‘Shaking with excitement’: FDA approves NZ-discovered drug for Rett Syndrome | T-10 NEWS

A just-announced decision by United States regulators has made New Zealand science history, with the Food and Drug Administration (FDA) approving this country’s first locally-discovered neurological treatment to make it to market.

Today’s final marketing approval for Trofinetide – marketed as Daybue – also marks the first-ever FDA-approved drug for Rett syndrome, a severe neurological disorder, estimated to affect 350,000 girls and women worldwide.

Symptoms range from loss of speech, mobility and muscle tone to seizures, breathing problems and slowed growth, with near-constant hand movement a common hallmark.

But Trofinetide has shown exciting promise at treating Rett symptoms, potentially improving the quality of life for the girls and their families.

Its story spans back nearly two decades, to the University of Auckland, where researchers were investigating potential chemical candidates for treating traumatic brain injury.

One of those was a peptide “mimic” they designated NNZ-2566, which proved especially difficult to synthesise.

That molecule eventually became the basis for Trofinetide, as it was named by the World Health Organisation (WHO) – and a flagship product of University of Auckland company Neuren Pharmaceuticals.

Later, Neuren partnered with US company Acadia Pharmaceuticals to carry out the expensive phase-3 trials, with Acadia paying US$10m (NZ$16m) for the drug’s exclusive rights in North America as well as royalties on any sales, plus up to US$455m (NZ$741m) in milestone payments.

More than 20 years later, one of the researchers involved in the founding chemistry work, University of Auckland chemist Distinguished Professor Dame Margaret Brimble, was celebrating the announcement.

“I am shaking with excitement but filled with emotion for all the Rett families,” she told the Herald on Sunday.

Daybue – just one of a handful of NZ-discovered drugs to gain FDA approval – is expected to be available in the US as early as next month.

At this point it’s not clear when it will be accessible to Kiwi patients.

Rett NZ national co-ordinator Lady Gillian Deane understood the drug would also need to go through European approval, but said Kiwi families were eagerly awaiting it.

“They can’t believe it,” she said of their reaction to today’s news.

“This is terribly exciting for us – but also for NZ scientists – that we have this wonderful drug.”

Acadia chief executive Steve Davis said the announcement marked an “important milestone” for the Rett community.

“As the first FDA-approved drug for the treatment of Rett syndrome, Daybue now offers the potential to make meaningful differences in the lives of patients and their families who have lacked options to treat the diverse and debilitating array of symptoms caused by Rett syndrome,” Davis said.

International Rett Syndrome Foundation chief executive Melissa Kennedy said the decision made for a historic day.

“Rett syndrome is a complicated, devastating disease that affects not only the individual patient, but whole families,” Kennedy said.

Rett syndrome is caused by errors in a particular gene, MECP2, which is found throughout the human body but has especially important properties for the brain.

In children with the condition, mutations within MECP2 inhibit the formation of a molecule essential to cognitive and motor function.

Trofinetide, meanwhile, is derived from a protein called the human insulin-like growth factor 1 (IGF-1), which naturally occurs in the brain, where it’s broken down into a protein fragment called glypromate, or GPE.

Tronfinetide is essentially a synthetic modified version of GPE, which is known to reduce inflammation in the brain and help with responding to disease and stress.

Pre-clinical studies in rat models confirmed its neuroprotective effects, before later clinical trials conducted in children showed Trofinetide was safe, well-tolerated and brought some improvements in symptoms for Rett syndrome.

Another potential target for Trofinetide is Fragile X syndrome: The most commonly inherited cause of intellectual disability, as well as the most common known cause of autism.

As before with Rett, there are currently no medicines approved for its treatment.

A second neurological drug from Brimble and her team, NNZ-2591, also has big potential and Neuren is developing it for other serious neurological conditions that emerge in early childhood.

It has already gained FDA approval to enter phase 2 clinical trials for the treatment of Phelan-McDermid syndrome, Angelman syndrome, Pitt-Hopkins syndrome and Prader-Willi syndrome.

Rett syndrome: A Kiwi mum’s story

What’s it like to live with Rett syndrome? Auckland mum Kimberley Sullivan shares this story about her five-year-old daughter Macy Hoyes.

“The happiest baby in the world!”

People would stop me in the mall to comment as I pushed around this perfect cherub-looking angel in the buggy. She smiled at strangers, was happy in anyone’s arms, made all the right noises.

She sat and she crawled, at 17 months she got up and walked and never looked back. Where was the red flag? Should we have known then?

On New Year’s Eve 2018 she spoke her first words: “Pooh Bear.” I couldn’t believe my ears – but she was nearly 19 months old by now and it was starting to play on my mind.

From here on she steadily gained expressive and receptive language, she developed a love for monkeys and could spot a monkey a mile away; a toy in a shop window, a tiny picture on the corner of a page in a book.

Her baby brother was born the day after she turned two, she learned his name and used it and “baby” interchangeably.

But soon we noticed she didn’t care about monkeys any more. She didn’t want to sit and read a book.

She didn’t follow simple instructions any more and she didn’t use the dozen or more words she knew.

She cried a lot, she didn’t seek out the company of others, she didn’t notice other children in the room.

What was happening to our happy girl?

Doctors told us it was autism; “sometimes this happens with autism,” they said about the sudden loss of skills.

We had an MRI and EEG to rule out anything like a tumour or growth in her brain.

“Her brain function is completely normal,” the neurologist told me after the MRI. I thought this was a strange choice of words, because anyone who knew Macy could see that she was not the same child she was six months previously, her brain function quite clearly was not normal.

Her finger clicking was becoming more and more like a tic than a stim – she couldn’t stop herself from doing it and she didn’t seem to enjoy it or find any comfort from doing it.

She could no longer eat with any sort of utensil; her right hand was rendered useless by now, taken over with clicking and mouthing only.

Her left hand would accept food, but toys held no purpose and books wouldn’t hold her interest.

By age 3.5 we were offered further investigation in the way of genetic testing. I had found Rett syndrome online and was fully convinced this was what we were dealing with.

Two geneticists told me that it couldn’t be Rett syndrome – girls with Rett syndrome aren’t as mobile as Macy and they wring or clasp their hands together.

Macy’s hands are never together and one also still works, to a certain extent.

Almost a year later we had an appointment confirming what I had thought the whole time.

“Do you feel vindicated?” the paediatrician asked me.

Yes, I do, but it’s not exactly the result we would ever ask for.

It’s 2023 and our girl is now 5.5 years old. She is very talkative, with various and constant consonant sounds and babble, not amounting to words although on some occasions you would swear she was saying “mama mama” or “no no no” in the right context.

She is still completely mobile, she can climb stairs independently when she wants to.

She has come through her very long, very late and tough regression stage and has been calm and delightful (for the most part) since she turned five.

She looks us in the eyes and gives kisses constantly and we treasure this.

We could consider ourselves lucky; we got several months of meaningful chatter from our girl. I have many videos of her using the words we now yearn for.

I know many Rett families don’t get this. Many don’t ever get to see their girls walk.

But what if her hands worked for something other than constantly clicking fingers and hitting herself in the mouth? What if she could find interest in anything else other than the one TV show she has watched constantly for the last 3 years?

What if she could tell us what she wanted or how she was feeling?

A small improvement in just one of those areas would change Macy’s life.

Here in New Zealand, there is a lot of uncertainty for our small community of Rett families, around when, how and if we will be able to access Trofinetide.

An opportunity to improve our girls’ lives in any way is something we are all desperate for as soon as possible.