ESMO: GLP-1s have taken over the cultural zeitgeist. 33,000 oncologists have something to say about that

If you’ve been living under a rock for the past several years, you probably still know what a GLP-1 inhibitor is—at least by brand name. But the 33,000 attendees at the European Society for Medical Oncology Congress would like to remind you that there’s plenty of breakthroughs in cancer worthy of the same kind of fanfare.

“In biopharma, there's always a bit of a herd effect, for lack of a better phrase,” said Charlie Fuchs, senior vice president and global head of oncology and hematology drug development at Genentech and Roche. “Having been involved in some of the work in GLP-1 and the incretins, it's exciting … and I'm sure when potential companies see the returns on that, it's impressive.

“Does that discount the value of investing in hematology? Oncology? No,” he said.

Eli Lilly has an interesting perspective, being one of the two main leaders in the diabetes and obesity space thanks to Mounjaro. The GIP and GLP-1 receptor agonist has been approved for diabetes but has also been used off label for weight loss. The Indianapolis pharma is awaiting an FDA nod to treat adults with obesity or who are overweight, too. 

“The innovation that's taken place in the context of diabetes and chronic weight management is probably one of the biggest public health impacts that we will ever see in our lifetimes,” Jacob Van Naarden, president of Loxo@Lilly, said in an interview. The other major advancement being the collective movement to address the COVID-19 pandemic, he noted. In fact, Van Naarden puts the new weight management and diabetes drugs on the same pillar as the smallpox or polio vaccines.

The therapies mimic a hormone called glucagon-like peptide 1, stimulating the body to produce more insulin as the blood sugar rises after a person eats. The extra insulin lowers blood sugar, which can control type 2 diabetes. Researchers are still working through how the drug class contributes to weight loss, but it's believed that hunger is reduced and the movement of food from the stomach may be slowed. This means a person may feel full faster and for longer.  

“I think we will look back at this and say this was one of the biggest public health impacts of medicine ever, given the burden of these diseases globally and the downstream diseases that result from obesity, the cost to society and people living with these diseases,” Van Naarden said. “I actually don't think we've yet even appreciated the effect.”

While GLP-1s have made it into the cultural zeitgeist—way beyond the trade publications (including yours truly) that traditionally trumpet such medical breakthroughs—Van Naarden says, “I would actually almost say it's not getting enough attention.”

poster presentations ESMO 2023
People gather to read the latest poster presentations during the ESMO Congress in Madrid. (Annalee Armstrong/Fierce Biotech)

With that said, Van Naarden admits that some of the fanfare around GLP-1 therapies has been somewhat negative, with an intense focus in Hollywood on weight loss or dieting. But he can draw a straight line to oncology and other chronic obesity issues.

“It's just the wrong frame, just to be perfectly honest. These are not weight loss drugs. These drugs improve people's health,” Van Naarden said.

GLP-1s could ultimately prove to reduce obesity-related cancers, but that kind of research will take time, and Van Naarden isn't even sure if a clinical trial could be designed to show that. He said the conversation overall needs to shift to how GLP-1s can address conditions like sleep apnea, osteoarthritis, kidney outcomes, cardiovascular benefits and more, all of which can be consequences of obesity, which he says is itself a very real disease.

And GLP-1s and oncology do not have to compete for attention, Van Naarden and Fuchs agree. There’s plenty of exciting things happening in cancer research—as evidenced by the thousands of enthusiastic attendees who flocked to Madrid in October to hear the latest science.

Van Naarden added, with a laugh: “Certainly from a global public health perspective, I think that the impact factor is legitimately higher with what’s going on with incretins … I'll get off my soapbox on that.”


On to the oncology soapbox

The need in oncology has not gone away and likely won’t, despite pharma’s best efforts. According to Fuchs, the incidence and mortality related to cancer in the U.S. and globally is rising as the population ages, due to exposure, diet and lifestyle.

“The plurality of investment in biotechnology remains cancer,” Fuchs said. “The truth is, if you look at it from a purely business standpoint, if you invest in and develop an effective cancer therapy, there's a reasonable return on investment.”

Oncology trials can take longer than other therapy areas, increasing the investment and time to a potential approval. The average cancer study took about 11.6 years, 30 to 40% longer than therapies for other conditions, according to a February report from Deloitte (PDF). Central nervous system drugs took 6.5 years while infectious diseases took about 4.3 years.

And yet, oncology remains the most active area of drug development, according to the report. Cancer drugs represented about 36% of the entire pharmaceutical pipeline between 2013 and 2022, Deloitte found.

ESMO produced some truly exciting data. Seagen and Astellas’ antibody-drug conjugate Padcev plus Merck & Co.’s Keytruda received a prolonged standing ovation after data was presented showing the combo reduced the risk of death by 53% compared to chemo in patients with previously untreated bladder cancer.

For Novartis, the future of cancer care is advancing breakthrough therapies into earlier lines of treatment to allow patients to not only live longer, but live better, without the risk of reoccurrence. Jeff Legos, Ph.D., head of global oncology and hematology at Novartis, points to phase 3 results from the Swiss pharma’s NATALEE study of Kisqali in early breast cancer. The standard of care for patients with stage II or III HR+/HER2- early breast cancer at risk of recurrence is surgery. But since their cancer is likely to come back, chemotherapy with or without radiotherapy is the next step, Legos said.

“[Kisqali] may potentially provide a new therapeutic option where patients can live longer, live well and live without the risk of cancer recurrence,” Legos said.

Novartis has also collected data that the CDK4/6 inhibitor has the highest quality of life benefit.

“If you think about a woman or a man who has to make a choice between pursuing and doing everything they can to potentially prevent the risk of recurrence or saying, ‘You know what, I'm worried that my quality of life is going to be potentially disrupted if I do X, Y or Z,’” Legos said. “Kisqali hopefully will afford patients the opportunity to be able to do both.”

Van Naarden similarly is excited to see the industry moving innovative therapies earlier in the course of treatment, which he says can have an impact on delaying disease progression. Lilly presented data at ESMO on Verzenio showing just that in breast cancer, he noted.

Over at Merck & Co., excitement is building over the cancer vaccine collaboration with Moderna. The companies are testing V940 in lung cancer and melanoma in combination with Keytruda.

“It's an example of something that I see as a potential emerging therapy that, should this be confirmed in phase 3 trials, could be a real game changer in oncology and could really change what's possible and how we treat patients,” Merck’s Jane Healy, M.D., Ph.D., said in an interview at ESMO.

In phase 2, the vaccine in combo with Keytruda reduced the risk of recurrence or death by 44% compared with Keytruda alone for the adjuvant, or post-surgery, treatment of resectable melanoma. The partners have since advanced into a phase 3 study called V940-001 for post-surgery treatment of patients with resected melanoma that’s at high risk of recurrence. The vaccine is made by profiling each patient’s tumor mutational signature and is designed to induce an immune response against the corresponding antigens.

Another needed advancement in cancer care is simply catching the disease earlier through effective screening tools, according to Van Naarden. This is particularly important in breast and colon cancer.

The industry will continue to get better at prolonging progression-free survival and overall survival, but Van Naarden said that the reality is patients with solid tumors are likely to die from their disease eventually. At the end of the day, that's why pharma needs to keep pushing to advance oncology research. 

“I want Lilly’s and our industry’s efforts to prolong that as much as possible,” Van Naarden said.

To read more of Fierce Biotech's coverage of the ESMO Congress, click here. Fierce Pharma's coverage is available here.