May 15, 2015 (Vol. 35, No. 10)
Radiopharmaceutical Company’s Compounds Combine Therapeutic and Diagnostic Capabilities
Advanced Accelerator Applications (AAA) is pioneering work in theragnostics—the blending of therapeutics and diagnostics capabilities into one drug for nuclear medicine applications.
“Theragnostics is a very straightforward proposition for physicians dealing with nuclear medicine,” says Stefano Buono, AAA’s CEO and founder. This approach attaches radioisotopes to therapeutic molecules to deliver therapeutics and imaging in one injection. “The isotopes don’t change the nature of the chemical entity, and they don’t change the ability for targeting,” he explains.
Traditionally, most radioactive compounds used in healthcare are active about 10 hours. AAA has produced more than 30,000 batches of such compounds for medical centers since spinning out of CERN in 2002. The company has expanded its work to include therapeutic compounds. “We can make therapeutic, radioactive compounds that have a three-day window,” Buono asserts.
Unlike traditional nuclear medicine approaches, which can’t treat metastatic disease, theragnostics is effective for tumors that are so widespread they can’t be treated with radiotherapy or surgery.
These new capabilities, Buono insists, have the potential to transform nuclear medicine from a niche therapy to “a pillar of medicine.”
AAA has several compounds in development. Lutathera®, in Phase III development for the treatment of neuroendocrine tumors (NETs), is the most advanced. This lutetium-177-labeled somatostatin analogue peptide was granted orphan drug status from the EMA and the FDA. It is approved to treat NETS on a compassionate-use/named-patient basis in nine European nations.
A companion diagnostic, Somakit®, is in preclinical development for positron emission tomography (PET) imaging of NETs. “Somakit and Lutathera are the same drug,” Buono notes.
In practice, a physician would administer Somakit to diagnose and understand the extent of the disease. “If metabolic therapy is chosen, the patient would be injected with Lutathera. Then, the morning after, the patient would undergo full-body scanning to pinpoint the locations of the disease,” Buono explains. “After a few weeks, the patient would return for the second of four treatments.”
From the patient’s perspective, there should be no side-effects. Medically, there is transient hematologic toxicity, but according to Buono, it is unnoticeable by patients. The nausea, fatigue, and hair loss associated with chemotherapy, he says, are nonexistent with Lutathera.
Another diagnostic, Annexin-V128, is in Phase II development to detect apoptosis and necrosis using single-photon emission computed tomography (SPECT) imaging. Apoptosis, which signals cell death, is associated with many diseases. It is useful in oncology, cardiology, and autoimmune disorders.
AAA’s approach to SPECT allows researchers to see the behavior of Annexin-V128 in the body, making the drug a potentially valuable companion diagnostic to monitor therapeutic effectiveness by determining whether a medication creates apoptosis.
Annexin has a long history of diagnostic use, but only recently has it become possible to develop a good Annexin drug. “Some chemical aspects of formulation made it less selective,” Buono points out, “and the manufacturing quality wasn’t up to pharmaceutical standards.” As those hurdles have been overcome, AAA is identifying the most urgent clinical priorities and planning clinical trials.
“Theragnostics can be applied as a diagnostic and therapeutic for any cancer,” Buono says. AAA plans to move other drugs into the clinic this year, and the industry also has several in early phases of development. But, like other therapeutic molecules, the molecules used for theragnostics are effective only if the tumor has the appropriate drug receptor. SPECT or PET imaging can determine that.
“Radionuclear medicine,” he emphasizes, “is more targeted and better for patients.”
Nuclear Medicine’s Moment
This is a pivotal point for nuclear medicine. “In therapeutics, using electrons to treat metastatic disease is at its beginnings,” Buono advises. “It’s a novel idea with infinite possibilities.
Theragnostics’ other aspect, nuclear diagnostics, “will evolve into a driving force for cost-effective, personalized medicine,” he predicts. “The development of companion diagnostics speeds treatments and better ways to monitor their progress.”
“AAA has experienced continuous growth and is very strong in Europe,” Buono says. With the longer activation life of AAA’s theragnostics compounds, they are likely to be introduced into the United States and Canada.
The January 2015 acquisition of Atreus Pharmaceuticals (now AAA Canada) was an important step in the company’s growth. Atreus was developing its Annexin drug, Buono recalls. “We had acquired more than 50% of Atreus to move from the academic to pharmaceutical environment.” After clinically evaluating Atreus’ Annexin drug, AAA gained full control of it by completing the Atreus acquisition.
“We want to continue to expand and be a partner for nuclear medicine products. We hold or exclusively license 55 issued patents, and have a full pipeline in the preclinical stage,” Buono declares. “We want to be a pharmaceutical company that delivers the full potential of nuclear medicine.”
Advanced Accelerator Applications
Location: 20 Rue Diesel, 01630 Saint-Genis-Pouilly, France
Phone: 33 (0)4 50 99 30 70
Principal: Stefano Buono, CEO and Founder
Number of Employees: 340
Focus: Advanced Accelerator Applications is pioneering theragnostics, a means of combining imaging and therapeutics into one compound. It also manufacturers diagnostic PET and SPECT molecular nuclear medicine products in Europe.