discontinuation rates from the Ampion "Spring" study. How many of the 329 patients enrolled completed 12 weeks of treatment? If patients dropped out, why? How did drop outs compare across the Ampion and placebo arms of the study? And how were drop outs accounted for in the analysis of the study?

There are a lot of unanswered questions about Ampio's "Spring" study of Ampion.

-- Reported by Adam Feuerstein in Boston.

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Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.

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