cancer drugs

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Radioactive drugs strike cancer with precision

Pharma interest and investment in radiotherapy drugs is heating up.

Enlarge / Pharma interest and investment in radiotherapy drugs is heating up.

Knowable Magazine

On a Wednesday morning in late January 1896 at a small light bulb factory in Chicago, a middle-aged woman named Rose Lee found herself at the heart of a groundbreaking medical endeavor. With an X-ray tube positioned above the tumor in her left breast, Lee was treated with a torrent of high-energy particles that penetrated into the malignant mass.

“And so,” as her treating clinician later wrote, “without the blaring of trumpets or the beating of drums, X-ray therapy was born.”

Radiation therapy has come a long way since those early beginnings. The discovery of radium and other radioactive metals opened the doors to administering higher doses of radiation to target cancers located deeper within the body. The introduction of proton therapy later made it possible to precisely guide radiation beams to tumors, thus reducing damage to surrounding healthy tissues—a degree of accuracy that was further refined through improvements in medical physics, computer technologies and state-of-the-art imaging techniques.

But it wasn’t until the new millennium, with the arrival of targeted radiopharmaceuticals, that the field achieved a new level of molecular precision. These agents, akin to heat-seeking missiles programmed to hunt down cancer, journey through the bloodstream to deliver their radioactive warheads directly at the tumor site.

Use of radiation to kill cancer cells has a long history. In this 1915 photo, a woman receives “roentgenotherapy”—treatment with X-rays—directed at an epithelial-cell cancer on her face.

Use of radiation to kill cancer cells has a long history. In this 1915 photo, a woman receives “roentgenotherapy”—treatment with X-rays—directed at an epithelial-cell cancer on her face.

Wikimedia Commons

Today, only a handful of these therapies are commercially available for patients—specifically, for forms of prostate cancer and for tumors originating within hormone-producing cells of the pancreas and gastrointestinal tract. But this number is poised to grow as major players in the biopharmaceutical industry begin to invest heavily in the technology.

AstraZeneca became the latest heavyweight to join the field when, on June 4, the company completed its purchase of Fusion Pharmaceuticals, maker of next-generation radiopharmaceuticals, in a deal worth up to $2.4 billion. The move follows similar billion-dollar-plus transactions made in recent months by Bristol Myers Squibb (BMS) and Eli Lilly, along with earlier takeovers of innovative radiopharmaceutical firms by Novartis, which continued its acquisition streak—begun in 2018—with another planned $1 billion upfront payment for a radiopharma startup, as revealed in May.

“It’s incredible how, suddenly, it’s all the rage,” says George Sgouros, a radiological physicist at Johns Hopkins University School of Medicine in Baltimore and the founder of Rapid, a Baltimore-based company that provides software and imaging services to support radiopharmaceutical drug development. This surge in interest, he points out, underscores a wider recognition that radiopharmaceuticals offer “a fundamentally different way of treating cancer.”

Treating cancer differently, however, means navigating a minefield of unique challenges, particularly in the manufacturing and meticulously timed distribution of these new therapies, before the radioactivity decays. Expanding the reach of the therapy to treat a broader array of cancers will also require harnessing new kinds of tumor-killing particles and finding additional suitable targets.

“There’s a lot of potential here,” says David Nierengarten, an analyst who covers the radiopharmaceutical space for Wedbush Securities in San Francisco. But, he adds, “There’s still a lot of room for improvement.”

Atomic advances

For decades, a radioactive form of iodine stood as the sole radiopharmaceutical available on the market. Once ingested, this iodine gets taken up by the thyroid, where it helps to destroy cancerous cells of that butterfly-shaped gland in the neck—a treatment technique established in the 1940s that remains in common use today.

But the targeted nature of this strategy is not widely applicable to other tumor types.

The thyroid is naturally inclined to absorb iodine from the bloodstream since this mineral, which is found in its nonradioactive form in many foods, is required for the synthesis of certain hormones made by the gland.

Other cancers don’t have a comparable affinity for radioactive elements. So instead of hijacking natural physiological pathways, researchers have had to design drugs that are capable of recognizing and latching onto specific proteins made by tumor cells. These drugs are then further engineered to act as targeted carriers, delivering radioactive isotopes—unstable atoms that emit nuclear energy—straight to the malignant site.

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US drug shortages reach record high with 323 meds now in short supply

Terrible —

The shortages affect everything from generic cancer drugs to ADHD medication.

Takeda Pharmaceutical Co. Adderall XR brand medication arranged at a pharmacy in Provo, Utah, in November 2023.

Enlarge / Takeda Pharmaceutical Co. Adderall XR brand medication arranged at a pharmacy in Provo, Utah, in November 2023.

Drug shortages in the US have reached an all-time high, with 323 active and ongoing shortages already tallied this year, according to data collected by the American Society of Health-System Pharmacists (ASHP).

The current drug shortage total surpasses the previous record of 320, set in 2014, and is the highest recorded since ASHP began tracking shortages in 2001.

“All drug classes are vulnerable to shortages,” ASHP CEO Paul Abramowitz said in a statement Thursday. “Some of the most worrying shortages involve generic sterile injectable medications, including cancer chemotherapy drugs and emergency medications stored in hospital crash carts and procedural areas. Ongoing national shortages of therapies for attention-deficit/hyperactivity disorder [ADHD] also remain a serious challenge for clinicians and patients.”

Erin Fox, associate chief pharmacy officer of University of Utah Health, told CBS MoneyWatch, that most of the drugs in short supply are generic, older products, and around half are injectable drugs that require more stringent manufacturing processes.

There are myriad reasons for the hundreds of drug shortages now facing doctors and patients, many of which remain unclear. But, as Ars has reported before, the root cause of shortages of low-cost, off-patent generic drugs is well established. These drugs have razor-thin to non-existent profit margins, driven by middle managers who have, in recent years, pushed down wholesale prices to rock-bottom levels. In some cases, generic manufacturers lose money on the drugs, disincentivizing other players in the pharmaceutical industry from stepping in to bolster fragile supply chains. Several generic manufacturers have filed for bankruptcy recently.

For other drugs, the situation is more complicated. The ADHD drug Adderall, for instance, has been in critical shortage since October 2022, causing millions of patients around the country to struggle to fill their prescriptions. It began when a manufacturing delay for one manufacturer kicked off a shortfall. Although that problem has since been resolved, it came amid a significant increase in Adderall prescriptions, which spiked further during the pandemic when telehealth prescribing became more common. Additionally, because Adderall—made of amphetamine-mixed salts—is a controlled substance, the Drug Enforcement Administration sets limits or “quotas” on how much of it manufacturers can make. Such quotas can exacerbate shortages, ASHP said.

But, in a joint letter with the Food and Drug Administration last August, the DEA said that, by its data, manufacturers of amphetamine products (including Adderall) only sold approximately 70 percent of their allotted quotas in 2022. That meant that there were approximately 1 billion more doses that they could have produced but did not make or ship. At the time, the agencies said its 2023 data was trending in the same direction.

In 60 percent of cases, manufacturers do not know or do not provide reasons why their drugs fall into short supply, ASHP found.

The organization has put forth policy recommendations to prevent shortages and improve supply chains, advocating for federal and regulatory changes. “Much work remains to be done at the federal level to fix the root causes of drug shortages,” Abramowitz said. “ASHP will continue to engage with policymakers regularly as we guide efforts to draft and pass new legislation to address drug shortages and continue to strongly advocate on behalf of our members for solutions that work.”

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