Drug repositioning to bring forgotten assets from shelves to patients

A problem very rarely spoken about is the treatments that are promising, but are not developed further. Ben Hargreaves finds that these drug candidates are often left in limbo and never see the light of day, except now certain organisations are looking to rectify this.

The success rate for pharmaceutical R&D is remarkably low. The expense of running clinical trials means that the industry has to be selective when deciding which assets to develop. Inevitably, this means that once-promising treatments can be lost from the pipeline, with companies forced to select the candidates that are considered to have the highest chance of success or potential financial return.

For patients, this can represent a missed opportunity, as possible treatments for their condition are left languishing undeveloped. For the wider industry, it means an asset that could be moving towards commercialisation and revenue generation is instead remaining untapped within a company’s IP portfolio.

This has led to some companies being formed to develop potential drug candidates that would otherwise not see the light of day. A recent example and success story of such a model was the $7.1 billion deal between Roche and Telavant for a drug candidate developed through a joint venture between the latter company and Pfizer.

However, this business model is not widespread and there are still many more assets that are partially developed, only to be abandoned. This leaves many drug prospects needing a champion to return to the clinic. One potential source of backers to get assets back into development are non-profit organisations. pharmaphorum spoke to Annette Bakker, CEO of the Children’s Tumor Foundation, a foundation that works to improve the health and well-being of individuals affected by neurofibromatosis (NF), about the organisation’s work on drug repositioning to bring more treatments to those living with NF.

Shelved assets

Bakker noted that the need to successfully reposition drugs will only grow in the future because of one major trend that has developed across the industry: the way large pharma conducts R&D. As can be seen across many M&A deals, bigger companies are snapping up biotechs in greater numbers. This is one effective way companies can bolster their pipelines, whilst reducing some of the risk of the assets failing. However, one of the side-effects of this approach, Bakker stated, is that the biotechs’ lead asset is often the focus of development, while some of the drug candidates further away from commercialisation are left undeveloped.

This is where Bakker sees an opportunity: “They have this one drug that they will buy for billions, and the other assets that are from the biotech, they're just shelved – even if they have potential medical value and if they already have a data package that could bring them very quickly into development. With all these biotechs being bought by major pharma, we're getting a lot of fridges filled with what I call ‘shelved assets’ that I think have a huge value for rare disease.”

Time, talent, and treasure

The undeveloped assets are effectively left in limbo. They are not of sufficient commercial value to warrant a major investment by the buying company: the team that developed them may have already been disassembled and any data generated is unorganised for any potential future development. Despite this, Bakker stated that there is still potential for these assets. The commercial value could still be there, if not for a large-scale company, then potentially for a smaller one, and the patent protection is still present. The question is how to bridge this gap between the forgotten assets and their potential use in treatments.

Bakker believes that this is where non-profits can step in to provide the “time, talent, and treasure” to make sure the assets do not stay on the shelf. She referred to CTF as ‘filling the gaps’ that exist in the current pharma model: by being able to provide the money to start clinical trials, by having the right individuals with disease and drug development expertise, and the necessary focus to be able to work on getting a single asset back into the clinic.

“I see a huge shift in non-profits being populated with pharma veterans that really know how to do drug discovery and drug development and can play a unique role in the R&D ecosystem because we are not conflicted. We can talk to academics today, to pharma tomorrow, to regulators the day after, and then we talk to the patients as well. So, we can move quickly if you get the right people around the table,” Bakker said, on the evolving role of non-profit organisations.

Bearing fruit

The fruits of CTF’s efforts were born out through the work the non-profit has carried out with Pfizer and SpringWorks on mirdametinib. Bakker explained that the development into the asset had stalled, as it appeared AstraZeneca’s Koselugo (selumetinib), which was moving through trials at the same time, held a competitive advantage by being set for an earlier approval. AZ’s treatment was later approved for NF1, but CTF believed that Pfizer’s asset was equally important for patients due to its differentiated action. The foundation worked with Pfizer to understand the potential of the asset, with SpringWorks being spun-out to develop mirdametinib and three other assets. At the end of 2023, SpringWorks was able to post positive topline results from a phase 2b trial, and submit a data package to the FDA.

A spokesperson for SpringWorks told pharmaphorum that the rolling submission of its NDA would set the company up for potential approval in 2025 in the US. A further marketing authorisation application will be submitted in Europe during the second half of 2024. Regarding the potential drug’s position on the market, the spokesperson said: “We were very pleased to see that mirdametinib treatment demonstrated deep and sustained tumour volume reductions, improvement in pain and health-related quality of life across both the adult and paediatric cohorts, and a manageable and tolerable safety profile, which we believe will continue to be a key distinction from other MEK inhibitors.”

For CTF, this marks a success for its approach, but there is still more work to be done to ensure that further potential treatments are not left on the shelf.

“We need more and more companies that are spun out of big pharma companies to show the world that this is the right way to go. I want to get drug ‘recycling’ to be the philosophical and ethical thing to do for the patients because that's our fiduciary responsibility as a society to our patients. We cannot let them down. If there are good drugs in the fridges, they have to come out,” Bakker concluded.