In a decision contrary to its European counterpart, the U.K.'s Medicines and Healthcare products Regulatory Agency (MHRA) has approved Eisai and Biogen's Alzheimer's disease drug Leqembi—though that's where the positive news for the two pharmas end.
Tuesday, MHRA said it has made Leqembi the first treatment for Alzheimer’s in the U.K. that has shown “some evidence of efficacy” in slowing disease progression. Its green light, however, is for early-stage Alzheimer’s in a patient subgroup that in the U.K. is made up of about 70,000 patients. There are around 1 million patients believed to have dementia in the region.
In clearing Leqembi, the MHRA adopted a similar positive opinion as the U.S. FDA but departed from a rejection by the European Medicines Agency (EMA), which in July ruled that the drug’s effects on delaying cognitive decline do not warrant its safety risks.
However, unlike the FDA, the MHRA has limited the scope of its approval to not allow Leqembi be given to patients with two copies of the ApoE4 gene, citing safety reasons, namely, a higher risk of developing potentially dangerous brain swelling or bleeding known as amyloid-related imaging abnormalities (ARIA). Those ApoE4 homozygous patients constitute about 15% of Alzheimer’s diagnoses, the British agency noted.
Despite the MHRA go-ahead, there's more bad news as patients won't yet have access to Leqembi under Britain’s tax-payer-funded program. In a draft decision, the National Institute for Health and Care Excellence (NICE) denied coverage of Leqembi in the National Health Service (NHS). In a separate statement Thursday, the England drug cost watchdog said Leqembi’s “relatively small benefits” and high costs “means it cannot be considered good value for the taxpayer”
NICE’s guidance is not final and is now open for comments until Sept. 20 with another drug review committee meeting planned for later this year. It’s not uncommon for NICE to reverse its stance upon receiving better pricing offers or new clinical evidence.
The price of Leqembi in the U.K. remains confidential. Eisai has offered a commercial arrangement, but it apparently failed to impress NICE. Besides Leqembi’s own cost, NICE also pointed to the costs of providing the treatment, including infusions in hospital every two weeks and intensive monitoring for side effects.
Eisai is “working collaboratively” with NICE, the Scottish Medicines Consortium and the NHS to make Leqembi available to eligible patients as soon as possible, the company said in a statement Thursday. The Japanese pharma leads Leqembi initiatives globally, while Biogen co-promotes the med in the U.K.
The different opinions adopted by global regulatory agencies reflect the ongoing debate around the use of Leqembi and the emerging new class of anti-amyloid antibodies it represents.
In a large phase 3 trial, Leqembi showed a statistically significant benefit in slowing clinical cognitive decline by 33% compared with placebo at 18 months in the now U.K.-approved patient population, which excludes those with two copies of ApoE4, according to Eisai and Biogen.
In its assessment, NICE interpreted the trial’s finding as Leqembi providing “on average 4 to 6 months slowing in the rate of progression from mild to moderate Alzheimer’s disease,” Helen Knight, director of medicines evaluation at NICE, said in a statement.
“[B]ut this is just not enough benefit to justify the additional cost to the NHS,” Knight added.
For its part, Julian Beach, MHRA’s interim executive director on healthcare quality and access, said the agency will keep Leqembi’s safety “under close review,” highlighting a controlled post-marketing safety study to evaluate the drug in routine clinical practice, particularly around ARIAs, brain hemorrhage and long-term safety.
Leqembi first got an FDA accelerated approval in January 2023, followed by a traditional nod in July 2023. Upon the FDA full nod, the Centers for Medicare & Medicaid Services announced broad coverage for Leqembi.
Nevertheless, launch of the drug remains slow. In the second quarter, Leqembi brought in just $40 million in global sales, including $30 million from the U.S. Besides the U.S., Leqembi has also been approved in China and Japan, among other territories. In Europe, Eisai has said it will challenge the EMA’s negative opinion.
Despite the full FDA approval and Medicare coverage, adoption has been slow because of the need to build an administration infrastructure, Eisai and Biogen said. Besides, doctors have been very careful with who they’re using the medicine on. Northwestern Medicine, for example, has decided not to give Leqembi to patients with two copies of the ApoE4 gene given its greater safety risk of ARIA.