• Orphan diseases are those impacting less than 200,000 patients
  • Orphan drug designation ensures an exclusivity period for pharma companies
  • The average orphan drug in the US retails for US$7,000 per month


Rare or ‘Orphan’ diseases affect a small number of people globally, defined as less than 200,000 in the US and 10,000 in Australia.

Normally these conditions would be uneconomical to treat due to the limited market, because pharmaceutical companies would be concerned they’d be unlikely to recover their development and marketing costs – let alone profit.

That’s where Orphan Drug Designation (ODD) comes in. It’s a financial incentive for pharmaceutical companies to develop and treat these rare diseases.

The benefits differ between different jurisdictions but typically include tax credits, market exclusivity for several years after approval (seven in the US, 10 in the UK and Europe – but we’ll get to that later) and waiver of drug application fees.


Orphan drug pricing the key to profitability 

One company taking advantage of Orphan Drug Designation is Dimerix (ASX:DXB) in its Phase 3 clinical trial in Focal Segmental Glomerulosclerosis, a rare disease of the kidneys which affects children as young as two years old, as well as adults. It causes inflammation and irreversible scarring, leading to permanent kidney damage and eventual end-stage kidney failure requiring dialysis or transplantation.

DXB has secured Orphan Drug Designation in the US and in Europe for its DMX-200 drug drug. 

To put that in context, in the US, the average orphan drug retails for around US$7,000 per month or US$84,000 per year. 

CEO and MD Dr Nina Webster says this pricing is a vital incentive for pharmaceutical companies who are going to the expense of developing a product for a small patient population.

“A standard branded drug in the US is probably a fraction of orphan drug pricing, around US$500 per month, so you’ve got US$500 per month per patient versus US$7,000 per month per patient,” she said.

“Orphan drug pricing in the US is obviously more expensive than Europe, but both are very lucrative. 

“If the average US branded product is US$500 per month, in Europe it’s about 10% of that, which is same as Australia, at around US$50. 

“But orphan in Europe is around 50% of US, so if it was US$7000 in the US, it’ll be about €3500 in Europe – which is a really attractive opportunity.” 


Price per patient per month in the thousands 

One example Dr Webster points to is Neuren Pharmaceuticals (ASX:NEU), whose DAYBUE (trofinetide) drug was approved by the US FDA in March and is the first and only drug approved for the treatment of Rett syndrome, an orphan disease in children.

“They’re got their drug at US$175,000 per patient, so that a very, very attractive opportunity,” she said.

“Then you look in the space that we’re in, there’s nothing approved for FSGS but there’s another rare kidney disease called IGA Neuropathy (IgAN) and there’s been two drugs approved for that quite recently. 

“The first one, Calliditas’ Tarpeyo drug is retailing at US$14,000 per patient per month, and the other one, Travere’s Sparsentan treatment, is retailing for US$9900 per patient per month. 

“That is obviously higher than average, but again, it puts it into perspective that it’s a really attractive opportunity.”


Exclusivity period guarantees monopoly

The exclusivity is another element of ODD that makes developing an orphan drug commercially worthwhile, with most jurisdictions offering extra time for paediatric diseases. 

“It’s a period of time that your patents cannot be challenged and a generic cannot enter the market, so it’s a really great opportunity to get a monopoly on the market and get your money back on all of those expenses of developing the drug as well as profit or return for shareholders,” Dr Webster said.

“And if you get a label that includes children, you get an extra two years in Europe and extra six months in the US. 

“Now, that might not sound much, but actually, when you think about that pricing of US$9900 per patient per month, that’s a lot – so those exclusivity periods are invaluable.”

Neuren CEO Jon Pilcher agrees that exclusivity is an attractive incentive, as the drug is commercially protected because the regulator won’t approve a generic for that timeframe.

“They are quite lengthy periods and the importance of that is generic companies go and challenge patents and try to knock them out but that doesn’t matter, because if that was to happen, you would still have this protection for that period.”

