UPDATED: Astellas walks away from $450M+ Cytokinetics pact after taking a few extra months to see progress
Months after losing longtime partner Amgen on its lead heart drug, Cytokinetics is waving goodbye to another ally — and with it, more than $450 million in potential milestones.
Cytokinetics said in an SEC filing last week that Astellas is officially walking away from a pact to research skeletal sarcomere activators for diseases associated with muscle weakness. The companies had extended the research term of their partnership — which was initially set to expire on Dec. 31 — through March of this year to finish work they couldn’t get done during the pandemic, Cytokinetics CEO Robert Blum told Endpoints News. But on April 27, Astellas gave written notice that it’s hitting the exit.
According to the filing, Astellas is giving up “all licenses and other rights” granted through the pact.
The research, development and commercialization pact was initially struck back in 2013. But in April 2020, Astellas returned the rights to reldesemtiv, Cytokinetics’ candidate to treat muscle wasting, and other fast skeletal regulatory activator (FSRA) compounds that were subject to the original agreement. Astellas agreed to pay one-third of the out-of-pocket costs for Cytokinetics’ continued Phase III trial for the drug in ALS, in return for “low- to mid-single digit” royalties in the US, Canada, UK and EU for either 10 years after the first sale, or until 2034, according to an SEC filing.
“The research program that was extended was done with joint agreement, just so we could wind down on a couple of matters that we agreed we wanted to put to bed before we stepped away,” Blum said. “We jointly decided that we were going to finish the research together, and then go our separate ways.”
Endpoints reached out to Astellas, but did not receive a response as of press time.
Cytokinetics is left without the opportunity to scoop up some major milestones laid out in the original deal. According to the deal, Astellas could have nabbed exclusive rights to co-develop and sell the skeletal sarcomere activators in all indications, leaving Cytokinetics the right to co-promote and do certain sales work in the US, Canada and/or Europe “under agreed scenarios.”
If Astellas wanted to take any of the candidates forward on its own, it would have owed Cytokinetics $25 to $35 million per product, plus up to $250 million more for all products and another $200 million in commercial milestones. On top of all that, Cytokinetics would have been set to receive royalties in the “mid-single-digit level to low double-digits.”
The news comes about two years after reldesemtiv flopped in a Phase II ALS trial. At the time, investigators said the study failed on change from baseline in slow vital capacity (SVC) after 12 weeks of dosing (p=0.11). The analysis also showed poor p-values for the ALS Functional Rating Scale and slope of the Muscle Strength Mega-Score.
But despite failing the primary endpoint, the company argued that the data reflected “clinically meaningful magnitudes of effect” across all dose levels, and maintained that the placebo group declined at a slower rate than expected, which didn’t help.
“Results from FORTITUDE-ALS are among the most impressive we have seen in a Phase II clinical trial in ALS,” lead investigator Jeremy Shefner said back in 2019.
That wasn’t the first or last time Cytokinetics has touted weak or failed data. Back in November, the company cheered a Phase III readout for its Amgen-partnered heart drug omecamtiv mecarbil. But while the candidate met the primary composite endpoint, it missed a secondary endpoint which analysts had been following as a key marker for success — reduction of cardiovascular death.
Later that month, Amgen shrugged off its 14-year alliance with Cytokinetics, leaving the company to soldier on alone.
“Cardiovascular disease is one of the most significant public health issues in the world which means patients need more innovation, not less,” Amgen said in a statement. “… Unfortunately, the results of GALACTIC-HF did not meet the high bar we had set for the program.”