Another year has ended, and a new one has begun. We hope that 2022 was a successful one for you, and wish you an even happier, healthier and more prosperous 2023! It is a time-honored tradition at the start of the new year to consider what may lie ahead in the months to come. So, to begin our posts for 2023, here are a few areas we will be watching as the year progresses:
- Positive Developments in Alzheimer’s Disease
Late 2022 saw the first advance in Alzheimer’s disease (AD) drug development in many years, and—to the surprise of some —a strengthening of the hypothesis that amyloid plaque deposition in the brain is a driving force in this condition. Eisai and Biogen showed in a Phase 3 trial that lecanemab, their 2nd anti-amyloid antibody, both reduced amyloid plaque in the brains of people with early-stage disease and slowed decline in cognitive function, albeit modestly but with statistical significance. A number of questions are yet to be answered on what, if anything, this small win might mean to patients’ lives and for issues concerning pricing, reimbursement and access. However, the FDA granted accelerated approval to lecanemab on January 6, as expected, and the drug will be marketed as Leqembi. We are going to comment on lecanemab’s development in greater depth—as well as prospects for a few other drugs that aim to treat AD through different pathways—in two upcoming posts.
We will also be watching for other interesting scientific developments in the AD research field, notably a gene therapy approach to treating individuals who carry two copies of the APOE4 gene variant, which causes a lifetime risk of developing AD of 30% to 55%. Preliminary results from a clinical safety study in which five patients were treated with a low dose of APOE2 (a variant of the APOE gene associated with reduced risk of AD) showed a fall in gene expression in the patients’ spinal fluid, and brain levels of amyloid and tau, a second protein marker of AD. The researchers hope that expression of APOE2 in the brain will change the profile of someone with two APOE4 variants to one that resembles a person with one each of APOE4 and APOE2, which could potentially cut their risk of AD in half. Treatment of another five individuals at a higher dose of the gene therapy is now underway, and we will look forward to hearing about those results.
- Wins in Other Hard-to-Treat Diseases
AD is not the only hard-to-treat disease where we are starting to see wins. We will be watching for positive news in two other conditions: non-alcoholic steatohepatitis (NASH) and depression.
NASH, a leading cause of liver-related mortality, presents an increased risk for heart attack and stroke, and is a growing burden on global health care costs. No approved drug therapies exist for the condition, with liver transplantation as the only available treatment, and a series of disappointing trial results have stymied innovation in the field. In late December 2022, however, Madrigal Pharmaceuticals announced positive topline results from its pivotal Phase 3 study of resmetirom, the company’s liver-directed selective thyroid hormone receptor agonist. Madrigal plans to use these results to file for accelerated approval in the first half of 2023, while continuing that study and three additional Phase 3 trials to evaluate resmeritrom’s long-term efficacy. On December 21, 2022, Madrigal announced they had raised $300 million to support this clinical development program and planned commercial activities for the accelerated approval of the drug.
Major depressive disorder is a difficult disease to treat, but it is also an area where we are starting to see some advances. We expect positive news to continue, and we will be particularly watching for the potential approval and launch of zuranolone, which holds Fast-Track and Breakthrough Therapy designations. The result of a development partnership between Biogen and Sage Therapeutics, zuranolone’s New Drug Application was submitted to the FDA in early December 2022. Zuralone is an oral, once-daily, rapid-acting 14-day treatment for major depressive disorder and postpartum depression. A PDUFA date has not yet been announced, but Sage expects it to be in Q3 2023.
- More M&A and Corporate Strategic Changes
2022 was a relatively quiet year on the mergers and acquisitions front, but we will be watching for such activities to pick up again in 2023, as global consultants PricewaterhouseCoopers (PwC) and others have predicted. PwC cites the reasons as strong company balance sheets, ample corporate cash on hand for acquisitions, rich availability of great late-stage science, and multiple companies seeking to augment their pipelines as older products approach patent cliffs.
We saw some notable C-suite changes in late 2022, which could herald changes of strategic direction at some companies in 2023. At Biogen, for example, Christopher A. Viehbacher—whose background includes six years as global CEO at Sanofi and 20 years at GlaxoSmithKline—replaced Michel Vounatsos in November 2022, as Biogen prepares to focus on a potential lecanemab launch. There may also be changes in store at Roche, following the departure of pharma CEO Bill Anderson at the end of 2022. Filling Anderson’s role will be a major near-term priority for the company, as Roche prepares to launch Lunsumio (mosunetuzumab-axgb), following its late-December 2022 approval in follicular lymphoma, and looks forward to read-outs from 15+ Phase 3 trials in 2023.