Neuren’s North American partner Acadia has already made the first commercial sale of the drug in the US, with the company expecting a tidy US$40m payment any day now. 

The company is also eligible to receive ongoing royalties on net sales in North America, plus milestone payments of up to US$350 million if a series of four annual sales thresholds are achieved – a nice feather in their financial cap.


Potentially a faster path to market too

Another bonus is these incentives offer a faster approval time, which means a potentially quicker path to market.

“The advantage of having orphan drug designation means that we only have to do one single Phase 3 study, and we have built in two interim end points – so we don’t have to wait for the full study to know how it is progressing,” Dr Webster said.

“You can also get a review period that’s a lot shorter than the standard review periods for drug applications, so it all adds up.” 

The first end point for DXB’s Phase 3 trial will be towards the first quarter of 2024, and after the second interim end point, or accelerated approval endpoint, it could mean the company can take the drug to market earlier.

“If successful, the second interim end point means we could go to market halfway through the study in some territories, with the study continuing to the end point in the background,” Dr Webster said.


DXB and NEU share prices today:


Who else has orphan drug designation?

Race Oncology (ASX:RAC) has FDA orphan drug designation for its Phase 2/3 cancer drug Zantrene for Acute Myeloid Leukaemia (AML) and recently received human ethics approval from the Hunter New England Human Research Ethics Committee for the observational stage of a planned Phase 1/2b cardioprotection trial.

The company is also exploring the drug as a new therapy for melanoma and clear cell renal cell carcinoma, and a recent report from Triangle Insights Group flagged that Zantrene is well-positioned for use as a cardio-protective and anti-cancer agent.

Antisense Therapeutics (ASX:ANP) also has ODD and Rare Pediatric Disease Designation  in the US for its drug ATL1102 for the treatment of Duchenne muscular dystrophy (DMD).

In the March quarter, the company nabbed approval from the Turkish Medicines and Medical Device Agency (TMMDA) to conduct a Phase IIb trial of ATL1102 in non-ambulant boys with DMD, they also received trial approval in Bulgaria in April – with results from the blinded phase of the trial expected in 1H 2024.

Prescient Therapeutics (ASX:PTX) was granted Orphan Drug Designation from the FDA for its PTX-100 drug for the treatment of all T cell lymphomas in March and is now working to schedule a Phase 2 trial.

Oncology company Kazia Therapeutics’ (ASX:KZA) paxalisib drug has ODD status for glioblastoma (the most common and most aggressive form of primary brain cancer in adults) and for Diffuse Intrinsic Pontine Glioma (DIPG), a rare, fast growing brain cancer in children, and for atypical teratoid/rhabdoid tumours (AT/RT).

Final data from the company’s Phase 3 trial for glioblastoma is expected in H2 CY23, with data from the Phase 2 international trial of paxalisib for DIPG expected in in H1 FY23.

Alterity Therapeutics (ASX:ATH) has Orphan Drug Designation in Europe and the US for ATH434 for the treatment of Multiple System Atrophy (MSA), a neurodegenerative disorder.

The Phase 2 clinical trial for the drug now has sites open for recruitment in five countries with participants in the US and Europe receiving their first dose in the March quarter.

Radiopharm Theranostics (ASX:RAD) has US ODD for its DUNP19 technology for the treatment of osteosarcoma, a type of bone cancer that primarily affects children, adolescents and young adults, along with ODD for its Ga68-Trivehexin technology for imaging of patients with pancreatic ductal adenocarcinoma (PDAC). 

And AdAlta (ASX:1AD) has the status in the US for its AD-214 treatment of idiopathic pulmonary fibrosis, a condition where the lung tissue becomes scarred, with Phase 2 studies planned.


RAC, ANP, PTX, KZA, ATH, RAD and 1AD share prices today:


At Stockhead we tell it like it is. While Dimerix and Prescient Therapeutics are Stockhead advertisers, they did not sponsor this article