Radiopharmaceuticals are a promising new class of drugs generating lots of excitement for pharmaceutical companies. However, their shorter shelf life means they have differences in manufacturing to antibody-drug conjugates (ADCs) and other emerging drug classes.
That’s the view of Kenneth Baker, PhD, senior director of external manufacturing at Fusion Pharma, who will be speaking about radiopharmaceutical manufacturing at BioProcess International later this month.
“Radiopharma is a burgeoning industry at the moment with lots of big acquisitions being made,” he says, explaining his own company was acquired by AstraZeneca earlier this year. Other important recent acquisitions include the purchase of POINT Biopharma by Lilly and RayzeBio by Bristol Myers Squibb.
“There’s been an explosion in excitement in the space since prostate cancer drug Pluvicto™ was launched by Novartis,” he continues. “I want to give delegates a feel for what it really takes to make a radiopharmaceutical.”
Approved by the FDA in 2022, Pluvicto was estimated to have a potential revenue of $8 billion by 2024, the point at which the company was projected to reach a 250,000-dose capacity.
According to Baker, radiopharmaceuticals work like radiotherapy, a commonly used cancer treatment, but provide localized—rather than external—delivery of a radioisotope.
“We’re basically taking external beam radiation, one of the standards of care in cancer treatment, and internalizing that,” he explains.
Radiopharmaceutical drug structures are like better-known ADCs, but with a radionuclide, rather than a cytotoxic drug, bonded to the targeting antibody and linker molecule. With Fusion Pharma’s products, the patient is given an antibody or peptide conjugated to an indium radioisotope. This allows clinicians to use a CT to detect if their tumor is taking up the antibody before they’re given the active product.
According to Baker, the active product is a second injection, a week later, of an antibody conjugated to an actinium radioisotope.
Ten-day half life
The short half-life, around 10 days, of the radioisotopes means their manufacturing process must run on a weekly basis, and they need to have complex pre-planned logistics to distribute their product worldwide.
“Part of our strategy is having the internal capacity for manufacturing. We use external partners too, and we reserve capacity to produce on demand,” points out Baker.
The company must deal with the usual challenges of manufacturing antibodies, but—unlike with a monoclonal antibody drug—the bulk antibody must be aliquoted into small vials for later downstream use.
Another challenge specific to radiopharmaceuticals is the limited supply of actinium worldwide, meaning shipments don’t always arrive on schedule.
“We have to organize production around isotope availability,” he says. “We work close with the clinical team to make sure the timeline works for the patient. The worst thing would be for them to come in and a dose not to be available.”
If the patient isn’t responding to the first indium isotope injection, their dose must be allocated to another patient or used for research. The company currently has a radioisotope with a peptide targeting molecule in a Phase II clinical trial, and some ADCs in Phase I.
Other challenges include educating external logistics teams about the safety of radioisotopes and the need to organize courier transport if connecting flights go awry.
