Ad hoc announcement pursuant to Art. 53 LR 


   -- CANOPY-1 Phase III study did not meet its primary endpoints of overall 
      survival (OS) and progression-free survival (PFS) in patients with 
      previously untreated locally advanced or metastatic non-small cell lung 
      cancer (NSCLC)1 
 
   -- Potentially clinically meaningful improvements in both PFS and OS were 
      observed among pre-specified subgroups of patients with inflammatory 
      biomarkers; additional analyses are ongoing1 
 
   -- Results support continued study of canakinumab in earlier stages of lung 
      cancer, as potential adjuvant and neoadjuvant therapies, and further 
      evaluation of Pro-Tumor Inflammation in all lung cancer settings1 
 
   -- Patients in the CANOPY-A study more closely reflect the earlier CANTOS 
      study population than those in the CANOPY-1 trial2,3,4; CANTOS was the 
      first study to suggest that the inhibition of interleukin-1beta 
      (IL-1) may play a role in lung cancer3 
 
   -- Canakinumab showed no unexpected safety signals when combined with 
      pembrolizumab plus platinum-based chemotherapy

Basel, October 25, 2021 -- Novartis announced today that the CANOPY-1 Phase III study did not demonstrate the statistically significant primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients treated with canakinumab (ACZ885) combined with pembrolizumab plus platinum-based doublet chemotherapy, compared to patients receiving placebo in combination with pembrolizumab plus platinum-based doublet chemotherapy(1) . The trial data, however, showed potentially clinically meaningful improvements in both PFS and OS in pre-specified subgroups of patients based on the baseline inflammatory biomarker, hs-CRP, as well as other biomarker-defined subgroups. These data support further evaluation of canakunimab in lung cancer.

"CANOPY-1 provides critical insights into the treatment of this devastating disease, and we will continue to analyze the data and conclusions, as well as their potential clinical implications," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "While this trial did not confirm the benefit for all patients we hoped for, we are energized by the overall CANOPY-1 findings as they support our commitment to continue studying canakinumab in lung cancer. We share our gratitude and thanks to the CANOPY-1 study patients and clinical investigators for their partnership."

Novartis and investigators are collaborating on further data analysis and will present the full dataset at an upcoming medical meeting. The company is continuing with the evaluation of canakinumab in lung cancer, and is applying findings to the overall lung cancer development plan.

The comprehensive CANOPY clinical trial program continues with CANOPY-A, a Phase III study investigating canakinumab as an adjuvant therapy (after surgery)(2) , and CANOPY-N, a Phase II study in the neoadjuvant setting (before surgery)(5) . Enrollment for both trials is ongoing(2,) (5) . Patients in the CANOPY-A trial more closely reflect the earlier CANTOS study population than those in the CANOPY-1 trial(2) (,) (3) (,) (4) . CANTOS was the first study to show that blocking the IL-1 inflammatory signal may potentially reduce lung cancer's incidence and mortality(3) .

Canakinumab is a potential first-in-class interleukin-1beta (IL-1) inhibitor of the Pro-Tumor Inflammation (PTI) pathway in NSCLC(6) . PTI, which enables tumor development by driving cancer-causing processes and suppressing anti-tumor immune responses, is one of the potential hallmarks of cancer and targets in NSCLC(3) (,) (6) . Novartis is developing other potential PTI pathway inhibitors, which are at various stages of development, including gevokizumab(7) (,) (8) .

About canakinumab (ACZ885)

Canakinumab is a human monoclonal antibody that binds with high affinity and selectivity to human interleukin-1beta (IL-1) and neutralizes IL-1 activity by blocking its interaction with its receptors(9) (, ) (10) . By neutralizing IL-1, preliminary evidence suggests that canakinumab may inhibit Pro-Tumor Inflammation (PTI) to 1) enhance anti-tumor immune response; 2) reduce tumor cell proliferation, survival, and invasiveness; and 3) impair angiogenesis(11) . PTI enables tumor development by driving cancer-causing processes and suppressing anti-tumor immune responses(3) (,) (6) . Canakinumab is a potential first-in-class IL-1 inhibitor of the PTI pathway in NSCLC(6) .

