After decades of neglect from big pharma, radiopharmaceuticals are generating major oncology deals globally. This could lead to a boom in cancer drugs that can serve as both treatments and diagnostics, or “theranostics.”
Over the last few years, there has been big activity from companies developing drugs that use radioactivity to destroy tumors. Just this year, for example, large venture rounds have gone to the radiopharmaceuticals startups Precirix, Ariceum Therapeutics and Ratio Therapeutics. Additionally, many collaboration and licensing deals have coalesced around the sector, including between Actinium Pharmaceuticals and Immedica Pharma, and between Telix Pharmaceuticals and China Grand Pharma.
“The market is clearly hot at the moment and, whilst the majority of the investment has been in the U.S., we are also seeing a high level of interest and activity in Europe and the Far East,” said Paul Edwards, former CEO of the U.K. radiopharmaceuticals developer NanoMab.
Nuclear medicine involves using radioactivity for the diagnosis or treatment of a range of diseases. In cancer, for instance, a radioactive atom called a radionuclide can be attached to a drug that can hunt down tumors in the body. This opens up avenues for theranostics, where you can image tumors and destroy them more easily than with conventional therapies such as chemotherapy.
“Unlike chemotherapy or immunotherapy, responses with radiopharmaceuticals agents typically do not require many months of therapy and are often observed after only a few injections,” said Jamal Temsamani, Drug Development Director at Vect-Horus.
A classic theranostic method that has been used since the 1950s is radioactive iodine; one isotope of iodine can be used to image the spread of thyroid tumors, and another can be used to destroy them.
A newer approach, developed by the French company Advanced Accelerator Applications (AAA), tackles neuroendocrine tumors using a molecule called dotatate. This drug seeks out proteins on the surface of some tumors. One type of radionuclide can be attached to dotatate to image the tumors and another can be attached to eliminate them.
For decades, the clinical development of radiopharmaceuticals was mainly restricted to academic efforts. However, apart from some early radiopharmaceutical approvals such as of Zevalin and Xofigo, big pharma only began to take the field seriously after AAA forged the path with dotatate.
AAA’s lead candidate was approved in the EU with the brand name Lutathera in September 2017. Just a month after, Novartis purchased AAA for a hefty $3.9 billion, and in 2018, the U.S. followed Europe by approving Lutathera. Novartis would go on to acquire another radiopharmaceutical developer, Endocyte, for $2.1 billion in 2018. In late 2019, meanwhile, the biotech Progenics — with several radiopharmaceutical products approved by the U.S. Food and Drug Administration — was snapped up by Lantheus Holdings.
“It was really AAA coming along and doing a formal prospective, randomized controlled study that has been a game-changer,” noted Greg Mullen, CEO of the U.K. company Theragnostics. “If you look at how Novartis sees radionuclide therapy, it sees it as one of the pillars that it wants to develop as a cancer therapy.”
There are a number of nuclear medicine options available for patients with cancer, particularly in diagnostics. However, to really fulfil the potential of theranostics in precision medicine, the range of technology available needs to be expanded.
“The current theranostics field is still tending to focus on just a few small molecules and specific radioisotopes,” said Edwards. He added that the drugs need to be able to target many more biomarkers and carry more types of radionuclides.
The firm Theragnostics aims to expand the range of theranostics by harnessing a class of drugs called PARP inhibitors. These drugs, which include AstraZeneca’s Lynparza, prevent cancer cells from repairing damaged DNA, and can work in a wide range of tumor types. Theragnostics licensed AstraZeneca’s PARP inhibitor intellectual property in 2019 with the plan to radiolabel some of these drugs. The firm is developing diagnostic and therapeutic versions of the compounds in phase 1 testing.
“That’s what’s different from all of the other cancers where you have a specific marker for a specific cancer and even an indication,” said Mullen. “Here, you have what I call a potential pan-cancer market.”
Meanwhile, NanoMab and Precirix are developing radiolabeled drugs based on antibodies from the camelid family, which include camels, llamas and alpacas. These antibodies are smaller and more stable than human antibodies, allowing them to penetrate tumors more easily. Precirix’s phase 2-stage lead candidate is designed to treat breast cancer that has spread to the brain, while NanoMab is developing a diagnostic that could let clinicians noninvasively check whether checkpoint inhibitor drugs are working.
The European life sciences scene has been one of the main driving forces in kickstarting theranostics, with companies such as AAA, Novartis and AstraZeneca leading the way. However, the same might not be true for the future of the field. The U.S., for example, is producing some rising stars including Rayze Bio, Y-mAbs Therapeutics and Aktis Oncology.
Additionally, as with many other therapies, the clinical development of theranostics has been negatively affected by the COVID-19 pandemic. This is partly because radiotherapy requires patients to travel to hospitals, which have struggled with COVID-19 outbreaks for the last couple of years. Nevertheless, theranostics continues to gain momentum, and will likely be able to expand its range to new cancer biomarkers and indications going forward.
“Immunotherapy took the best part of 15 to 20 years to get going,” reflected Mullen. “Now nuclear medicine is the next immunotherapy.”
This article was originally published in November 2020 and has since been updated with the latest in radiopharmaceuticals.