Cytokinetics Inc. as a competitor for Myokardia Inc.’s cardiovascular (CV) drug, mavacamten, didn’t come up until near the end of the conference call related to the $13.1 billion buyout of the latter company by Bristol Myers Squibb Co. (BMS), but the prospect is on Wall Street’s mind.
New York-based BMS is paying $225 per share for Myokardia, of Brisbane, Calif., to add to its CV lineup mavacamten, an allosteric modulator of cardiac myosin for obstructive hypertrophic cardiomyopathy (HCM). The stock (NASDAQ:MYOK) closed at $220.34, up $80.74, or 58%.
Well known as molecular “motors,” myosins consume chemical energy in the form of ATP and produce mechanical force and movement needed for diverse biological processes, such as muscle contraction and cell motility. Mavacamten’s NDA, due early next year, will be based on data from the trial called Explorer-HCM, which met its primary and all secondary endpoints, showing meaningful improvements in symptoms, functional status and quality of life by reducing the obstruction of blood flow from the heart. BMS, of New York, said it expects to explore the compound’s potential in non-obstructive HCM as well, while working with other prospects in the Myokardia pipeline.
The buyout of Myokardia comes as BMS continues to integrate Summit, N.J.-based Celgene Corp., acquired for $74 billion at the start of 2019. Wolfe research analyst Timothy Anderson was forthright on the conference call, asserting that with Celgene still being folded into BMS, “layering in another [deal] at this stage is kind of surprising and unusual. Some investors are bound to ask whether there's any sort of problem elsewhere in your business that you might be trying to backfill on, either late-stage pipeline assets or in-line brands. Can you assure us that this is not the case, and that your confidence in everything you've laid out since the Celgene deal was announced is just as high as ever, including some of the upcoming readouts?”
BMS CEO Giovanni Caforio said that “it's really because of the strong foundation that we've established, and the fact that we feel really good about where we are as a company, that we can continue to advance our strategy.” BMS will “continue to look at opportunities as they come,” with a preference for “small, science-driven deals” but a willingness to make bigger transactions if the assets justify doing so. “This [Myokardia buyout] is not just the right asset – it’s also the right time,” he said, as BMS wanted to work with the company on its regulatory filing. BMS already markets the oral anticoagulant Eliquis (apixaban), first approved in late 2012 to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation that is not caused by a heart valve problem. Eliquis is partnered with New York-based Pfizer Inc. Cowen analyst Ritu Baral was optimistic, estimating mavacamten peak U.S. and EU sales of $3.8 billion and $2 billion by 2028 and 2029, respectively. The company is also developing MYK-491 (danicamtiv) for the treatment of dilated cardiomyopathy, a disease that affects nearly 2 million patients, and has generated encouraging phase II proof-of-concept data.
Buzz already has begun about the meaning of the BMS/Myokardia deal for Cytokinetics Inc., of South San Francisco, which has plenty going on. Galactic-HF, the pivotal outcomes trial testing cardiac myosin activator omecamtiv mecarbil in patients with heart failure (HF), is nearing the finish line and is expected to report top-line data this quarter. Most of the events required to determine the study endpoints have taken place, and Galactic-HF passed the second interim analysis, set at two-thirds of 1,590 events of CV death. “Preparatory activities to ensure readiness for commercialization and regulatory meetings are ongoing” in collaboration with global partner Amgen Inc., of Thousand Oaks, Calif., Wainwright analyst Joseph Pantginis noted in a report. Also underway is the phase III experiment called Meteoric HF, testing omecamtiv in improving exercise capacity in patients with HF, with 75% of the targeted 92 sites already activated across various countries. Signups should be complete early next year. “While Meteoric-HF could set the stage for omecamtiv's possible label expansion and supporting the use of the drug in patients with HF, at the moment, the outcome results of Galactic-HF remain the ones critical for omecamtiv's approval,” he said. “Importantly, the data from Meteoric-HF are not necessary for omecamtiv approval, but could be added in a supplemental filing following a commercial launch of the drug, should Galactic-HF be positive.” Cytokinetics also has underway the phase II Redwood-HCM study, evaluating myosin inhibitor CK-274 in patients with obstructive HCM. First-cohort results are expected by the end of this year.
“All focus has been on mavacamten's phase III positive data in obstructive HCM, and [the compound] is in a phase II [trial] for non-obstructive HCM,” Pantginis said. “A follow-on asset, MYK-224 is also in a phase I for HCM, as well as two earlier-stage assets for diastolic and systolic heart failure.” With Cytokinetics, the question is whether Amgen “or even someone else” will choose to scoop up the company. Amgen “really makes the most sense to us,” he said. “We have spent a significant amount of time highlighting CK-274, and believe it is a differentiated asset, especially based on the therapeutic window, potentially reducing any drug titration issues.” Shares of Cytokinetics (NASDAQ:CYTK) closed at $28.61, up $4.62, or 19%.
BMS’ chief medical officer, Samit Hirawat, said that “the Cytokinetics compound certainly is going to be there in a few years from now, and we will continue to observe as the data evolves.” Galactic-HF is testing omecamtiv in HF with reduced ejection fraction (HFrEF). Amgen enrolled 8,256 patients, of whom 2,083 (25%) were in-patient and 6,173 (75%) were outpatient. The primary endpoint is the composite of time to CV death or first HF event, and the trial is 90% powered on the secondary endpoint of time to CV death (N=1,590 deaths, HR=0.8, p<0.05). “Based on these criteria, Cytokinetics estimates greater than 99% statistical power on the primary composite endpoint,” Piper Sandler analyst Edward Tenthoff said in a report. Cytokinetics presented data at the Heart Failure Society of America meeting showing the severe medical need of HFrEF patients enrolled in Galactic. “We forecast blockbuster sales reaching $3 billion by 2028, with Cytokinetics retaining about a 20% net royalty,” he said. Amgen has an alliance with Les Laboratoires Servier SAS, of Suresnes, France, for exclusive commercialization rights to omecamtiv mecarbil in Europe as well as the Commonwealth of Independent States, including Russia.