Expert Financial Analysis and Reporting

Key Points

• Results from the COSMIC HF phase 2 trial of omecamtiv mecarbil support the hypothesis that it improves heart function and (very importantly) reverses structural damage in patients with heart failure. Side effects are comparable to placebo.
• If these results are replicated in the GALACTIC-HF phase 3 trial, I believe that omecamtiv mecarbil has peak annual sales potential of $10 to $15 billion.
• Amgen and Cytokinetics announced that the Phase 3 GALACTIC HF trial has started. It will enroll around 8000 patents. Topline data could be available in mid-2021. See this link for more details on the trial.
• These results support my price target objective of over $20 on the stock. See my report of November 4, 2016 My Relative Market Value Analysis Suggests that the Stock Should be Selling at More Than $20

COSMIC-HF Results Published in The Lancet

Amgen and Cytokinetics announced that results from the phase 2 COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure) trial of omecamtiv mecarbil in patients with chronic heart failure were published in the prestigious medical journal The Lancet. Amgen stated that the results were striking as the hearts of patients treated with omecamtiv were able to pump higher volumes of blood with fewer beats per minute. Sean Harper, head of research at Amgen stated that this was consistent with the hypothesis that omecamtiv actually reverses structural damage caused by heart failure. Importantly, the side effect profile was comparable to placebo.

If these results are duplicated in a phase 3 trial, omecamtiv should be a viewed as a major medical breakthrough and would be added to standard of care for most heart failure patients. The commercial potential would be enormous. The incidence of heart failure is extremely high at 23 million people worldwide according to Amgen. There have been numerous drugs of the ACE and ARB II class that were used to treat symptoms of heart failure that reached several billions of dollars of annualized sales individually and well over $10 billion collectively. I think that the commercial potential for omecamtiv mecarbil may be on the order of $10 to $15 billion at peak sales.

Amgen’s Summary of Efficacy Results in COSMIC-HF

COSMIC-HF evaluated 448 patients with chronic heart failure and left ventricular systolic dysfunction, showed that dose titration controlled patient exposure to omecamtiv mecarbil. Patients were randomized 1:1:1 to receive either placebo or treatment with omecamtiv mecarbil dosed as 25 mg twice daily or 25 mg with dose escalation to 50 mg twice daily, depending on plasma concentrations of omecamtiv mecarbil after two weeks of treatment.

The pharmacokinetic-based dose titration strategy was designed to maintain patient exposure to omecamtiv mecarbil in the targeted plasma concentration range. Approximately 53 percent of patients in the dose titration group were escalated to a dose of 50 mg twice daily.

Following 20 weeks of treatment, statistically significant improvements were observed in all pre-specified secondary endpoint measures of cardiac function in the dose titration group, compared to placebo. Systolic ejection time increased by 25.0 msec (p<0.0001), stroke volume increased by 3.6 mL (p=0.0217) and heart rate decreased by 3.0 beats per min (p=0.0070). Left ventricular end-systolic and end-diastolic dimensions decreased by 1.8 mm (p=0.0027) and 1.3 mm (p=0.0128), respectively, and were associated with statistically significant reductions in left ventricular end-systolic and end-diastolic volumes. N-terminal pro-brain natriuretic peptide (NT-proBNP) decreased by 970 pg/mL (p=0.0069). In pre-specified exploratory analyses of the dose titration group, placebo-corrected reductions in NT-proBNP persisted four weeks after stopping omecamtiv mecarbil, decreasing further to 1306 pg/mL (p=0.0006). The data also showed increases in fractional shortening at week 20 compared to placebo in the dose titration group.

Amgen’s Summary of Side Effects in COSMIC-HF

Adverse events (AEs), including serious AEs, in patients on omecamtiv mecarbil were comparable to placebo. The incidence of adjudicated deaths (3 percent died on placebo, 1 percent died on omecamtiv mecarbil 25 mg twice daily, 2 percent died on omecamtiv mecarbil dose titration), myocardial infarction (1 percent on placebo, 0 percent on omecamtiv mecarbil 25 mg twice daily, 1 percent on omecamtiv mecarbil dose titration) and unstable angina (0 percent on placebo, 1 percent on omecamtiv mecarbil 25 mg twice daily, 0 percent on omecamtiv mecarbil dose titration) was similar. Other cardiac AEs were generally balanced between placebo and active treatment groups. In patients receiving omecamtiv mecarbil compared to placebo, cardiac troponin increased by 0.001 ng/mL and 0.006 ng/mL (median change from baseline at week 20) in the 25 mg twice daily group and dose titration group, respectively. Events of increased troponin (n=278 across all treatment groups) were independently adjudicated and none were adjudicated as an episode of myocardial ischemia or infarction.

GALACTIC-HF: Trial Design

GALACTIC-HF is planned to enroll approximately 8,000 symptomatic chronic heart failure patients in over 800 sites in 34 countries who are either currently hospitalized for a primary reason of heart failure or have had a hospitalization or admission to an emergency room for heart failure within one year prior to screening. ClinTrials.gov states that the final data collection for the trial will occur in March 2021. If so, topline data would be available in mid-2021.

In order to be eligible to participate in GALACTIC-HF patients should have an LVEF ≤ 35%, be NYHA class II to IV, and have an elevated BNP or NT-proBNP. Patients will be randomized to either placebo or omecamtiv mecarbil with dose titration up to a maximum dose of 50 mg twice daily based on the plasma concentration of omecamtiv mecarbil after initiation of drug therapy.

The primary endpoint is a composite of time to cardiovascular death or first heart failure event, which is defined as either a hospitalization for heart failure or other urgent treatment for worsening heart failure. Secondary endpoints include time to cardiovascular death; patient reported outcomes as measured by the Kansas City Cardiomyopathy Questionnaire Total Symptom Score; time to first heart failure hospitalization; and all-cause death.