Biogen entered into an agreement to jointly develop and commercialise Sage Therapeutics' zuranolone for major depressive disorder (MDD) and postpartum depression (PDD), as well as SAGE-324 for essential tremor, the companies announced Friday. Under the deal, Biogen will pay Sage $875 million in cash upfront, as well as up to $1.6 billion in potential milestones if the two drugs hit certain development and sales targets, whilst also taking a $650-million equity stake in the latter.
Zuranolone, a next-generation positive allosteric modulator of the GABAA receptor, is currently in late-stage development for MDD and PPD as part of the LANDSCAPE and NEST clinical programmes. According to the companies, the two-week, once-daily oral therapy, formerly dubbed SAGE-217, could potentially offer an "as-needed" short course of treatment for depressive episodes and ease difficulties associated with chronic use of antidepressants.
Biogen CEO Michel Vounatsos noted that major depression "is a common co-morbidity of multiple neurological disorders in [our] core therapeutic areas," such as multiple sclerosis, Alzheimer's disease and spinal muscular atrophy, adding "we are optimistic about the potential for zuranolone to help transform the treatment of depression and address the stigma often associated with chronic use of antidepressants."
Biogen said zuranolone 30 mg has so far completed two positive pivotal trials, Study MDD-201 in patients suffering from MDD, and the ROBIN study among PPD patients. However, Sage reported disappointing results in 2019 from the Phase III MOUNTAIN trial, in which zuranolone was not significantly better than placebo at alleviating MDD severity in adults as measured by a decrease on the Hamilton Rating Scale for Depression (HAM-D) baseline score.
Last month, the company released interim findings from the ongoing late-stage SHORELINE study showing that in a cohort of patients starting zuranolone treatment at a higher dose, 75% had a clinical response in terms of mean HAM-D change from baseline, with 48.1% achieving remission (for more analysis, see ViewPoints: Zuranolone passes SHORELINE but will it get Sage over the hump?). According to Biogen and Sage, both the SHORELINE results as well as "encouraging" recent follow-up data from MOUNTAIN suggest zuranolone "is clinically active in MDD."
Sage is also advancing other pivotal Phase III studies evaluating the higher 50-mg dose of zuranolone including SKYLARK in PPD patients, CORAL for patients with MDD when co-initiated with new standard antidepressant therapy, and WATERFALL for use as an acute treatment of MDD. Data for these studies along with the SHORELINE trial are anticipated in 2021. Meanwhile, SAGE-324 is another next-generation positive allosteric modulator of GABAA receptors. It is currently in Phase II development in the KINETIC trial for essential tremor, which is also expected to read out in 2021, with potential in other neurological conditions such as epilepsy and Parkinson's disease.
Biogen's equity investment involves the purchase of approximately 6.2 million shares of Sage at a price of $104.14 per share, representing a 26% premium to the latter's closing stock price on November 25. As part of the deal, Biogen and Sage will equally split responsibility and costs for development as well as profits and losses for commercialisation in the US. Outside the country, Biogen will handle development and marketing activities, excluding Japan, Taiwan and South Korea with respect to zuranolone, and will pay Sage tiered royalties in the high teens to low twenties.
The deal comes as Biogen and partner Eisai await a decision from the FDA on a marketing application seeking approval of the anti-amyloid antibody aducanumab for patients with Alzheimer's disease. The agency is set to make a decision by March 7 next year and must choose whether to side with an advisory panel, which voted against approval, or an earlier review by its own staff, which appeared to back clearance of the drug. For further analysis, read ViewPoints: AdCom makes FDA’s job on aducanumab infinitely easier – or more difficult.
Commenting on the tie-up with Sage, Wedbush analyst Laura Chico said Biogen's move into depression treatment was unexpected, "given [its] absence of a meaningful commercial presence in the psychiatry space, but ultimately the company sees this as a good fit for zuranolone." She suggested the move might be a hedge by Biogen against a possible eventual rejection of aducanumab. Meanwhile, Chico thinks SAGE-324 is a good fit for Biogen since some of its main revenue drivers are multiple sclerosis (MS) drugs, and many MS patients experience tremors and spasticity.
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