Around this time six years ago, scientists from China's Legend Biotech landed at the annual meeting of the American Society of Clinical Oncologists (ASCO) with some truly impressive data that showed a 100% response rate in 35 multiple myeloma patients who received the company's CAR-T cell therapy candidate in an early-stage trial.
The small study garnered attention from the biggest pharma out there — J&J's Janssen — and by December the two locked arms for a long haul collaboration. Now, at the same conference, the companies are officially (after an initial data leak in April) presenting results from a phase 3 study of the cell therapy now called Carvykti, showing a 74% reduction in tumor progression or death in more than 400 patients with multiple myeloma.
"From Legend's perspective, we're very happy with how the partnership has evolved," Legend CEO Ying Huang said in an interview prior to ASCO.
The companies celebrated the first approval of Carvykti just last year for patients with four or more prior lines of therapy, and the new data is likely to allow for even earlier treatment, analysts say.
"It's been a win-win situation for Janssen and for Legend, but it's a great win also for patients because we were able to shepherd this asset from research stage to phase 1 to an FDA-approved commercial therapy in a mere four years," Ying said, adding that the company's U.S. operations grew from non-existent to more than 800 employees since the beginning of 2018.
For Janssen, the new data from the trial, which was called Cartitude-4, is an opportunity to reach more patients earlier in their disease progression, said Dr. Craig Tendler, the company's global head of late-stage clinical development in oncology.
"The key I take away from the unprecedented data coming out of Cartitude-4, and what is reinforcing our confidence, is the potential to redefine the treatment landscape across all lines of therapy in multiple myeloma," Tendler said.
The two companies have worked hand-in-hand to bring Carvykti to where it stands today, and both Ying and Tendler expressed how they owe so much to one another in realizing the potential of the cell therapy from the early stages.
The power of partnership
So often, collaboration is seen as the lifeblood of the biopharma construct — a small biotech with limited funds and a risky bet on a novel compound links up with a Big Pharma benefactor that can provide the cash runway, and regulatory and commercial expertise to bring a treatment to patients. The gamble doesn't always pay off, but in the case of Janssen and Legend, the fruits of their labor are just beginning to emerge.
"It's a great example of a biotech company having a very novel technology and approach to addressing this problem — we were at the beginning very much intrigued by how they designed their B cell maturation agent (BCMA) CAR-T using two binding domains to the target," Tendler said. "When they shared the preliminary data, we already saw evidence that this was going to be differentiated from other BCMA CAR-Ts in myeloma."
For their part, Janssen could give Legend the window to make Carvykti possible as an approved therapy in only a handful of years.
"They saw in us a real commitment to accelerate the development of Carvykti across all stages of myeloma and to make the early investments to join teams that would put together the best comprehensive development program — to essentially take their baby and work with it in a collaborative way that would get the best out of it," Tendler said.
"It is indeed 100% personalized medicine and it shows you the power of science."
CEO, Legend Biotech
The collaboration has paid off in other ways, as well. J&J reported $55 million in revenue from Carvykti in the fourth quarter of 2022, growing to $72 million in the first quarter of this year. And Ying said that, on the manufacturing side, the companies are on track to exit 2025 with global capacity to produce more than 10,000 doses per year.
Specifically, J&J has set its sights on $60 billion in annual pharma revenue by 2025, and forecasted peak annual sales of Carvykti at more than $5 billion would be a boon to help get them there, said Cantor Fitzgerald analyst Louise Chen in April when the Cartitude-4 results were leaked online. And with physicians expressing that they would want to give their patients the therapy even earlier in their treatment plan, Chen said there is a large market opportunity.
Earlier this year, Bristol Myers Squibb released phase 3 data for its rival multiple myeloma CAR-T cell therapy Abecma, showing that the treatment reduced the risk of disease progression or death by 51% — a good deal short of Carvykti's 74%. Although there were key differences in the trials, including the number of previous treatments patients had received, the results place Carvykti in the lead in the eyes of many analysts.
The art of precision
Personalized medicine has been the lofty goal of the pharma industry for decades. And autologous therapies like Carvykti, which use a patient's own cells to fight cancer, bring the concept to reality.
"When I was in grad school a few years back, we talked about so-called personalized medicine because everybody's genes are slightly different — the way cancer cells grow could be driven by different drivers or proteins or growth factors," Ying said. "Today, that is reality because all six commercially available CAR-T therapies today are autologous medicines — it is indeed 100% personalized medicine and it shows you the power of science and how personalized medicine can actually work to effectively treat cancer."
The concept of personalized treatments has come a long way in just a single career, Tendler said.
"We started to think about precision medicine in a very narrow way 20 some-odd years ago with Gleevec (from Novartis for chronic myelogenous leukemia) and we thought we'd never have that kind of situation again — and for the most part we don't when it comes to small-molecule targeting of single driver pathways," Tendler said. "But now, with being able to harness the immune system, we're able to do that in a very potent way, in a very selective way, and more safely than ever."
Tendler said that Cartitude-4 shows improved safety for Carvykti compared to earlier studies that were already the basis for the first approval. CAR-Ts often bring about a concern for immune-related side effects such as cytokine release syndrome.
And still, CAR-Ts are subject to long wait times and restricted patient access due to the nature of the manufacturing process — removing cells from a patient, sending them to a facility where they are engineered using the cell therapy process, and then delivering back to the patient. But with the power of Janssen and Legend combined, Ying said these barriers are becoming easier to overcome.
"It's different in terms of how we manufacture this medicine, and it's very complicated and capital-intensive," Ying said. "As a partnership, we've invested tremendously in the supply chain operation, and our goal is to ensure very reliable supply for patients who need this therapy — that includes expanding our lentivirus supply, introducing new manufacturing solutions and investing in our global footprint."