ASH: AbbVie, Roche pad their case for fixed-duration Venclexta use in CLL

Venclexta
AbbVie is working to snag an approval for a combination of Venclexta and Imbruvica in the front-line chronic lymphocytic leukemia setting. (AbbVie)

ORLANDO, FLORIDA—AbbVie and Roche have been fielding their fair share of questions about how well a fixed-duration regimen of Venclexta and Rituxan can keep chronic lymphocytic leukemia (CLL) from returning after therapy ends. The companies now think they have some compelling answers.

The duo posted an 81% reduction in the risk of disease progression or death at the four-year treatment mark, topping a pairing of Rituxan and bendamustine, the partners said Sunday at the American Society of Hematology (ASH) annual meeting.

The drug combo also put up higher rates of minimal residual disease-negativity, a commonly used metric in CLL that measures the number of leukemia cells remaining in the body after treatment.

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In terms of extending lives, the Venclexta-Rituxan duo also cut the risk of death by 59%, and 68% of patients who received the combo were alive with their cancer still at bay 24 months after stopping therapy.

RELATED: AbbVie, Roche drive Venclexta toward $3B with Rituxan combo nod in CLL

The performance “really demonstrates that there is no dropoff,” even after an additional year off of treatment, said Rod Humerickhouse, asset strategy leader at AbbVie.

"That brings a lot of confidence and really answers that key question for us: ‘Yes, you can stop,'" Humerickhouse added, "and those patients … who have achieved deeper responses, they are doing extremely well and are going to benefit from long periods of treatment-free remission.”

In the past, that level of response—which Humerickhouse called “front-line-like”—was mostly reserved for “the young, fit patients who could get the more aggressive chemo” in the relapsed or refractory setting, he said. But now, it’s “almost universally available with a fixed-duration treatment.”

With those efficacy numbers in tow, AbbVie and Roche are looking at the combination’s fixed duration as a positive for patients who don’t want constant reminders of their disease.

“I was a practicing hematologist previously, and I would have preferred to treat my patients with something that would be completed in a year and would give them a really deep response,” Roche Senior Vice President Nancy Valente said. “They can return to their lives rather than be reminded every day by taking a pill that they still have cancer and still need cancer therapy.”

“You essentially have a period where your life is normal,” Humerickhouse added, and “I think that is quite meaningful."

"Then we can even begin to talk about the value or cost of therapy that we aren’t realizing at the patient level or for the healthcare system as a whole," he said. "Fixed duration does bring a real value to many stakeholders."

RELATED: AbbVie, Roche snag another CLL nod, this time for Venclexta-Gazyva

Of course, there are other options—and those include therapy with BTK inhibitor Imbruvica (ibrutinib), the blockbuster cancer-fighter AbbVie shares with Johnson & Johnson’s Janssen unit. That drug, in tandem with Rituxan and bendamustine, bears a green light in previously treated patients.

But AbbVie is also working to combine the two blood cancer stars to treat newly diagnosed patients. Saturday at ASH, the phase 2 Captivate study showed marrying Imbruvica and Venclexta could effectively clear disease in more than 70% of patients.

“Continuous ibrutinib therapy is still the standard of care. I don’t think that’s changed,” said Mark Wildgust, VP of global medical affairs for oncology at Janssen. But with the Captivate results, “If you’re looking to try to find a CLL cell in the patients’ blood or bone marrow, it’s just not there in three quarters of them.”

If those results hold up in phase 3 trials and the regimen eventually scores a regulatory go-ahead, patients and their doctors will have some decisions to make, said Danelle James, head of clinical science at AbbVie’s Pharmacyclics business.

“It’s hard to beat the continuous therapy with ibrutinib in terms of progression-free survival just because it is a regimen that’s really beat all the other standards of care right now,” she said. But “if the patient doesn’t want to necessarily be monitored with labs or following their white count—they just want all their disease completely away—that’s where the regimen will be most compelling.”

For now, the companies still have plenty of questions to answer, SVB Leerink analyst Andrew Berens wrote in a weekend note to clients. 

"Based on the data presented at the meeting, it is still unclear how many patients could stop treatment, and of those that discontinued the BTK regimen, whether their prognosis differed from the current standard of care, continuous BTK usage until progression," Berens said.

"We see the fixed-duration venetoclax regimen as primarily replacing the chemo-immunotherapy usage in CLL (FCR)," he said, "with BTK treatment remaining the cornerstone of frontline usage in the majority of patients, even without fixed-duration implementation."

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