Achaogen Inc (NASDAQ:AKAO) announced that its lead product candidate, plazomicin, met the objective of non-inferiority compared to meropenem for the U.S. Food and Drug Administration (FDA) and achieved superiority for the European Medicines Agency (EMA) primary efficacy endpoints in the Phase 3 EPIC registration trial in patients with complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). In addition, in the Phase 3 CARE trial in patients with serious infections due to carbapenem-resistant Enterobacteriaceae (CRE) a lower rate of mortality or serious disease-related complications was observed for plazomicin compared with colistin therapy, one of the few remaining antibiotics for treatment of infections due to CRE.
“We are thrilled with the outcome of both the EPIC and CARE clinical trials and the potential opportunity for plazomicin to address many of the multi-drug resistant bacterial infections occurring every day,” said Kenneth Hillan, M.B. Ch.B., Achaogen’s Chief Executive Officer. “We are grateful to the patients and investigators who were involved in both of these studies, and we look forward to seeking plazomicin’s approval from FDA and EMA. We believe that, if approved, plazomicin will provide an important new option in treating MDR infections, including those caused by CRE.”
Achaogen plans to submit a New Drug Application (NDA), which will include EPIC and CARE data, to the FDA in the second half of 2017. The Company also plans to submit a Marketing Authorization Application (MAA) to the EMA in 2018. In addition, Achaogen plans to publicly present detailed results from both the EPIC and CARE trials in 2017.
“These data are exceptional and better than I would have expected – plazomicin’s superiority in microbiologic cure for patients with cUTI at the test-of-cure visit compared to meropenem, a gold standard for treating MDR infections, is impressive. Importantly, the safety profile of the drug looks favorable,” said James A. McKinnell, Assistant Professor of Medicine at the David Geffen School of Medicine and LA Biomed at Harbor-UCLA. “The data from the CARE trial provides compelling evidence for plazomicin as a treatment option for serious infections due to CRE. The sample size for the CARE study was small, but the data show a clear trend in favor of plazomicin in terms of efficacy and overall safety compared to colistin. CRE infections cause serious morbidity and mortality and seem to be on the rise. Based on these data, plazomicin would be a valuable addition to my short list of available treatment options for both empiric and directed treatment of patients, and as a single agent or in combination with other antibiotics.”
In the EPIC trial, plazomicin successfully met the objective of non-inferiority compared to meropenem for the FDA-specified primary efficacy endpoints, and achieved superiority for the EMA-specified primary efficacy endpoints.
Results for FDA pre-specified composite endpoint of clinical cure and microbiological eradication in the microbiological modified intent-to-treat (mMITT) population were as follows:
- Day 5: 88.0% plazomicin vs. 91.4% meropenem (difference -3.4%, 95% CI: -10.0, 3.1%), indicating statistical non-inferiority
- Test-of-Cure: 81.7% plazomicin vs. 70.1% meropenem (difference 11.6%, 95% CI: 2.7, 20.3%), indicating statistical superiority
Results for EMA-specified endpoints of microbiological eradication at the test-of-cure visit were as follows:
- mMITT: 87.4% plazomicin vs. 72.1% meropenem (difference 15.4%, 95% CI: 7.5, 23.2%), indicating statistical superiority
- ME: 90.5% plazomicin vs. 76.6% meropenem (difference 13.9%, 95% CI: 6.3, 21.7%), indicating statistical superiority
Phase 3 EPIC Trial in Patients with cUTI: Summary of FDA and EMA Primary Efficacy Endpoints
(* indicates statistical superiority)
|Composite endpoint at Day 5, mMITT (FDA)||168/191 (88.0%)||180/197 (91.4%)||-3.4% |
|Composite endpoint at TOC, mMITT (FDA)||156/191 (81.7%)||138/197 (70.1%)||11.6%|
|Microbiological eradication at TOC, mMITT (EMA)||167/191 (87.4%)||142/197 (72.1%)||15.4% |
|Microbiological eradication at TOC, ME (EMA)||162/179 (90.5%)||134/175 (76.6%)||13.9%|
CI: confidence interval; ME: microbiologically evaluable; mMITT: microbiological modified intent-to-treat; TOC: test-of-cure;a Difference = plazomicin minus meropenem
Plazomicin was well tolerated with no new safety concerns identified in the EPIC trial. Total treatment emergent adverse events (TEAEs) related to renal function were reported in 3.6% and 1.3% of patients in the plazomicin and meropenem groups, respectively. TEAEs related to cochlear or vestibular function were reported in a single patient in each of the plazomicin and meropenem treatment groups. Both events were considered mild and resolved completely.
In the Phase 3 CARE trial in patients with serious infections due to CRE a lower rate of mortality or serious disease-related complications was observed for plazomicin compared with colistin therapy.
Results from the CARE trial were as follows:
- Day 28 all-cause mortality or significant disease related complications (primary endpoint); 23.5% plazomicin vs. 50.0% colistin (difference 26.5%, 90% CI: -0.7, 51.2%)
- Day 28 all-cause mortality; 11.8% plazomicin vs. 40.0% colistin (difference 28.2%, 90% CI: 0.7, 52.5%)
Phase 3 CARE Trial in Patients with BSI or HABP/VABP due to CRE
(Cohort 1 mMITT population)
|Day 28 all-cause mortality or significant disease-related complications||4/17 (23.5%)||10/20 (50.0%)||26.5%|
|Day 28 all-cause mortality||2/17 (11.8%)||8/20 (40.0%)||28.2%|
a Difference = colistin minus plazomicin
The safety profile of plazomicin was favorable to that of colistin in critically ill patients in the CARE trial. Study drug-related TEAEs related to renal function were reported in 16.7% and 38.1% of patients in the plazomicin and colistin groups, respectively. No TEAEs related to cochlear or vestibular function were reported in either group. (Original Source)
Shares of Achaogen jumped today over 90% to $9.08. AKAO has a 1-year high of $9.39 and a 1-year low of $2.59. The stock’s 50-day moving average is $4.95 and its 200-day moving average is $4.33.
On the ratings front, Achaogen has been the subject of a number of recent research reports. In a report issued on November 28, Cowen analyst Ritu Baral reiterated a Buy rating on AKAO. Separately, on November 8, Needham’s Alan Carr reiterated a Hold rating on the stock.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Ritu Baral and Alan Carr have a yearly average return of 1.2% and 6.8% respectively. Baral has a success rate of 36% and is ranked #1707 out of 4273 analysts, while Carr has a success rate of 44% and is ranked #521.
Achaogen, Inc. operates as a clinical-stage biopharmaceutical company. It discovers, develops and commercializes novel antibacterials to treat multi-drug resistant (MDR) gram-negative infections. develops plazomicin for the treatment of serious bacterial infections due to MDR enterobacteriaceae, including carbapenem-resistant enterobacteriaceae.