The first big win for radiopharma?

Today might be the first big win for radiopharmaceuticals. Indeed, ITM, a German radiopharma company has announced positive topline results from its phase 3 COMPETE trial, evaluating ITM-11 in patients with inoperable, progressive grade 1 or grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). 

“Despite advances in cancer treatment, significant unmet needs remain, particularly in balancing efficacy and safety. Radiopharmaceuticals like ITM-11 are novel cancer treatments that combine two critical components: a targeting molecule and a therapeutic radioactive isotope,” said Andrew Cavey, chief executive officer (CEO) of ITM.

While radiopharmaceuticals are attracting more and more investment and candidates are showing great promise, the field still awaits its first big win. The COMPETE trial is the first to show that a targeted radiopharmaceutical therapy can outperform a molecular targeted therapy in a head-to-head phase 3 study for GEP-NETs. This success underscores the growing potential of targeted radiotherapies to complement and, in some cases, surpass conventional cancer treatments.

So, how does ITM-11 work and what could it mean for the industry? Let’s find out.

What does the radiopharma industry look like?

The concept of radiopharmaceuticals dates back several decades, primarily used in diagnostic imaging. However, the field has recently experienced rapid development due to advances in radioisotope-based therapies, multimodality bioimaging technology, nanotherapeutics, and interventional oncology.

The radiopharmaceutical market is experiencing significant growth. A report by The Insight Partners projects that by 2031, the market is expected to reach $26.51 billion, increasing from $9.07 billion in 2023.

This growth is driven by the success of therapies like Novartis’ Pluvicto and Lutathera, which have demonstrated the efficacy of targeted radioligand therapies in treating specific cancers.

This success has spurred substantial investments and acquisitions in the sector. For instance, Novartis’ $1 billion acquisition of Massachusetts-based Mariana Oncology underscores the growing interest in radiopharmaceuticals for cancer treatment. Similarly, Eli Lilly’s $1.4 billion acquisition of Point Biopharma highlights the pharmaceutical industry’s commitment to expanding its radiopharmaceutical portfolios.

Technology-wise, innovations in targeted radiopharmaceuticals (TRPs) are transforming oncology. TRPs, composed of a targeting molecule, linker, chelating agent, and radionuclide, aim to replace non-targeted radiotherapies by delivering radiation directly to cancer cells, minimizing damage to healthy tissue. The development of TRP diagnostics as companion tools for these therapies further enhances their precision and effectiveness.

Additionally, companies are exploring new radioisotopes, such as actinium-225, which emits potent alpha radiation capable of effectively killing cancer cells. However, the limited supply of such isotopes presents challenges, prompting investments in production capabilities to meet growing demand.

Beyond challenges in future commercialization and production of radiopharmaceuticals, the field still needs some big wins to capitalize further on its promise and step away from its status of niche within oncology. Are IMT-11’s results in phase 3 the first win that radiopharma needs? 

IMT-11, how does it work?

ITM is at the forefront of radiopharmaceutical innovation, with its lead candidate, ITM-11, showing promise in treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

GEP-NETs are a rare type of cancer that arises from the neuroendocrine cells found throughout the gastrointestinal tract and pancreas. These cells produce hormones and neurotransmitters that help regulate various bodily functions, such as digestion.

ITM-11 is a targeted radionuclide therapeutic composed of two key components. On the one hand, edotreotide is a somatostatin receptor (SSTR) analog peptide derived from octreotide, designed to bind with high affinity to somatostatin receptors that are overexpressed on neuroendocrine tumor cells. On the other hand, no-carrier-added (n.c.a.) Lutetium-177, is a synthetic, low-energy beta-emitting therapeutic radioisotope.

Upon administration, edotreotide targets and binds to somatostatin receptors on tumor cells. This binding facilitates the internalization of ITM-11 into the tumor cells. Once inside, the n.c.a. Lutetium-177 decays, emitting cytotoxic medium-energy beta particles with a path length of up to 1.7 mm in soft tissue. This localized radiation effectively destroys tumor cells while minimizing damage to surrounding healthy tissues.

“ITM-11 is unlike other radiopharmaceuticals that target SSTR for two reasons. First, because it uses n.c.a. lutetium which is more user-friendly for healthcare providers than other forms of Lu-177. Second, because of the design of the clinical trials exploring its use,” said Cavey.

Why is the phase 3 COMPETE trial important in the field?

The phase 3 COMPETE trial has positioned ITM-11 as a frontrunner in the radiopharmaceutical field by demonstrating superior clinical outcomes. Indeed, the results mark the first time a radiopharmaceutical therapy has outperformed a molecular targeted therapy in a head-to-head phase 3 study. ITM-11 achieved a clinically significant and statistically robust improvement in progression-free survival (PFS) compared to everolimus, a targeted molecular therapy. 

ITM-11 was well-tolerated, with a favorable safety profile observed. This is critical for GEP-NET patients, many of whom require long-term treatment. Dosimetry assessments highlighted ITM-11’s ability to deliver targeted radiation to tumor cells while sparing healthy tissues, reinforcing its precision and safety. It is safe to say safety has been a concern about radiopharmaceuticals so these results ought to strengthen stakeholders’ confidence

Additional outcomes, such as overall survival, objective response rate, and quality of life metrics, are still being evaluated.

