No Playbook For Leqembi: Eisai's Long Game In Alzheimer's Disease
By Ben Comer, Chief Editor, Life Science Leader
The FDA’s full approval of Leqembi in July of 2023, following an Accelerated Approval in January 2023, marked a turning point in the treatment of Alzheimer’s disease (AD). The FDA’s full or traditional approval of Leqembi was based on the Phase 3 Clarity AD clinical trial, which established safety and efficacy. In 2023, the cost of caring for AD and other dementia patients in the U.S. was $345 billion, including $87 billion in out-of-pocket payments, $147 billion in Medicare payments, and $65 billion in Medicaid payments, according to the Alzheimer’s Association.
AD kills more people than breast and prostate cancers combined. To address the societal burden and the sheer cost of caring for patients, full regulatory approval of a safe and effective, disease-modifying drug for AD is indispensable. In addition to the patient and caregiver benefits Leqembi can deliver, the approval served as an important catalyst for other AD drug developers – and their investors – which will benefit from the Leqembi example; assuming Eisai, the company responsible for crafting and leading the Leqembi launch, including pricing and patient access, can deliver a commercial success.
For insight into Eisai’s Leqembi commercialization strategy –from publishing a price and “societal value” assessment, to overcoming payer access hurdles, building a patient support program, and launching physician and consumer education and marketing materials – Life Science Leader spoke with Eisai’s Paul Hawthorne, EVP, purpose and chief business officer. Hawthorne joined Eisai in 2016; before that, he worked in several commercial leadership roles over 23 years at Sanofi. “The tremendous hope that Leqembi is bringing to patients, families, and healthcare professionals is special, and entirely unique to anything I have experienced in my career,” says Hawthorne. Successfully commercializing Leqembi is a chance to give AD patients “more tomorrows like yesterday.”
Moving Forward After Aduhelm
Aduhlem, Biogen and Eisai’s first partnered AD therapy, which also targeted amyloid in the brain, failed commercially. After receiving Accelerated Approval in June 2021 – a first for a drug targeting the causes, versus treating the symptoms, of AD – CMS determined that it would not cover the drug for Medicare patients until the companies could produce more evidence for improved patient health outcomes, not just amyloid removal. For a little while, the drug seemed on the verge of sinking the amyloid hypothesis entirely, even as Aduhelm clinical research pressed on. Leqembi’s full approval, however, and the strength of its CLARITY AD Phase 3 study on patient outcomes, will no doubt hasten further research and bring new investors, and new drug candidates, into neurogenerative disease development programs.
Aduhelm’s controversial approval and ultimate demise had a similar effect in fostering renewed interest in AD drug development, but it also eroded the trust of some patients and providers, an outcome Eisai is keen to avoid with Leqembi. In some ways, that outcome is Eisai’s to win or lose; with Aduhelm, Biogen worked as the lead development and commercialization partner. With Leqembi, the roles are reversed: Eisai leads the launch and commercialization effort and is also the lead development partner.
Eisai set Leqembi’s drug price at $26,500 per year, and took the unusual step of showing its work in selecting that price. Hawthorne notes that Eisai did not participate in Aduhelm pricing decisions, and that “companies have gotten in trouble for not being transparent about pricing strategies.” Given the amount of attention placed on Leqembi’s launch and price, and with the Aduhelm experience factored in, “we wanted to make sure that we are clear about the value a product like Leqembi could bring to society, and how we are willing to share in that value,” says Hawthorne.
Did it work? Although the Institute for Clinical and Economic Review (ICER), a third party drug value assessment group, determined that Leqembi’s price should be lowered from $26,500 to between $8,900 and $21,500 per year to meet “common thresholds for cost-effectiveness,” the market response was positive. “It is easy to get hung up on initial list price,” says Hawthorne. “But it’s really important to look at the long-term cost savings, and we were able to spell that out.”
Shortly after Leqembi’s full approval, which appears to have moderated initial access concerns, CMS announced broader coverage for patients in Medicare, and last October, the agency expanded coverage for PET imaging used to diagnose AD or confirm amyloid plaque; Hawthorne says that all 12 Medicare Administrative Contractors, or MACs, have been adjudicating claims for several months now. Roughly 75% of the traditional Medicare and Medicare Advantage population most relevant to Leqembi’s clinical profile is now covered, as well as “close to 70%” of the relevant commercially-insured population, says Hawthorne. Medicaid plans in all 50 states are covering Leqembi, and “we now have [pharmacy and therapeutic committee] formulary approvals with 73 of the top 100 IDNs,” or integrated delivery networks, in the country, adds Hawthorne. “These things don’t happen overnight.”
