Asia-Pacific Roundup: TGA confirms refusal to register Leqembi in Alzheimer’s after appeal

The Therapeutic Goods Administration (TGA) has confirmed its decision not to register Leqembi to treat Alzheimer’s disease in Australia. TGA reiterated its refusal after Eisai asked the agency to reconsider its original rejection.

In October, the agency declined to register Leqembi, an anti-amyloid-beta antibody authorized in markets including the US, for the treatment of patients with mild cognitive impairment related to Alzheimer's and mild Alzheimer's dementia. TGA took 60 days to reconsider the evidence and evaluate additional proposals made by Eisai. The agency initially rejected the application after concluding that the reduction in disease progression compared to placebo was not significant enough to provide a meaningful clinical benefit or outweigh safety risks.

The second rejection was underpinned by slightly different reasoning. TGA said safety and efficacy were satisfactorily established for APOE4 noncarriers, leading the agency to propose limiting the approval to that subpopulation of patients. Eisai said it was not willing to seek a restricted indication.

“TGA proposed a narrow indication that would limit access to only APOE4 noncarriers. This indication would deny approximately two-thirds of all potentially eligible patients access to a treatment that could slow the progression of AD,” said Lynn Kramer, Eisai chief clinical officer.

Eisai believes APOE4 heterozygote carriers should at least also have access to Leqembi because there is a “similar benefit-risk profile to the noncarrier population,” Kramer said. The drugmaker proposed a way to get the drug to APOE4 heterozygote carriers, but TGA found fault with the offer.

“The Applicant proposed that APOE4-heterozygotes should be treated in specialist centres and supervised by physicians with expertise in monitoring for ARIA,” TGA said. “However, after consideration, the Delegate was not satisfied that this wording would be specific enough to support clinicians and address the outstanding safety concerns for patients who are APOE4 heterozygous carriers.”

ARIA, an acronym for amyloid-related imaging abnormalities, is a side effect associated with Alzheimer’s drugs, including Leqembi. TGA found efficacy is satisfactorily established for APOE4 heterozygous carriers, but occurrences of ARIA and cerebral hemorrhage in that population meant safety had not been shown to its satisfaction.

TGA’s decision to confirm the initial decision not to register the drug is reviewable by the Administrative Review Tribunal. Eisai said in a statement that it “remains committed to ensuring eligible Australians with early Alzheimer’s disease can access lecanemab,” the active ingredient in Leqembi, and is exploring options, including potentially seeking review by the Administrative Review Tribunal.

TGA Notice, Eisai Statement

Philippine FDA meets with drug manufacturers to discuss path to PIC/S membership

The Philippine Food and Drug Administration (FDA) has met with manufacturers to discuss the path to Pharmaceutical Inspection Co-operation Scheme (PIC/S) membership.

FDA applied for PIC/S membership in August 2023. Recently, the agency met with industry associations and stakeholders in the human and veterinary medicinal products sectors to provide updates on efforts to join PIC/S and the role that manufacturers can play.

The agency encouraged manufacturers to align with PIC/S guidelines, arguing that it “would not only enhance their market authorization opportunities but also provide a competitive edge in the global pharmaceutical industry.”

Accession to PIC/S takes six years. One reason for the length of the process is to give national industries enough time to comply with the PIC/S GMP Guide. Applicants also use the time to make internal improvements, such as changes to their quality systems and training of inspectors.

The recent meeting allowed stakeholders “to raise concerns and receive direct responses from FDA officials, ensuring clarity on regulatory expectations,” the agency said. To strengthen collaboration with industry, the FDA proposed holding monthly consultations, with dedicated sessions for human and veterinary drug manufacturers.

Press Release

DRAP responds to WHO concerns about pharmacovigilance centers

The Drug Regulatory Authority of Pakistan (DRAP) has outlined the actions the country will take in response to the identification of concerns with the rollout of its pharmacovigilance activities.

In November, the World Health Organization (WHO) held the second review meeting related to DRAP’s implementation of a pharmacovigilance system. At a recent meeting, DRAP's Pharmacovigilance Risk Assessment Expert Committee said WHO voiced concerns “about the non-establishment of Pharmacovigilance Centres, notification of committees in all provinces and harmonization of procedures and tools. "

The committee proposed a series of steps to address the concerns. Provincial health departments and pharmacovigilance centers should “take all necessary measures for the implementation of the road map that was agreed by provinces and DRAP for earlier implementation of WHO Institutional Development Plans to strengthen the National Regulatory System of Pakistan,” the committee said.

Two provinces, Balochistan and Sindh, were told to “notify their Provincial Pharmacovigilance Centres and share details of the Provincial Focal Person and pharmacovigilance officers from hospitals for the VigiFlow logins.” DRAP will coordinate with the provinces on the activities. Other steps include extending the scope of the VigiFlow database to all public and private hospitals.

Meeting Minutes

Singapore’s HSA alerts patients to risks of using smartphones for critical diabetes alerts

Singapore’s Health Sciences Authority (HSA) has warned patients of potential risks associated with using smartphones to receive critical alerts from diabetes devices.

Devices, including continuous glucose monitors, insulin pumps, and automated insulin dosing systems, use smartphones to communicate critical information to patients. Overseas, patients have suffered harm, including low and high blood sugar, diabetic ketoacidosis, and death because smartphone alerts have not been delivered or heard.

HSA has not received any reports of such problems in Singapore but has responded to the issues seen overseas. The agency outlined the conditions that can stop patients from seeing alerts, such as the use of “do not disturb” settings, apps entering deep sleep after an extended period of non-use, and the volume level changing when the smartphone connects to wireless earphones or car audio systems.

The agency has asked patients and caregivers to verify that mobile applications are configured according to the manufacturer’s instructions. If application alerts are not working as expected, users should contact their device’s technical support.

HSA Notice

TGA strengthens warnings about serious side effects linked to broad-spectrum antibiotics

TGA has strengthened the warnings for broad-spectrum antibiotics to communicate concerns about the risk of disabling and potentially irreversible adverse events.

The updates apply to oral and injectable formulations of the fluoroquinolones ciprofloxacin, norfloxacin and moxifloxacin. The labels of the broad-spectrum antibiotics already carried warnings about the risk of tremors, restlessness, light-headedness, hallucinations, seizures, inflamed and ruptured tendons and psychiatric reactions such as confusion, anxiety and depression.

TGA has strengthened the warnings about adverse events by making the information more prominent on the product information and consumer medicine information. The side effects can affect people of any age without pre-existing risk factors and have been reported simultaneously in the same patient. The nervous system and psychiatric reactions can occur after the first dose.

The Australian regulator took the actions after its UK counterpart found warnings applied in 2019 had not appeared to reduce prescribing rates by 2023. The UK agency recommended updates to the safety information to highlight the risks of the side effects.

TGA Notice, More

Asia-Pacific Roundup: TGA confirms refusal to register Leqembi in Alzheimer’s after appeal

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