“Radiopharmaceuticals are setting new standards of care in oncology treatment.  The uptake of some already approved medicines, coupled with a robust set of phase 1, 2 and 3 trials currently in progress, including our own, is a testament to the progress and pace of radiopharmaceutical development. I believe that robust clinical trials like COMPETE, and our ongoing phase 3 COMPOSE trial, will help contribute to changes in the overall oncology treatment landscape,” explained Cavey.

Indeed, the COMPETE trial results could represent a historical moment for radiopharmaceuticals, a field still perceived as a niche within oncology. By outperforming everolimus, a well-established targeted therapy, ITM-11 has proven that radiopharmaceuticals can be a first-line treatment option for certain cancers. This could lead to a more widespread acceptance of radiopharmaceutical therapies.

Indeed, these late-stage positive results give credibility to ITM-11 and the entire sector, potentially giving an investment boost to radiopharma in 2025, which has already been going strong in 2024.

ITM’s pipeline includes trials for other indications, such as glioblastoma and clear cell renal cell carcinoma. The success of COMPETE signals that radiopharmaceuticals have the potential to address a wider range of cancers.

With a potential U.S. Food and Drug Administration (FDA) submission in 2025, ITM-11 may become one of the first radiopharmaceuticals to achieve regulatory approval based on head-to-head superiority against a molecular therapy. This would set a precedent for other radiopharma regulatory approvals.

For patients, many cancers, including GEP-NETs, lack effective, targeted treatment options. Radiopharmaceuticals like ITM-11 can fill this void by offering precise, minimally invasive, and effective therapies.

Radiopharma 2.0 what’s next?

Cavey noted that, although radiopharmaceuticals are already mainstream treatment options for certain tumor types, such as neuroendocrine tumors and prostate cancer, the field still faces challenges.

“For their use to become more widespread, several challenges need to be overcome: More clinical data is needed, across tumor types, across indications, and across molecular targets; improved radioisotope availability and supply; investments in capacity need to follow in many countries; improved coordination across the multidisciplinary teams; more harmonized policies”

One of the primary obstacles facing the industry is the limited availability of critical isotopes, such as actinium-225. 

This isotope is essential for certain radiopharmaceutical therapies, but its scarcity has hindered the progression of clinical trials and the broader application of these treatments. Historically, supply is predominantly sourced from decaying Cold War-era stockpiles, making it difficult for pharmaceutical companies to meet the growing demand. Efforts are underway to scale up production, but the processes remain complex and costly.

Additionally, manufacturing and logistical complexities present significant hurdles. The production of radiopharmaceuticals requires specialized facilities and strict safety protocols to handle radioactive materials. Ensuring a seamless supply chain, from manufacturing to delivery, is crucial to maintaining the efficacy and safety of these therapies. Educating logistics teams about the safe handling of radioisotopes and organizing specialized transport are essential steps in this process.

It’s going to be interesting to see how ITM handles the next steps in this challenging landscape. As potentially the first TRP to reach the market based on head-to-head superiority against a molecular targeted therapy, ITM-11 is an important case for the field.

In terms of supply and manufacturing, Cavey is confident. “Manufacturing and logistics are cited as barriers because radioisotopes have limited half-lives, meaning stockpiling is not possible, and logistics need to be managed carefully. These are areas in which ITM has been leading for 20 years:  we have two manufacturing sites in the Munich area and are the leading supplier of n.c.a. Lu-177.”

Cavey also observed that regulations are starting to adapt to this rapidly evolving field. “We are seeing very active engagement by medicines regulators and radioprotection agencies across the world, who are trying to adapt to the new technologies and promise offered by radiopharmaceuticals.”

In this area full of opportunities, ITM and its candidate aren’t the only ones to follow of course:

• Lutetium (^177Lu) vipivotide tetraxetan: Developed by Novartis, this therapy targets prostate-specific membrane antigen (PSMA) in metastatic castration-resistant prostate cancer. It has shown promising results in clinical trials and is anticipated to gain further traction in 2025.
• Actinium-225-based therapies: Companies like Eli Lilly are investing in the production of actinium-225 to develop targeted cancer treatments. Their recent acquisition of Point Biopharma and investment in isotope supplier Ionetix indicate their belief in radiotherapeutics.
• Lead-212-based therapies: Sanofi’s partnership with OranoMed focuses on developing treatments using lead-212 isotopes, which emit potent alpha radiation. Their lead candidate targets neuroendocrine tumors and could launch in 2026 following successful clinical trials.

As the industry advances, addressing the challenges of isotope supply, manufacturing, and logistics will be crucial. Continued investment in research and infrastructure, along with strategic partnerships, will play a vital role in overcoming these hurdles. This is the reason why results such as the ITM-11’s are essential – there is still a long road ahead, and it’s important to record wins along the way to sustain or boost stakeholder confidence and attract new investors.

“The field is really at a pivotal moment. In the coming years, we’ll likely see advances across every component of radiopharmaceuticals: innovations in isotope use, such as with Terbium-161, the development of new peptides, and the identification of novel cancer targets.  We also see a surge in clinical data as critical to informing regulatory pathways and expanding patient access,” said Cavey. There is a lot to look forward to in the radiopharma sector.