Biogen has responded to questions from the Alzheimer’s disease community regarding its Eisai-partnered anti-amyloid drug Aduhelm, as recently revealed memos show a struggle within the US Food and Drug Administration (FDA) over the drug’s approval.

In an update, Biogen and Eisai said that they were ‘committed’ to responding to questions from the Alzheimer’s community and the companies shared some new information on the status of a confirmatory trial, the results of which will determine the continued approval of Aduhelm (aducanumab) as a treatment for Alzheimer’s disease.

The companies said they were ‘urgently’ working to put resources and plans in place to ensure the completion of the confirmatory trial ahead of the nine-year time frame.

This includes advancing the design of the trial protocol, with Biogen and Eisai adding that they plan to engage with regulators, investigators and other stakeholders as they move forward towards patient enrolment.

The update comes after memos were recently revealed from the FDA, showing that there was an internal struggle over the approval of Aduhelm earlier in June.

The memos, according to Reuters, shows disagreements within the FDA over whether to approve Aduhelm using the accelerated approval pathway or a regular approval pathway.

Ultimately, the FDA granted Aduhelm an accelerated approval, meaning that a confirmatory study is needed to ensure the drug can continue to be used to treat certain Alzheimer’s disease patients.

The US Food and Drug Administration (FDA) has granted Eli Lilly’s investigational Alzheimer’s disease drug donanemab a breakthrough therapy designation (BTD).

The BTD is based on data from the phase 2 TRAILBLAZER-ALZ study – the results of which were revealed earlier this year.

Top-line data from the TRAILBLAZER-ALZ trial in patients with early symptomatic Alzheimer’s showed that donanemab slowed cognitive decline by 32% on the Integrated Alzheimer’s Disease Rating Scale (iARDS) compared to placebo.

Following this, Lilly reported that although secondary outcomes within this trial ‘showed no substantial difference’, exploratory analyses showed donanemab slowed the accumulation of tau across key brain regions in Alzheimer’s patients.

In addition, 40% of donanemab-treated patients achieved amyloid negativity as early as six months after starting treatment and 68% achieved this target by 18 months.
In a statement, Lilly said that it intends to submit a biological licence application (BLA) for donanemab under the accelerated approval pathway later this year, based on data from the TRAILBLAZER-ALZ study.

Lilly is also evaluating donanemab in a phase 3 trial – TRAILBLAZER-ALZ-2 – which is set to enrol 1,000 participants in a bid to confirm the efficacy and safety of donanemab in a larger population of Alzheimer’s patients.

Anavex Life Sciences’ investigational drug candidate ANAVEX2-73 led to improvements in clinical efficacy endpoints, including cognitive and non-cognitive measures, in a phase 2 Parkinson’s disease study.

The phase 2 trial enrolled 132 patients with Parkinson’s disease, with candidates randomised equally to receive either 30 mg, 50 mg ANAVEX2-73 or placebo, respectively.

The study found that the treatment resulted in a significant increase in mRNA expression of the SIGMAR1 (sigma-1 receptor) – the drug’s target biomarker.
Previous data suggests that activation of SIGMAR1 can lead to the restoration of complete housekeeping function in the body, and is key to restoring neural cell homeostasis and promoting neuroplasticity.

Independent research also strengthens the case that SIGMAR1 activation has a beneficial effect as a compensatory mechanism to chronic central nervous system (CNS) diseases.

ANAVEX2-73 is designed to activate SIGMAR1 and is also in development as a treatment for Alzheimer’s disease, Rett syndrome, infantile spasms, Angelman’s syndrome and Fragile X syndrome.

In the phase 2 trial, the boost of SIGMAR1 observed with ANAVEX2-73 treatment correlated with clinical efficacy, showing statistically significant improvements compared to placebo on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score.

The MDS-UPDRS total score improved by 10.98 points in the high-dose ANAVEX2-73 group, while it worsened by 3.53 points in the placebo group from baseline to the end of the trial at 14 weeks.