CYTK's Omecamtiv Mecarbil PDUFA and Cardiac Readouts!

Summary:

• The CYTK PDUFA for Omecamtiv Mecarbil is coming up on February 28 for heart failure with reduced ejection fraction (HErEF)

• The Dec 13 AdComm vote was negative: committee voted 8-3 that Omecamtiv benefits do not outweigh risks

• Other exciting heart failure assets in 2023 include the ESPR presentation in March and two additional PDUFA decisions!

CYTK's asset Omecamtiv Mecarbil has a PDUFA target action date of February 28, 2023 for the possible treatment of heart failure with reduced ejection fraction (HErEF). Omecamtiv Mecarbil is a selective cardiac myosin activator. Currently Omecamtiv mecarbil is the only cardiac myosin activator in our database that includes all smid-cap biopharmas.

Two Phase 3 trials have been completed to evaluate Omecamtiv Mecarbil for heart failure: GALACTIC-HF (a cardiovascular outcomes study in partnership with AMGN) and METEORIC-HF (an exercise capacity study). The GALACTIC-HF trial evaluated the lowering of adverse cardiac outcomes through improving contractility in heart failure. GALACTIC-HF evaluated 8000 patients in 35 countries and demonstrated a statistically significant effect in the primary composite endpoint of reducing the risk of cardiovascular (CV) death or heart failure events from Omecamtiv compared to the standard of care. The secondary endpoint of time to CV death was not reduced in this trial. Topline data from this collaboration trial was reported in October 2020 by AMGN, after which point CYTK took over the asset. This trial led to the filing of the NDA for Omecamtiv Mecarbil in 2021 and additional results were reported at CVCT in December 2020 as well as a secondary analysis of the trial was presented at ACC in May 2021.

This Phase 3 trial was an outcomes trial, similar to the ESPR CLEAR outcomes trial that first reported data in December 2022. The ESPR CLEAR cardiovascular outcomes trial of NEXLETOL met the primary endpoint with statistical significance - demonstrating reduction in major adverse cardiovascular events compared to the placebo. NEXLETOL is approved to treat adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease. While it was first announced in December 2022 that the trial met the primary endpoint, data was not reported, and will be presented at ACC in March 2023. It will be interesting to see how this compares to the GALACTIC-HF outcomes study.

The second Phase 3 trial evaluating Omecamtiv mecarbil was the METEORIC-HF trial to evaluate exercise capacity by cardiopulmonary exercise testing after 20 weeks of omecamtiv mecarbil treatment. Topline data was reported on Feb 15, 2022 and the primary endpoint was to monitor the change in peak oxygen uptake on CPET from baseline to 20 weeks of treatment. There was no effect on the primary endpoint from Omecamtiv mecarbil. Adverse events including major cardiac events were similar to prior trials including GALACTIC-HF. Currently therapies to treat heart failure have been elusive in demonstrating improvement in exercise capacity, and the METEORIC-HF data was neutral.

After the NDA for Omecamtiv mecarbil was accepted, the initial PDUFA date was set at November 30, 2022. However, additional data was provided by CYTK and the PDUFA was extended by three months to Feb 28, 2023. An AdComm meeting was also scheduled for December 13, 2022. The vote from this meeting was negative, with a vote of 8-3 against Omecamtiv mecarbil stating the benefits do not outweigh the risks. Interestingly, even with the negative vote, stock rose 8% upon announcement of the vote.

There are many other exciting heart failure & heart disease catalysts in our database with upcoming events including ESPR Outcomes data and multiple PDUFAs! See Table 1 for these readouts, and more!

Table 1.  Upcoming cardiac readouts

Hedge funds and CYTK

CYTK was held in 8 of the 35 biotech hedge funds we tracked in Q3 2022. While completing our Q3 2022 hedge fund analysis, we determined that a company held in more than 6 of the hedge funds was a lot, so CYTK being held by 8 funds in impressive! We look forward to Q4 hedge fund data, coming in the middle of February, to see how many were holding CYTK at the end of 2022. Below are the hedge funds holding CYTK at the end of Q3 2023 and the percentage of the portfolio made up by CYTK.

Opaleye Management: 5.26% (Top 6 of this fund)

Logos Global Management: 10.13% (Top 2 of this fund)

Palo Alto Investors: 0.43%

Sofinnova Investments: 0.90%

Boxer Capital: 5.72% (Top 2 of this fund)

RTW Investments: 2.88%

Bioimpact Capital: 2.22%

DAFNA Capital Management: 2.40%

We are very excited for the CYTK PDUFA in February and beyond as heart failure and cardiac assets are in the spotlight.

This article is NOT legal, investment or tax advice. Please do your own diligence before making any investments.

Article history:

Originally posted 2/3/23