With an increasingly aging global population, neurological disorders have become a major cause of death and disability worldwide. Despite the significant investments that continue to be made in research and development in the neurological field, the discovery of new drugs targeting many CNS disorders, including Alzheimer’s and Parkinson’s diseases, has proved to be difficult. Often the share values of companies in that area can exhibit wild swings related to success or failure in clinical trials.
In addition, the COVID-19 pandemic is requiring companies to readjust their clinical trial schedules and programs. These pressures have weighed on members of the BioWorld Neurological Diseases index, which has slipped about 4% in value so far this year. (See BioWorld Neurological Diseases index, below.)
Adjusting to COVID-19 realities
Cambridge, Mass.-based Sage Therapeutics Inc.’s shares (NASDAQ: SAGE) have tumbled 48% this year. In its first-quarter financial results, the company reported that its 60-hour intravenous (I.V.) Zulresso (brexanolone) to treat postpartum depression (PPD) sales were impacted by COVID-19.
The company revealed a significant reduction in patient demand as well as sites of care starting to pause treatment of new patients with the drug during March, and in increasing numbers since then. As a result of the pandemic, only approximately 15% of sites active in the first quarter remained active in April. “Concerns about exposure to the virus have also caused a reduction in the number of women with PPD seeking treatment with Zulresso, as evidenced by the approximately 75% decline in the monthly start form volume in April compared to the average monthly volume for the first quarter of 2020,” the company reported.
As a result of that evolving situation, the company undertook a corporate restructuring, reducing its workforce by 53%; that included the elimination of its entire sales force.
“We believe this cost reduction and reallocation of resources will help Sage advance our portfolio in a way that is consistent with our mission of delivering medicines that matter to people with serious brain health disorders,” noted company CEO Jeff Jonas.
The company also reported that the rest of its pipeline has remained unaffected by the pandemic so far and it will continue to focus on its three brain health franchises – depression, neurology and neuropsychiatry, with anticipated 2020 and 2021 R&D milestones remaining unchanged.
Clinical trial disappointment
Prothena Corp. plc, a clinical-stage neuroscience company with expertise in protein misfolding, has several partnered programs, including prasinezumab (PRX-002/RG-7935), in collaboration with Roche Holding AG for the potential treatment of Parkinson’s disease and other related synucleinopathies, and programs that target tau, and an undisclosed target in collaboration with Bristol-Myers Squibb Co. for the potential treatment of Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) or other neurodegenerative diseases. Since the beginning of the year, the company’s share value (NASDAQ:PRTA) has dipped about 40%. A clinical trial disappointment for prasinezumab was one of the contributing factors, with Roche reporting in its Q1 earnings that the phase II Pasadena study of the compound in patients with early Parkinson’s disease did not meet the primary objective, though it showed signals of efficacy. Those signals were observed on multiple prespecified secondary and exploratory clinical endpoints. Roche said it has begun further clinical development planning activities and is evaluating the data to determine next steps.
Taking a pause
South San Francisco-based Denali Therapeutics Inc. has enjoyed a positive year so far, with its share value (NASDAQ:DNLI) increasing by approximately 47%. The company, which is developing a portfolio of product candidates engineered to cross the blood-brain barrier for neurodegenerative diseases, said, together with partner Paris-based Sanofi SA, it will pause its clinical studies of DNL-747 in Alzheimer’s disease and amyotrophic lateral sclerosis and concentrate on developing DNL-788, a small molecule the company said has a more rapid path toward proof-of-concept clinical studies in patients in multiple neurological indications. Chronic toxicity studies with DNL-747 in cynomolgus monkeys showed dose- and duration-dependent adverse preclinical findings at exposures higher than those tested in the clinic, the company said. Those findings, considered off-target and molecule-specific, impact the ability to increase the dose of DNL-747 and achieve higher levels of target inhibition without time-consuming additional clinical safety studies in patients to evaluate the long-term safety and tolerability, the company concluded.
New Haven, Conn.-based Biohaven Pharmaceutical Holding Co. Ltd. has seen its shares (NASDAQ:BHVN) rise almost 26% this year. Early in April, the company reported that it is collaborating with Cove, a company providing specialized care and access to innovative treatments for migraine sufferers via telemedicine services in the U.S. The arrangement will allow telemedicine evaluation for migraine sufferers during those times of limited access to routine office visits. Using Cove, patients consult with independent health care providers and may be prescribed the company’s recently FDA-approved Nurtec ODT (rimegepant), a calcitonin gene-related peptide receptor antagonist, along with other migraine treatments. The company has also put in place an agreement with Medison Pharma Ltd., of Petach Tikva, Israel, to distribute Nurtec ODT in Israel.
In Mizuho Securities’ weekly prescription tracker of biopharmaceuticals, they reported Nurtec ODT is one of two key products they are watching in the acute migraine treatment market, together with Abbvie Inc.'s Ubrelvy (ubrogepant). The firm has a “bullish view on the space and on the uptake of these novel agents.”