• Even after showing effectiveness in late-stage trials, as many potential treatments fail to reach the market
  • There are several reasons for drugs not making it to market including commercial decisions by a company 
  • Several ASX-listed pharmaceutical companies are repurposing or resurrecting abandoned drugs

Despite showing effectiveness in late-stage trials, up to 25% of all potential treatments never make it to market, according to Race Oncology CEO Dr Daniel Tillett.

While some blame lies with trial design or manufacturing challenges, a surprising culprit is commercial decisions, said Tillett who has has more than 25 years’ experience in the biotech industry.

He is also the founder and CEO of Nucleics, an Australian biotechnology company focused on DNA sequencing and genomics,  and has been a senior lecturer within the School of Pharmacy and Applied Science at La Trobe University.

“During the long process of developing a new drug (a decade or more), companies sometimes change their commercial focus,” he said.

“As a result, the new drug may no longer fit the commercial aims of the company, or the patent life on the drug may be too short to recoup the launch and marketing costs.”

Tillett said M&A within the pharmaceutical industry can often spell doom for promising drugs.

“If a company developing an effective treatment is acquired by another with no interest in the drug, it often gets abandoned even at a very late stage in development,” he said.

Tillett says another common reason for an effective drug being dropped is that it may be difficult and complex to administer.

“For example, the drug may require complex equipment or can only be performed in a hospital by trained personnel,” he said.

“This can make the drug uncompetitive commercially against other treatments on the market, even when those treatments are inferior.”


Resurrecting potentially effective drugs

Tillett said there were several different ways that abandoned drugs could be resurrected with one of the most common being out-licensing, where the original developer of the drug sells the IP and the associated drug data package to a new company (in-licensing) who then re-start clinical development of the drug.

“Many small biotechs and pharma companies fast-track their clinical development program by picking up drug assets abandoned by large pharmaceutical companies,” he said.

Tillett said an alternative approach to resurrect an abandoned or underutilised drug was to reformulate the drug to make it more useful, allowing different means of delivery to a patient such as making an oral drug into a drug delivered by injection.

“This approach generates new IP and patents, allowing the successful marketing of a drug where the original patent on the drug had expired,” he said.

He said a similar approach has been used where drug combinations can be developed as an aid to patient convenience, such as one tablet instead of many, and to ensure the best balance of drugs is maintained in the patient.

Tillett said abandoned drugs could also be resurrected by repurposing to treat a very rare disease. Orphan Drug Designation (ODD) in the US and EU provides 7- and 10-year market exclusivity, irrespective of patent protection, for drugs that effectively treat rare diseases.

“This can enable a pharmaceutical company the means to recoup the costs of bringing a drug to market for a rare disease when it would otherwise face immediate generic competition,” he said.


Drugs successfully resurrected or repurposed

Tillett says two famous examples of effective drugs being resurrected or repurposed are Abraxane and Cubicin.

Abraxane (nab-paclitaxel) is a reformulation of Taxol (paclitaxel) developed by Bristol Myer Squibb to overcome solubility and toxicity issues with the original formulation, caused by the insolubility of paclitaxel.

“While an effective anticancer agent in breast, lung and ovarian cancers, the original Taxol formulation required the use of the very toxic Cremophor EL formulation, leading to long infusion times and steroid pre-treatment to reduce hypersensitivity reactions,” he said.

“Despite these limitations, by 2000, sales of Taxol exceeded US$1.5 billion before becoming a generic drug.

“American Biosciences recognised these issues and developed a nanoparticle formulation of the by-now generic paclitaxel to overcome the solubility and toxicity issues.”

Tillett said the formulation ultimately marketed by Abraxis Oncology using the brand name Abraxane established itself as the preferred taxane at a branded drug price because it offered:

  • Shorter infusion time (30mins vs 3hrs)
  • No hypersensitivity/infusion reactions or no need for steroid pre-treatment
  • In some trials, clinical superiority over Taxol.

