Acalabrutinib

AstraZeneca says it plans to participate in the next round of Medicare negotiations under the Inflation Reduction Act. But this time around, the company says it’s dealing with a whole different set of considerations, from a new administration to a product with longer patent life. AstraZeneca’s blood cancer drug Calquence is among the next 15 drugs subject to IRA negotiations. It’s one of the company’s top sellers in oncology, generating $2.5 billion in 2023. And it’s “still got plenty of life left on the patent,” David Fredrickson, executive VP of AstraZeneca’s oncology business unit, told Endpoints News in an interview. Many of the drugs selected for the government’s first round of negotiations were “at the end of their life cycle,” Fredrickson said. That includes AstraZeneca’s diabetes drug Farxiga, which has patents expiring as soon as this year. Patent expiration was one of the reasons why some pharma companies suggested early on that the IRA’s impact would be modest, as impending generic competition was already expected to affect sales. But in the second round, Fredrickson said “we’re seeing more that are still in their median stages of the life cycle, like Calquence.” Calquence is covered by a range of patents, some of which don’t expire until 2036, according to the FDA’s database of approved drugs. Other drugs on the list also have some patents extending into the 2030s, such as Teva’s Austedo and Novo Nordisk’s semaglutide products. “Calquence remains an important innovation that should be under protection for the foreseeable number of years in front of us,” Fredrickson said. An AstraZeneca spokesperson confirmed to Endpoints that the company plans to participate in the next round of negotiations. Drugmakers have until the end of February to decide if they are participating. When asked what lessons AstraZeneca may take from its first round of negotiations for Farxiga, Fredrickson said, “We haven’t learned that much about how oncology medicines are going to go through the price setting.” Roughly a fourth of all drugs selected for this cycle treat cancer, as opposed to just one in the first cycle. Nevertheless, Fredrickson said AstraZeneca is “absolutely confident” in ambitions it laid out last May to reach $80 billion in total revenue by 2030. “Oncology is a critical component of that, and there’s nothing that has happened in this that is changing our view,” he said. Weighing legal options Fredrickson declined to comment on how AstraZeneca’s legal strategy might change now that Calquence has been selected for the next round of negotiations. The company’s initial court challenge fell flat last year in federal district court, and is now being argued in the Third Circuit Court of Appeals. “As part of that effort from last year, we will also determine how, if at all, we want to now incorporate this latest set of news from Friday on Calquence,” Fredrickson said. However, Fredrickson added that AstraZeneca believes Calquence should not be eligible for negotiations, and said he wants CMS to reconsider. While current guidance states that small molecules have seven years post-approval and biologics have 11 years before they become eligible to be selected for negotiations, AstraZeneca told Endpoints that a new Calquence tablet formulation approved in 2022 should have reset the clock. “We were hopeful that the innovations that we’ve been pursuing throughout the life cycle of Calquence would have actually resulted in CMS taking a different position. And we would urge them to reconsider,” Fredrickson said. While Fredrickson said he “can’t speculate on the administration’s intentions with IRA,” he added that he hopes “cancer is a national policy priority for the United States for the next four years.”

Recently, AstraZeneca announced that its BTK inhibitor, Calquence (acalbrutinib), has received FDA approval for a new indication. It is now authorized for use in combination with bendamustine and rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are not suitable for autologous stem cell transplantation. This approval marks Calquence as the first BTK inhibitor approved for first-line therapy in MCL. Approval Based on Positive Clinical Results The FDA's decision was primarily based on positive outcomes from a Phase III clinical trial assessing Calquence in combination with standard treatment (SOC: bendamustine + rituximab). The study evaluated the efficacy and safety of this regimen in MCL patients aged 65 years or older who had not received prior treatment. The trial's main endpoint was progression-free survival (PFS). Results indicated that patients receiving Calquence experienced a statistically and clinically significant improvement in PFS compared to the SOC group, with median PFS durations of 66.4 months versus 49.6 months (HR=0.73, P=0.0160). Additionally, there was a positive trend toward improved overall survival (OS) in the Calquence group (HR=0.86, P=0.27). Overview of MCL and BTK Inhibitors MCL is a rare form of B-cell non-Hodgkin lymphoma characterized by both indolent and aggressive clinical-pathological features. Over the past decade, several new therapies have been developed for MCL, particularly Bruton’s tyrosine kinase inhibitors (BTKis), which have demonstrated significant efficacy in treating these patients. Currently, five BTK inhibitors are available globally for MCL treatment: the first-generation ibrutinib and the second-generation agents acalbrutinib, zanubrutinib, obuibrutinib, and the non-covalent BTK inhibitor pirtobrutinib. Calquence has gained a competitive edge as it becomes the first approved BTK inhibitor for first-line treatment in MCL. Its main competitor, BeiGene's zanubrutinib, is still in Phase III trials for first-line MCL treatment. Ibrutinib has shown a median PFS benefit of nearly 28 months, which is significantly higher than the 17 months observed for acalbrutinib in the ECHO trial. However, despite its success in PFS, ibrutinib has not translated this benefit into improved overall survival, preventing its approval for first-line therapy. AstraZeneca's Calquence approval represents a significant advancement in the treatment landscape for MCL, offering a new option for patients who cannot undergo stem cell transplantation. With its proven efficacy in a clinical setting, Calquence is poised to play a crucial role in the management of this challenging disease, further establishing its position in the evolving field of oncology.