Aduhelm and an expensive failure to launch

Biogen’s treatment for Alzheimer’s was initially regarded as a major treatment breakthrough. Now, only three years later, Ben Hargreaves finds that the abortive launch holds lessons across the industry – from interactions with the regulator to how to price a product at launch.

The search for an effective treatment for Alzheimer’s disease has been an ongoing challenge for the pharmaceutical industry. The allure of continuing R&D in the face of repeated clinical trial failures persisted due to the urgency of the medical need. According to the Alzheimer’s Association, approximately one in nine people aged 65 and older has Alzheimer’s, and with a rapidly ageing global population this means there is both a need for treatments and a major commercial interest in supplying them.

Unfortunately, the dream to develop the first meaningful treatment for Alzheimer’s in recent times ended in a nightmare for Biogen. From the beginning, the approval of its Aduhelm (aducanumab) treatment was met with controversy – over the interactions with the FDA, and the advisor committee’s vote against the treatment being ignored. For Biogen, this led to questions over the approval and eventually a lack of coverage of the treatment, leading to low sales. Ultimately, this saw the company announce that it would ‘realign resources’ for its Alzheimer’s portfolio and stop selling Aduhelm. The highly anticipated launch, along with blockbuster expectations, only to achieve sales of just $4.6 million in FY2022, will mark the drug as one of the most expensive drug launch failures ever. More than this, it will be picked apart by the rest of the industry, and Biogen itself, to learn what went wrong.

On the wrong foot

The major barrier that Biogen faced when commercialising the treatment came from convincing health insurance providers and, importantly, the Centers for Medicare and Medicaid Services (CMS) in the US to provide coverage for Aduhelm. For the former organisations, the coverage was limited. For the latter organisation, which is a federal agency providing health insurance to more than 160 million US citizens, it chose to limit reimbursement of Alzheimer’s therapies to those receiving a ‘traditional approval’, not Aduhelm’s accelerated approval. With a limited number of patients eligible to receive Aduhelm, this effectively signalled the death knell for the treatment.

Lee Fleisher, CMS chief medical officer, explained the agency’s decision: “Science, evidence, and stakeholder input led our team of career civil servants and clinicians through this national coverage determination process. There is the potential for promise with this treatment; however, there is not currently enough evidence of demonstrating improved health outcomes to say that it is reasonable and necessary for people with Medicare, which is a key consideration for CMS when making national coverage determinations.”

According to Biogen’s statement on ending the development and commercialisation of Aduhelm, the company began a strategic review in January 2023, which included seeking potential partners or external financing for the treatment. Despite this, Biogen was unable to find any support and instead chose to terminate its licensing agreement with Neurimmune, leading to the rights to aducanumab reverting to the latter company.

Shifting focus

The reality for Biogen is that the treatment could be written off, though with some financial regret, because the company already had a follow-up. Leqembi (lecanemab), developed alongside Eisai, became the first approved treatment that was shown in the clinic to slow disease progression and cognitive and functional decline. FDA approval for the treatment arrived only two years after Aduhelm’s approval and, even without difficulties of coverage, the discontinued treatment would have suffered from its sales being eaten away by the more effective stablemate.

Biogen effectively acknowledged this by stating that it would reprioritise the resources from Aduhelm into Leqembi, as well as developing its other assets targeting Alzheimer’s. By diverting capital towards the rollout of Leqembi, Biogen may be able to navigate some of the challenges facing the new treatment. Uptake of the therapy is expected to be slow, as Leqembi was approved with a black box warning about the risk of side-effects of the treatment that could be life-threatening. However, sales are eventually projected to reach $7.3 billion by 2030, with revenue evenly split between Biogen and Eisai.

On the horizon, there are also potential competitors within the Alzheimer’s space, as Eli Lilly’s donanemab is expected to receive a decision from the FDA in the short-term. The potential treatment has already managed to show the ability to slow the decline of cognitive function and to inhibit clinical progression. Aiding Lilly in any potential drug rollout is the capital the company has generated through type 2 diabetes treatment, and now approved obesity therapy Zepbound (tirzepatide). Should Lilly receive approval for its Alzheimer’s treatment, the race would be on to determine the market leader. Concentrating its finances into a more successful roll-out of Leqembi, then, makes more strategic sense for Biogen.

Lessons learnt

One of the major lessons for the drug development sector was not taken away by a company, but by the regulator. The backlash against the FDA for its role in approving the drug was fierce, particularly in the way it interacted with Biogen during the process. A congressional investigation into the approval revealed some damaging details of the agency’s role. Notably, the report stated that the FDA’s interactions with Biogen were ‘atypical’ and failed to follow its own documentation protocol. Though anecdotal, the agency rejected 19 drugs in 2022, following Aduhelm’s approval, significantly higher than in recent years.

The same report accused Biogen of setting an “unjustifiably high price for Aduhelm,” with a cost set initially at $56,000 per year. After the launch and the failure to generate significant revenue, the company cut the price by half, but this did not cause a significant uptake of the treatment.

A publication after the entire process also noted that the approval had the potential to disrupt public trust in the approval process. The authors concluded: “When provided information about the approval process, survey participants expressed concern about the controversial pathway, supported measures to restrict drug use to those patients most likely to benefit, and were willing to participate in further randomised placebo-controlled trials. The opinions of an informed public, the authors concluded, should be considered when developing policies in response to aducanumab's approval.”

As confidence in the industry is broadly being eroded, the importance of keeping faith in the approval system and the efficacy of treatments is crucial. This is especially true in a disease such as Alzheimer’s, where the number of patients is large and increasing with an ageing population.