Abraxis was acquired by Celgene in 2010 for US$2.9 billion with annual sales of Abraxane peaking at US$1.25 billion in 2020.

Tillett said an antibiotic Cubicin (daptomycin) was successfully repurposed by Cubist Pharmaceuticals after pharmaceutical giant Eli Lilly abandoned the drug due to serious toxicity issues.

“Eli Lilly out-licensed the rights to daptomycin, along with a licence to the underlying IP related to the compound, to Cubist four years after shelving clinical development.

“Cubist scientists identified the cause of human toxicity and filed a patent for a once-daily dosing to minimise the adverse effects of the drug.

“Annual sales of Cubicin reached US$1 billion before Cubist was acquired by Merck & Co for US$8.4 billion in 2014.

There are several ASX-listed biotech companies resurrecting or repurposing abandoned or under utilised drugs. Here are some we’ve noticed.


Race Oncology (ASX:RAC)

Race Oncology is itself resurrecting the anticancer drug bisantrene via reformulation and repurposing.  Tillett said bisantrene was originally developed in the 1970s and ’80s by a small French pharmaceutical company called Lederle Laboratories as a lower cardiotoxic alternative to the anthracycline class of chemotherapeutics.

“Unfortunately, the original Lederle formulation of bisantrene is highly insoluble in blood, making the use of bisantrene complex and difficult,” Tillett says.

“After being unable to overcome the solubility issue, Lederle abandoned the commercial development of bisantrene despite it showing significant efficacy in several cancers including breast, ovarian and leukaemia.”

The drug was even approved for the treatment of Acute Myeloid Leukaemia (AML) in France.

“After identifying the potential of bisantrene, Race Oncology scientists were able to solve the solubility issue through reformulation and identify that when used in combination with the anthracyclines, it can prevent the serious cardiotoxicity caused by these anthracyclines while also improving their anticancer activity,” he says.

“Race is about to begin clinical trials of this new formulation in a range of cancer types.”

The company recently announced it had been issued a Certificate of Analysis (CoA) for its first current Good Manufacturing Practice (cGMP) batch of proprietary bisantrene formulation RC220.


PharmAust (ASX:PAA)

Normally it’s an approved human drug being repurposed for another indication in human health, but PAA is repurposing an approved veterinary drug for a different application or indication in human health.

“As such you can not use the same abbreviated regulatory pathway like the 505 (b) (2) for a repurposed human drug for another human indication, you still need to use the traditional 505 (b) (1) as you would for any new drug seeking approval under an NDA,” CEO Dr Michael Thurn told Stockhead.

“Depending on the scope and breadth of the toxicity studies carried out to support veterinary approval you may be able to obtain waivers or truncate the nonclinical toxicity package required to obtain FDA approval.”

Thurn says there are not many examples of a veterinary drug receiving FDA approval for a human indication.

“NASDAQ-listed Tarsus Pharmaceuticals has managed to do this though recently,” he says.

“XDEMVY (lotilaner ophthalmic solution) 0.25% was approved by the FDA in July of 2023 for the treatment of Demodex blepharitis, a prevalent eyelid disease.

“Lotilaner is a potent and selective anti-parasitic that was being utilised in veterinary medicine by Veterinary giant Elanco.”

PAA is repurposing the antihelminth, monepantel, used to treat nematodes infestation in sheep as a potential treatment for Motor Neurone Disease.

“Tarsus is a great case study for PharmAust showing that it is possible to repurpose a veterinary drug for human use and doing so create a US$1.36 billion market cap company and a fantastic return on investment for its shareholders,” Thurn said.

PAA recently announced Macquarie University has given the company approval to conduct an open-label extension study of monepantel in patients with Motor Neurone Disease.


The RAC and PAA share price today:


At Stockhead, we tell it like it is. While Race Oncology and PharmAust are Stockhead advertisers, they did not sponsor this article.