|Wall Street Slams Cytokinetics on Phase II Miss, More Data Coming|
|By Brian Wilson-Lead Contributor|
|Wednesday, 04 September 2013 07:50|
Note that Omecamtiv mercabil is also referred to as CK-1827452 and AMG 423 in some of the literature.
The ATOMIC-AHF Study
ATOMIC-AHF was a 613 patient, randomized, double-blind and placebo-controlled Phase II study that started in April 2011 and ended at the start of this month (September 2013). Patients enrolled in the trial were adults that had already been hospitalized for heart failure in the left ventricle. These patients had not received particular drugs that strengthen the heart’s capacity to constrict, and were not on mechanical support.
The patients were divided into three escalating dose cohorts, and evaluated throughout a 48 hour period while on IV omecamtiv mercabil or placebo. The ratio between omecamtiv and placebo patients was 1:1.
The primary endpoint of ATOMIC-AHF was related to dyspnea (difficulty with breathing) in patients with worsening heart failure. To numerically evaluate this a 7-point Likert scale was used. A statistically significant improvement in the omecamtiv arm versus the placebo arm was not established (p=.33), although patient outcomes did improve with increased dosing of omecamtiv.
Note that a Likert scale is a questionnaire-styled survey which allows patients to respond to relevant questions with options ranging from “strongly disagree” to “strongly agree”. Secondary endpoints measuring efficacy included a pharmacokinetic endpoint which looked for a relationship between plasma concentration of omecamtiv mercarbil and certain echocardiographic parameters that can be correlated to death or worsening of heart failure.
The safety endpoints were established and met at the conclusion of the trial, although this was unsurprising. Omecamtiv mercabil has already established a strong safety profile during its Phase I development, which tested the drug on hundreds of patients.
While the failure of this trial was a setback for Cytokinetics and Amgen, it does not threaten the heavily supported development program for Omecamtiv mercabil. This trial studied patients in a very short timeframe with an unreliable primary endpoint. In addition, investors should note that the pharmacokinetic data is still quite valuable for the development program.
More important to the value of Omecamtiv mercabil later on is the final result of the COSMIC-HF trial, which has a similar design to ATOMIC-AHF but studies the oral formulation of the drug in patients over a much longer (12 week) timeframe. This trial not only has a better chance of success, but should establish a much better profile for the drug heading into Phase III development.
An Overview of the Cytokinetics Pipeline
Currently, Cytokinetics has three drug development programs that should constitute the bulk of its ~$225 M valuation. Here is a brief description of the three molecules and their development status:
Tirasemtiv (CK-2017357) – a molecule that activates fast skeletal muscles and increases cell sensitivity to signaling calcium over time. The drug is designed to increase the strength and speed of skeletal muscles to prevent degeneration. The drug is in three Phase II trials for Amyotrophic Lateral Sclerosis (AML), Myasthenia Gravis, and Claudication .
Omecamtiv Mercarbil (CK-1827452) –a novel small molecule that activates a protein that induces cardiac contraction. It is being evaluated as a treatment for heart failure. The drug recently concluded a Phase II trial ATOMIC-AHF and is close to completion of another Phase II trial referred to as COSMIC-HF.
CK-2127107 – a small molecule that is being investigated for its ability to sensitize fast skeletal muscles to signals that should induce contraction. A Phase I trial was initiated in April 2013.
Wall Street’s reaction to the data was a bit exaggerated, and Cytokinetics should at least be able to hold its ground after the current wave of selling dissipates. Anticipate vital Phase II data from the COSMIC-HF study closer to the middle of 2014, and possible plans for Phase III trials starting enrollment in the second half of the year.