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Hi guys, I just need some help in developing any ideas for the following assignment, any help would be appreciated:
Metapharm based in Westminster, Colorado, has positive results from its Phase IIb clinical trial of Placado (dihydrogenoxide hydrochloride) for patients with atrial fibrillation (AF).
Your diligence suggests there may have been some cherry-picking of the data to give the outcome a more positive spin, rather than a suggested moderate, or potentially negative results.
The company’s clinical trial, Silametic-AF, evaluated 267 patients from the U.S., Canada and Europe. Patients had AF with heart failure and reduced left ventricular ejection fraction (HFrEF). All patients showed a similar benefit compared to the active control, metoprolol succinate (TOPROL-XL). This indicates it did not demonstrate superiority, which was one of the pre-hoc endpoints of the trial. However, in certain population subsets, it did show superiority. The company notes that non-inferiority to the standard of care IS in fact a tenet of US recognition of efficacy.
In the U.S. patients, with first diagnosis of malignant AF, 127 of 267 total patients demonstrated a numerical trend toward superior benefit, showing about a 30 percent risk reduction over TOPROL-XL. A similar trend was shown in a subset of patients whose heart rhythm was continuously monitored with an implanted device, showing about a 51 percent risk reduction over TOPROL-XL.
The primary endpoint of the trial was a composite of time to recurrent AF, atrial flutter (AFL) or all-cause mortality (ACM).
In this regard the company noted, “The trial was not powered to conventional significance for its endpoint and utilized Bayesian statistical modeling of predictive probability of success (PPoS) of the primary endpoint to estimate outcome if the trial had enrolled 620 patients with 330 primary events.”
Placado is a beta-blocker and mild vasodilator. Originally developed by Huge Pharma the active pharmaceutical ingredient, dihydrogenoxide hydrochloride,has been previously clinically tested in about 4,500 patients, including more than 3,250 patients in eight clinical trials in HFrEF patients.
“We are pleased to share these results from our GENETIC-AF clinical trial,” said Nick Tesla Metapharm’s ’s president and chief executive officer, in a statement. “It should be emphasized that the control drug in the study, TOPROL-XL, although not FDA approved for this indication, has demonstrated an unexpected degree of efficacy in preventing AF in HFrEF. While we did observe some regional heterogeneity in effectiveness of PLACADO, we believe the treatment response observed in thedefined sunset of the U.S. population, which represents approximately half of the overall study population, support continued development of PLACDO as a genetically-targeted treatment for atrial fibrillation.
As in all Phase II trials, which in part are conducted to elicit information relevant to the design for Phase III, elucidation of the reason(s) for regional heterogeneity could prove valuable for Phase III trial design.”
The company plans to meet with the U.S. Food and Drug Administration (FDA) in the second quarter of this year to review the Phase II data and develop a Phase III plan and trial structure.
Business Development of your company appears doubtful as to this investment, but many clinical trials are being built on subpopulation results, so the company may have a route forward, particularly given that the company’s focus is on genetically-identified treatments.
Make a PRO or CON argument to acquire this asset and continue development. Consider validity of the current development program and IF PRO, how the development plan may be derisked and accelerate approval.
Metapharm based in Westminster, Colorado, has positive results from its Phase IIb clinical trial of Placado (dihydrogenoxide hydrochloride) for patients with atrial fibrillation (AF).
Your diligence suggests there may have been some cherry-picking of the data to give the outcome a more positive spin, rather than a suggested moderate, or potentially negative results.
The company’s clinical trial, Silametic-AF, evaluated 267 patients from the U.S., Canada and Europe. Patients had AF with heart failure and reduced left ventricular ejection fraction (HFrEF). All patients showed a similar benefit compared to the active control, metoprolol succinate (TOPROL-XL). This indicates it did not demonstrate superiority, which was one of the pre-hoc endpoints of the trial. However, in certain population subsets, it did show superiority. The company notes that non-inferiority to the standard of care IS in fact a tenet of US recognition of efficacy.
In the U.S. patients, with first diagnosis of malignant AF, 127 of 267 total patients demonstrated a numerical trend toward superior benefit, showing about a 30 percent risk reduction over TOPROL-XL. A similar trend was shown in a subset of patients whose heart rhythm was continuously monitored with an implanted device, showing about a 51 percent risk reduction over TOPROL-XL.
The primary endpoint of the trial was a composite of time to recurrent AF, atrial flutter (AFL) or all-cause mortality (ACM).
In this regard the company noted, “The trial was not powered to conventional significance for its endpoint and utilized Bayesian statistical modeling of predictive probability of success (PPoS) of the primary endpoint to estimate outcome if the trial had enrolled 620 patients with 330 primary events.”
Placado is a beta-blocker and mild vasodilator. Originally developed by Huge Pharma the active pharmaceutical ingredient, dihydrogenoxide hydrochloride,has been previously clinically tested in about 4,500 patients, including more than 3,250 patients in eight clinical trials in HFrEF patients.
“We are pleased to share these results from our GENETIC-AF clinical trial,” said Nick Tesla Metapharm’s ’s president and chief executive officer, in a statement. “It should be emphasized that the control drug in the study, TOPROL-XL, although not FDA approved for this indication, has demonstrated an unexpected degree of efficacy in preventing AF in HFrEF. While we did observe some regional heterogeneity in effectiveness of PLACADO, we believe the treatment response observed in thedefined sunset of the U.S. population, which represents approximately half of the overall study population, support continued development of PLACDO as a genetically-targeted treatment for atrial fibrillation.
As in all Phase II trials, which in part are conducted to elicit information relevant to the design for Phase III, elucidation of the reason(s) for regional heterogeneity could prove valuable for Phase III trial design.”
The company plans to meet with the U.S. Food and Drug Administration (FDA) in the second quarter of this year to review the Phase II data and develop a Phase III plan and trial structure.
Business Development of your company appears doubtful as to this investment, but many clinical trials are being built on subpopulation results, so the company may have a route forward, particularly given that the company’s focus is on genetically-identified treatments.
Make a PRO or CON argument to acquire this asset and continue development. Consider validity of the current development program and IF PRO, how the development plan may be derisked and accelerate approval.
