BioCryst Announces Positive Results from its APeX-1 Phase 2 Trial in HAE
73% Reduction in Overall Attack Frequency at 125mg Dose (p < 0.001)
"We are delighted to see a robust treatment effect after completing the largest ever Phase 2 trial in HAE patients. We now have the information necessary to select doses for Phase 3," said Jon Stonehouse, Chief Executive Officer & President. "The 125 mg once-daily oral dose of BCX7353 provided a high level of efficacy and excellent tolerability. This product profile will be an extremely attractive treatment option for physicians and patients."
"An effective and tolerable prophylaxis of hereditary angioedema attacks is of paramount importance for many HAE patients and the benefit of an oral administration route for these chronically ill patients cannot be overestimated. In that respect, the
results of this trial are extremely encouraging for the HAE patient community," said Dr. Emel Aygören-Pürsün, MD, principal investigator for the APeX-1 trial and Head of
"With an active IND in the
Seventy-five subjects were randomized and included in the final analysis of pooled data from Parts 1, 2 and 3: 7 at 62.5 mg, 14 at 125 mg, 14 at 250 mg and 18 at 350 mg of BCX7353 QD; and 22 placebo. The qualifying attack rate was approximately 1/week. Baseline characteristics were generally well balanced across the treatment groups. Compliance with daily study drug dosing for 28 days was excellent (≥ 98% across all treatment groups).
Subjects recorded angioedema symptoms in a diary; diary records were reviewed and attacks adjudicated by an independent expert group. The primary endpoint of the trial was the number of HAE attacks. The pre-specified per-protocol (PP) final analysis included data on a total of 67 subjects with Type 1 or Type 2 HAE completing > 90% of planned study drug doses. The percentage reductions by treatment group in the mean rate of angioedema attacks for the pre-defined effective dosing period (weeks 2 through 4) in BCX7353 treated subjects are indicated in the Table below. Results from a pre-planned analysis of peripheral and abdominal attacks are also shown. Similar results to those shown were seen in the analysis of weeks 1 through 4 and the intent-to-treat population (ITT).
| Percentage change in attacks vs placebo (p-Value) | ||||||||||
| Per protocol population, weeks 2-4 of treatment | ||||||||||
| N | All Attacks | Peripheral Attacks | Abdominal Attacks | |||||||
| BCX7353 350 mg | 14 | -58% (p < 0.001) | -90% (p < 0.001) | -5% (p=0.884) | ||||||
| BCX7353 250 mg | 12 | -46% (p=0.006) | -66% (p=0.005) | -13% (p=0.700) | ||||||
| BCX7353 125 mg | 13 | -73% (p < 0.001) | -79% (p < 0.001) | -63% (p=0.048) | ||||||
| BCX7353 62.5 mg | 7 | -7% (p=0.715) | -25% (p=0.371) | +22% (p=0.578) | ||||||
The 125 mg dose level showed statistically significant and similar benefit for all attacks, and also when split into abdominal attacks and peripheral attacks. In contrast, at the 250 mg and 350 mg dose levels, there was no statistically significant effect for abdominal attacks, despite strong and statistically significant effects on peripheral attacks. Based on these findings, it is likely that subjects in the 250 mg and 350 mg arms recorded transient drug-related abdominal adverse events (AEs) as HAE attack symptoms in their diary. As expected, the lowest dose tested (62.5 mg QD) showed no statistically significant differences in attack rates (total, or when split into abdominal and peripheral) compared with placebo. The range of doses studied and associated results complete the dose response evaluation required to inform Phase 3 dose selection.
A significant increase in the proportion of attack-free subjects was observed in the 125 mg QD dose group compared to placebo (46% versus 10%, p= 0.033). Furthermore, a clinically important and statistically significant improvement in patient quality of life total score, measured using the AE-QoL instrument, was seen in the 125 mg QD group compared to placebo (p < 0.001). The mean improvement in the 125 mg QD group was more than four times the minimum clinically important difference.
Oral BCX7353 once-daily for 28 days was generally safe and well tolerated in subjects with HAE. No new clinically significant safety findings were seen in Part 3 of the trial. Overall, there was one serious adverse event of moderate gastrointestinal infection that was determined by the investigator not to be drug-related. As previously reported, study drug was discontinued before day 28 in three subjects in the BCX7353 350 mg treatment arm (unrelated pre-existing liver disorder; related gastroenteritis with liver disorder; and related vomiting/abdominal cramps). The most common treatment-emergent AEs in descending order of frequency were the common cold, headache, diarrhea, nausea and abdominal pain. Gastrointestinal AEs were infrequent at the 125 mg and 62.5 mg dose levels, and there were no clinically significant laboratory abnormalities at these dose levels.
Steady state BCX7353 plasma levels and kallikrein inhibition levels were consistent with previous analyses. Steady state trough drug levels (24 hours after dosing) exceeded the proposed target threshold for efficacy of 4 times the 50% effective concentration (EC50) in 0%, 64%, 100% and 100% of subjects at the 62.5 mg, 125 mg, 250 mg and 350 mg dose levels, respectively.
The observed efficacy, dose response, PK, safety and tolerability profile of BCX7353 strongly support its advancement into Phase 3 development. BioCryst intends to meet with the
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Forward-Looking Statements
This press release contains
forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause BioCryst's actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: that developing any HAE drug candidate may take longer or may be more expensive than planned; that ongoing and future preclinical and clinical development of HAE
second generation drug candidates (including APeX-1 and ZENITH-1) may not have positive results; that BioCryst may not be able to enroll the required number of subjects in planned clinical trials of product candidates; that the Company may not advance human clinical trials with product candidates as expected; that the
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CONTACT:Thomas Staab ,BioCryst Pharmaceuticals , +1-919-859-7910
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