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TGA approves Luxturna gene therapy

In a historical development for the eye health sector, the Therapeutics Goods Administration (TGA) has approved the country’s first true gene therapy, indicated for a rare form of inherited retinal disease (IRD).

Luxturna, a highly anticipated treatment that’s locally supplied by Novartis, secured Australian regulatory approval on 5 August. It follows in the footsteps of the US and European markets where it was cleared in 2017 and 2018, respectively, and could pave the way for similar therapies for more common forms of inherited eye disease.

The one-time therapy is indicated for the treatment of a small group of patients with IRD caused by pathogenic biallelic RPE65 mutations, who also have sufficient viable retinal cells.

The active substance in Luxturna is voretigene neparvovec which is a modified virus containing a copy of the RPE65 gene. It delivers the non-mutated RPE65 gene to the retina via a subretinal injection to restore vision and improve sight in children and adults.

A TGA spokesperson confirmed to Insight that it is the first approved in-vivo gene therapy, meaning it directly infects cells in the body. The TGA previously approved Kymriah in 2018, a cancer treatment that uses an ex-vivo approach whereby gene manipulation occurs outside the human body.

Patients with mutations in both copies of the RPE65 gene may manifest as either Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP).

Dr Fred Chen, an IRD clinician-researcher at the Lions Eye Institute and the University of Western Australia, said the sector was excited about the approval. Along with other experts in the area, he was on the Advisory Board for Novartis in assisting the Luxturna TGA approval process and the application with the Medical Services Advisory Committee (MSAC) to have the therapy publicly funded.

Dr Fred Chen, from the Lions Eye Institute, helped advise Novartis with its Luxturna TGA approval.

“The implication of the TGA approval of Luxturna is that this is the first of many other retinal gene therapies that we can ultimately offer to our patients with inherited retinal diseases,” he said, adding that there are 10 other gene therapies for more common IRDs in active clinical trials.

“It is important to realise that the first and only retinal gene therapy was conducted by Professor Ian Constable and Elizabeth Rakoczy at Lions Eye Institute many years ago. It is exciting to see that this retinal treatment approach has finally become the standard care.”

Luxturna is not recommended for patients under the age of four. Chen said it was tested in patients between four and 40-years old, but it would stand to offer more benefit to younger patients due to the higher volume of viable retinal cells.

He said it was unlikely Australian patients would have access to the therapy until it is funded by the government. Reports in the US suggest it costs up to US$850,000 (AU$1.18 million) for therapy in both eyes.

“The MSAC approval process will determine how much the state and federal governments chip in. Part of this process is also to determine which Australian cities will become the treatment centre of Luxturna.”

A rare condition

Chen said RPE65 is one of the rarest forms of IRD and can manifest at different ages.

As an indication, he said for LCA patients, RPE65 may represent 5-20% of the cases. LCA is rare, affecting around 1:40,000 newborns. Whereas for the more common early onset (age 1-5 years),  childhood onset (age 6-10 years), adolescent onset (age 11-17 years) recessive RP, RPE65 may only account for 1-5% of total cases.

He said RP as a whole affects around one in 3000, with two thirds of those exhibiting probable recessive inheritance (one in 6000). No more 1% of these recessive cases are due to RPE65 (<1 in 600,000). Chen estimates that in Australia, there may be 1 in a million population who might have this disease.

Other gene therapies for more common types of IRDs are also in the clinical trial phase.


“Currently, most states in Australia have identified a couple of patients each with this condition,” he said.

“The number of patients found depends on how much genetic testing is done. In an ideal world, all patients are tested, but in our experience, most patients have not had genetic testing. In WA we are active in testing our patients through a clinical or research pathway facilitated by the Australian Inherited Retinal Diseases Registry so these patients can be identified.”

More therapies on the horizon

Dr Jonathan Ruddle, lead of the Ocular Genetics Service at The Royal Victorian Eye and Ear Hospital and a Novartis Luxturna advisory board member, anticipated up to 50 Australians could benefit from the therapy once they were identified in through community eyecare services and referred for genetic testing.

He said the TGA approval was a milestone for genetic therapies in general, with ophthalmology leading the way as it often did due to its unique way of administrating such therapies.

“This is a first but there are a couple of other genes in Phase 3 trials overseas that are more common than RPE65 as a cause of retinal inherited disease, and when they reach our shores that’s going to change a lot more lives numerically and will make a lot of difference,” he said.

Other gene therapies for more common types of IRDs than RPE65-associated retinopathy are in Phase 1, 2 or 3 trials include:

  • ABCA4 (Stargardt disease – (one quarter of all IRDs)
  • CNGB3, CNGA3 (both causes achromatopsia)
  • REP1 (Choroideremia, X-linked)
  • RPGR (X-linked RP)
  • PDE6B (Recessive RP)
  • RLBP1 (Retinitis Punctata Albescens)
  • RS1 (X-linked retinoschisis)
  • MYO7A (Type 1B Usher syndrome)
  • CEP290 (Leber congenital amaurosis) – gene editing.







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