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AbbVie, Lilly among leaders in next-generation blood cancer drugs at ASH meeting

A focus on new, targeted and durable blood cancer treatments at pharmaceutical giants, including AbbVie Inc., Regeneron Pharmaceuticals Inc. and Eli Lilly and Co., point to improved outcomes for patients with leukemia, lymphoma and myeloma, which can be difficult to treat or chronic.

Among about 40 abstracts AbbVie presented at the American Society of Hematology, known as ASH, the blood cancer drug Venclexta was the subject of more than half, showing the importance the company has placed on the treatment. Venclexta gained its first U.S. approval in 2016 for chronic lymphocytic leukemia, or CLL.

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Next-generation blood cancer drugs presented at the annual meeting of the American Society of Hematology held Dec. 5-8 have shown durability over time, increased safety and the ability to target patients with disease mutations.

Source: Pixabay

One of the studies of Venclexta, which AbbVie co-markets with Roche Holding AG, showed that the drug's benefit in CLL remained after three years off treatment, said AbbVie Executive Medical Director Venclexta Global Development Lead John Hayslip in an interview. Along with Roche's long-time cancer drug Rituxan in the study called Murano, patients showed minimal lasting disease five years after the start of the trial and three years after the final dosing.

"With previous analyses, we were very hopeful that the deep responses we were seeing would carry over or translate into impactful, durable remissions," Hayslip told S&P Global Market Intelligence. "It's very exciting as these data have matured to see that indeed that promise and that optimism is coming to fruition."

Hayslip said targeted therapies like Venclexta, which is among a class of drugs called Bcl-2 inhibitors, have led to major strides in treating blood cancers like leukemia.

"I've practiced when we didn't have targeted therapies in the era of chemotherapy," Hayslip said. "Clearly, as we developed these targeted therapies, it's important for patients who needed better options."

Venclexta is also now being used to treat patients with acute myeloid leukemia, with an October U.S. approval in the disease for older patients who cannot tolerate intense chemotherapy.

AbbVie and Roche are further working to expand the uses of Venclexta as they combine the drug with chemotherapies and other targeted treatments like Johnson & Johnson's Imbruvica.

"One area we've not touched on that shows the breadth of potential for Venclexta is in the multiple myeloma space," Hayslip said, adding that multiple myeloma patients with certain mutations show encouraging results with Venclexta. "It's rewarding to see across multiple hematologic malignancies the relevance of Bcl-2 inhibition and the effect that Venclexta can bring to patients."

Bispecifics vs. cell therapy

Fellow drugmaker Regeneron has focused on another group of therapies called bispecifics that have demonstrated usefulness after newer treatments like cell therapy have failed in certain patients with a kind of lymphoma.

Regeneron's odronextamab is a bispecific antibody in the class CD20 x CD3 that eliminated tumors in 70% of patients with follicular lymphoma in an early-stage study. The drug promotes T cells to kill tumors as a sort of ignition key, according to Andres Sirulnik, Regeneron's senior vice president of Translational & Clinical Sciences in Hematology.

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Regeneron's next step is to target bispecifics to certain tumor types and keep the T cells activated after the ignition, which Sirulnik said could revolutionize cancer treatment.

"Our next generation of bispecifics will look at maintaining that initial signal," Andres said. "It's like providing the gas with the pedal to further enhance that activation and also sustain that activation of the T cell."

Cell therapies — otherwise known as CAR-T therapies — are in-hospital procedures, whereas bispecifics can be provided off-the-shelf and adjusted over time.

"Once you introduce CAR-Ts, it is an all or nothing — you cannot take it back," Andres said.

Another of Regeneron's bispecific antibodies, called REGN5458, also showed a lasting response in patients with multiple myeloma in an early study.

'Best-in-class potential'

Lilly showcased early results from the BTK inhibitor Loxo-305 at ASH demonstrating that the drug slowed cancer in patients with lymphoma. Lilly acquired Loxo Oncology and its line of targeted cancer drugs in early 2019 for $8 billion.

Loxo-305 could someday be the best in its class of targeted blood cancer treatments based on the phase 1/2 study where more than half of patients showed reduced disease, Cantor Fitzgerald analyst Louise Chen said in a Dec. 6 note.

"Physicians we have spoken to are looking for next-generation [BTK inhibitors] like Loxo-305 to offer better safety (no bleeding or atrial fibrillation) and the ability to treat resistant patients," Chen said. "The durability of these treatments will be important, as well."

Lilly will eventually face off with Merck & Co. Inc., which is developing its own BTK inhibitor called MK-1026. This competition will be important to watch, according to Cowen analyst Steve Scala, but Loxo-305 still "has the potential to become the treatment of choice across lines of therapy."

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