About the CANOPY program

Novartis launched the CANOPY study program after observing significantly lower than expected rates of lung cancer mortality among patients in the Phase III cardiovascular CANTOS trial. The CANTOS trial evaluated canakinumab as a secondary prevention measure for cardiovascular events in patients following a heart attack(3) (,) (11) . Patients in the CANTOS trial also were at high risk for inflammatory cancers, like lung cancer, due to advanced age, smoking history, and other clinical risk factors(3) (,) (11) . Based on these findings, Novartis launched three large-scale, randomized, Phase III clinical trials and a Phase II clinical trial to investigate canakinumab as a potential treatment option in non-small cell lung cancer (NSCLC). 


   -- CANOPY-A (NCT03447769) is a double-blind, placebo-controlled Phase III 
      trial studying canakinumab in the adjuvant setting following surgical 
      resection and cisplatin-based chemotherapy, if required2. The adjuvant 
      study is designed to determine if treatment with canakinumab can prevent 
      cancer relapse2. 
 
   -- CANOPY-N (NCT03968419) is a Phase II neoadjuvant trial evaluating 
      canakinumab either as monotherapy or in combination with pembrolizumab 
      among patients with resectable NSCLC prior to their planned surgery5. 
 
   -- CANOPY-1 (NCT03631199) was a double-blind, placebo-controlled Phase III 
      trial evaluating canakinumab as a first-line treatment for locally 
      advanced or metastatic NSCLC in combination with pembrolizumab and 
      platinum-based doublet chemotherapy4. As reported today, the trial did 
      not met its primary endpoints of overall survival (OS) and 
      progression-free survival (PFS)1. 
 
   -- CANOPY-2 (NCT03626545) was a double-blind, placebo-controlled Phase III 
      trial investigating the role of canakinumab in combination with the 
      chemotherapy agent docetaxel in second- or third-line therapy 
      versus docetaxel alone in NSCLC12. In March 2021, Novartis announced that 
      the trial did not meet its primary endpoint, and data were presented at 
      the European Society of Medical Oncology (ESMO) 2021 Congress13.

Novartis and lung cancer

Lung cancer is one of the most common cancers worldwide, accounting for more than 2 million new cases diagnosed each year(14) . More people die of lung cancer every year than any other cancer(14) . There are two main types of lung cancer--small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)(15) . NSCLC accounts for approximately 85% of lung cancer diagnoses(14) (,) (16) .

Novartis is committed to working with the scientific and medical communities to reimagine the treatment of lung cancer and pursue advances in medicine that could extend the survival of people living with lung cancer. With one of the most diverse lung cancer development programs in the industry, Novartis is: developing experimental therapies that block cancer growth; learning more about ways to activate the body's immune system; increasing understanding of the relationship between chronic inflammation and tumor growth and progression; and exploring the potential for advanced nuclear medicine to fight the disease. As part of this continuing and broad commitment to targeting lung cancer, data from CANOPY-1 will be evaluated and used to inform canakinumab's future development program, including potential combination studies with tislelizumab.

Disclaimer

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "could," "expect," "committed," "investigational," "continues," "ongoing," "exploring," "to develop," "potentially," "hope," "investigating," "enables," "to determine," "evaluating," "committed," "developing," "learning," "continuing," "commitment," "further evaluation," "collaborating," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for canakinumab alone or in combination with other treatments, or regarding potential future revenues from canakinumab alone or in combination with other treatments. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events,and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that canakinumab, alone or in combination with other treatments, will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that canakinumab, alone or in combination with other treatments, will be commercially successful in the future. In particular, our expectations regarding canakinumab, alone or in combination with other treatments, could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing

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October 25, 2021 01:15 ET (05:15 GMT)