Writing The Playbook
Before Leqembi, which is administered by intravenous infusion once every two weeks, there was no established marketplace for a disease-modifying therapy in AD. Additionally, Medicare coverage requires not only a mild AD diagnosis, but also documented evidence (often in the form of a PET scan) of amyloid plaque, as well as a treating physician “who participates in a qualifying registry with an appropriate clinical team and follow-up care,” according to CMS coverage guidelines. Because of the limited treatment options previously available to AD patients, “our healthcare systems did not have the infrastructure already established to immediately begin treating patients,” says Hawthorne.
In most cases, healthcare systems can easily adopt an oncology drug, for example, following FDA approval, even an Accelerated Approval. With the Leqembi launch, by comparison, most health systems decided to wait until Medicare announced broader coverage following full approval, before investing the time and resources needed to administer the drug. These factors contributed to an initially slow start in market uptake, but healthcare providers are now hustling to make the changes necessary to deliver the drug to patients, says Hawthorne.
The challenge of building a new market from scratch comes with opportunities, as well; it gives Eisai a chance to “play a unique and even more meaningful role in helping to establish an infrastructure,” and to provide educational resources to healthcare professionals, and to simplify the treatment journey for patients, says Hawthorne. For example, the company created the Eisai Patient Support program, which includes Leqembi “patient navigators” that provide information about getting access to Leqembi, helping patients and families understand insurance coverage and options, and to identify financial support programs and eligibility.
On the professional sales and marketing side, Eisai is focused initially on neurologists, including neurologists in community practices, infusion centers, IDNs, as well as payers, to “ensure they all have the information needed to initiate and reimburse treatment for appropriate patients,” Hawthorne says. A broad set of personnel across commercial, medical affairs, and market access functions have been deployed, but importantly, Eisai made sure that “a single point of contact exists for all healthcare professionals, so that we can focus our efforts and simplify things to the extent possible for clinicians.”
The time has not yet come for a consumer marketing and DTC advertising effort; Hawthorne says the company is focused on educating patients and families already in the process of diagnosis and treatment. “We want to ensure that we don’t overwhelm a system that is not yet ready … we are evaluating the timing of a more substantial DTC effort, which we plan to deploy in the future on a market-by-market basis, based on readiness,” he says. On the other hand, “various indicators related to market readiness” have progressed enough to warrant an increase in the number of field-based resources to better serve healthcare professionals, says Hawthorne.
Aside from the two leading access challenges of helping patients navigate an unstructured (and at times wildly confusing) healthcare system in the U.S., and advancing healthcare system readiness, Hawthorne says a third key challenge is that patients, especially in certain areas of the country, struggle with timely access to a neurologist. “This problem will resolve in many ways over time,” says Hawthorne. “We are regularly encouraged by stories of physicians who are reconfiguring their practices, hiring additional staff, and adding infusion chairs to create near-term capacity for greater patient care.”
Taking The Longer View
The AD drug development landscape is littered with failures, a fact that led many companies to seek their fortunes in different therapeutic areas, and different indications. Eisai took a different approach, says Hawthorne. It stayed the course. Haruo Naito, Eisai’s CEO, director, and representative corporate officer, joined the company in 1975 and became CEO in 2003 – he is a descendent of Toyoji Naito, Eisai’s original founder. CEOs at many large, publicly-traded companies typically last somewhere between five and seven years in the role, says Hawthorne. CEOs at Eisai, by contrast, tend to stay in the role much longer, which allows the organization to focus more on the future. “We’ve been in Alzheimer’s for four decades now, and CEO Naito has remained focused, persistent, and resilient,” says Hawthorne, noting that Naito was “head of the labs at the time when Eisai developed and commercialized Aricept,” an AD therapy first approved in 1996.
Asked about Leqembi goals for 2024, Hawthorne says Eisai aims to achieve steady market penetration and growth through the further establishment of the diagnostic and treatment pathway. That growth can help to lift the boats of other businesses working in AD drug development, but also ancillary or connected businesses, such as diagnostics. “You’re now seeing mobile MRIs, and mobile PET systems being put in place,” says Hawthorne. Once a new therapeutic market is established, and especially after the first product in that market makes it across the finish line, a significant amount of investment can be expected to flow into the area. “I think we’re seeing that now,” says Hawthorne.
Industry analysts are watching to see how much progress Leqembi makes before the FDA approves, potentially, a close competitor in Eli Lilly’s donanemab. That FDA decision is expected this quarter; donanemab is also infused, but only once a month, instead of Leqembi’s once every two weeks administration. However, Eisai plans to file a BLA for a Leqembi subcutaneous formulation by the end of March, opening the door to self-injection at home. For relevant AD patient populations, these new disease-modifying therapies can’t arrive fast enough.