The US Food and Drug Administration’s landmark but controversial approval of a new treatment for Alzheimer’s disease suggests a sea change in the regulator’s attitude to green-lighting novel drugs for difficult-to-treat illnesses, according to Australian late-stage drug developers.

The powerful FDA this week granted ‘accelerated approval’ status to a drug called aducanumab, developed by the Nasdaq-listed Biogen, under the brand name Aduhelm.

The first new Alzheimer’s drug in 18 years, Aduhelm is claimed to reduce amyloid beta plaques in the brain, which are a biomarker of the disease.

The approval was based on the results of three trials enrolling 3482 patients. Two of these studies were halted in 2019 after the results showed little or no benefit, but the trial custodians later determined a 22 per cent reduction in the rate of cognitive decline among a highly-dosed cohort.

An FDA expert committee recommended against approving the drug and the agency notes “residual uncertainties regarding clinical benefit.”

The nexus between amyloid build up and Alzheimer’s progression is also disputed in the medical community. As a safety net, the FDA requires Biogen to undertake a confirmatory trial and it can revoke approval if a clinical benefit is not proven.

But the broader message is that the agency was willing to approve the drug on imperfect data. And rather than limiting the approval to early onset patients the agency has left it to doctors and insurers to determine the usage of the $US56,000 ($72,000) a year drug.

Few drugs in difficult diseases such as Alzheimer’s are truly curative and Aduhelm is no exception, says Dr James Garner, CEO of Kazia Therapeutics (ASX:KZA).

“However the FDA is increasingly willing to approve drugs which provide modest but material incremental benefit to patients, recognising in effect, that the journey of a thousand miles begins with a single step.”

He says the approval shows the FDA is willing to find “novel pathways” to get drugs for high-need indications to market.

“That has positive implications for drug developers working in areas such as cancer, genetic diseases and neurodegenerative diseases, which are very poorly served by existing therapies.”

Kazia is striving for a treatment for glioblastama (brain cancer), which is another challenging disease with few treatment options.

“Our program is already optimised to generate opportunities for early approval, so we don’t envisage any significant change in strategy,” Garner says. “But the Aduhelm approval provides a great deal of reassurance that any positive data will be valuable in our discussions with FDA.”

A prominent US physician and consultant to Antisense Therapeutics (ASX:ANP), Dr Gil Price notes the FDA’s approval was based on complex data set. That being the case, Biogen will conduct a controlled trial for the verification of Aduhelm clinical benefit in patients with AD.

“But if Antisense Therapeutics produces similar data, we would expect a similar decision from FDA,” says Price, a former director of the Nasdaq-listed Duchenne muscular dystrophy (DMD) drug developer Sarepta Therapeutics.

Antisense is is planning to pursue FDA “fast track” designation for its DMD drug candidate ATL1102. DMD is an incurable muscle wasting disorder that affects one in every 3600 to 6000 male children.

The company is currently discussing the construct of a proposed phase 2b/3 trial with the FDA.

However Price says the FDA’s decision does not constitute a lowering of standards.  “The FDA reviewed data in a very difficult therapeutic area, and made a reasonable decision that offers patients hope,” he says.

“Keep in mind that FDA has been working with Biogen over the past 10 years as a partner, more than an overseer.

“Antisense Therapeutics appreciates the culture at FDA for the development of drugs that treat rare diseases and hopes to build a similar relationship as we continue to move forward.”

Ostensibly, the Aduhelm approval bodes has direct relevance for the ASX listed Actinogen (ASX:ACW), which has just received clearance for a local clinical trial of healthy volunteers and Alzheimer’s patients with mild cognitive impairment.

Actinogen’s lead drug, Xanamem, pursues a different mechanism of action to Aduhelm, by inhibiting the brain enzyme that makes the stress hormone cortisol.

Actinogen CEO Dr Stephen Gourlay believes the FDA’s decision does not so much lower the bar, but it “enshrines” the agency’s already low acceptance criteria for drugs targeting hard-to-treat indications.

Gourlay believes the FDA made a “reasonable and balanced” decision to approve the drug conditionally for such a difficult disease (bearing in mind the requirement for a confirmatory trial).

He says the FDA took the view the negative Aduhelm trial was heavily influenced by a small number of patients with rapid progression of the disease, which may have skewed the result.

“All of that said, the efficacy levels in the approval are relatively modest and there are some safety issues associated with the drug.”

Actinogen shares have more than doubled in the last month – but the direct reaction to the Biogen news was muted.

However there was less reticence among investors in Cogstate (ASX:CGS), which has developed cognitive tests for concussion and for use in clinical in areas including Alzheimer’s (a subset of dementia).

Cogstate is partnered with Japanese neurology house Eisai Co, which in turn has been is partnered with Biogen since 2017.

In a ten-year deal inked last October, Cogstate granted Eisai the exclusive rights to develop and distribute Cogstate’s digital cognitive assessment tools globally.

“It is expected that such [tools] will play an important role in supporting the type of large scale cognitive assessment that will be necessary in the launch of disease modifying therapies, such as Aduhelm,” Cogstate says.

But there’s a more specific reason for Cogstate’s 59 per cent share surge in response to the news.

The approval means that as well as paying Cogstate contracted minimum royalties of $US10 million in the first five years, it is now obliged to pay an additional $US20 million over the next six to ten years.

Cogstate also received an $US15 million upfront royalty in December 2020.

Meanwhile, the FDA decision sends the right vibes to immunotherapy play Immutep (ASX:IMM), which is pursuing novel therapies for cancer and autoimmune diseases.

Immutep recently won FDA fast track approval status for first-line use of its drug candidate Efti for head and neck squamous cell cancers. The company also has FDA approval to pursue late-stage trials for metastatic breast cancer.

The FDA’s apparent attitudinal shift is also relevant for stem-cell therapy developer Mesoblast (ASX:MSB), as it prepares to re-submit an approval application for its graft-versus-host disease treatment Remestemcel-L

In a reverse of the Biogen experience, an FDA expert committee last year voted nine-to-one in favour of approving the application, but the agency itself knocked back the entreaty for want of deeper clinical evidence.

The Aduhelm ruling raises hopes that the FDA will take a more accommodative view this time around.

But whether the FDA decision represents a lowering the bar or not, what’s less disputable is that it shows the agency recognises that a ‘one size fits all’ approach is no longer appropriate.

“In other words rarer and difficult diseases such as Alzheimer’s and brain cancer have to be treated to, say, hair loss or acne,” Kazia’s Garner says.

“A more bespoke, less procedural, approach to drug approvals is ultimately in everyone’s best interests.”