Novartis International AG / Novartis announces positive top-line results from ASCEND-4, a Phase III trial of Zykadia® in untreated adult ALK+ NSCLC patients . Processed and transmitted by Nasdaq Corporate Solutions. The issuer is solely responsible for the content of this announcement.
- In a Phase III clinical study, Zykadia® extended progression-free survival (PFS) when compared with standard chemotherapy, including maintenance
- Novartis is moving forward with global regulatory submissions for this indication; full results will be presented at an upcoming medical congress
Basel, September 23, 2016 - Novartis today announced top-line results from its Phase III ASCEND-4 clinical study for Zykadia® (ceritinib) in patients with advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). The multicenter, randomized trial (NCT01828099), which assessed the efficacy and safety of Zykadia in previously untreated adult patients, met its primary endpoint, demonstrating clinically significant improvement in progression free survival (PFS) compared to standard chemotherapy, including maintenance.
In addition to PFS, clinically meaningful results were achieved across key secondary efficacy measures, including objective response rate (ORR) and duration of response (DoR). The adverse events observed were consistent with the previously known adverse event profile of Zykadia. A full analysis of ASCEND-4 data along with detailed efficacy and safety results will be submitted for presentation at a major medical congress.
"Zykadia has proven to be an important treatment option for ALK+ NSCLC patients who have progressed following treatment with crizotinib," said Alessandro Riva, Global Head, Oncology Development and Medical Affairs, Novartis Oncology. "We are pleased to see these topline results show promise in untreated patients with advanced disease, and look forward to sharing these data with regulatory authorities in the coming months."
Of more than 1.8 million lung cancer diagnoses each year, approximately 2-7% of cases have the ALK gene rearrangement,. These patients are candidates for treatment with a targeted ALK inhibitor.
ASCEND-4 was a Phase III randomized, open label, multicenter global clinical trial to evaluate the safety and efficacy of Zykadia compared to standard chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK+ NSCLC who received no prior therapy for their advanced disease.
The study was conducted at 203 clinical trial sites globally across 31 countries and randomized across 376 patients. Patients received Zykadia orally at 750 mg/daily or standard pemetrexed based platinum doublet chemotherapy per label (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5-6) including pemetrexed maintenance.
The primary endpoint of the trial was PFS by blinded independent review committee. Key secondary endpoints included: overall survival, PFS by investigator assessment, overall response rate, duration of response, disease control rate and time to response.
Zykadia is an oral, selective inhibitor of anaplastic lymphoma kinase (ALK), a gene that can fuse with others to form an abnormal "fusion protein" that promotes the development and growth of certain tumors in cancers including non-small cell lung cancer (NSCLC). Zykadia was granted conditional approval in the EU for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib. In the US, Zykadia was granted accelerated approval for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. Zykadia is currently approved in over 55 countries worldwide. Please visit www.NovartisOncology.com/news/product-portfolio/zykadia for additional information.
Zykadia Important Safety Information
Zykadia may cause serious side effects.
Zykadia may cause stomach upset and intestinal problems in most patients, including diarrhea, nausea, vomiting and stomach-area pain. These problems can be severe. Patients should follow their doctor's instructions about taking medicines to help these symptoms, and should call their doctor for advice if symptoms are severe or do not go away.
Zykadia may cause severe liver injury. Patients should have blood tests prior to the start of treatment with Zykadia, every two weeks for the first month of treatment and monthly thereafter, and should talk to their doctor right away if they experience any of the following symptoms: tiredness (fatigue), itchy skin, yellowing of the skin or the whites of the eyes, nausea or vomiting, decreased appetite, pain on the right side of the abdomen, urine turns dark or brown, or bleeding or bruising more easily than normal.
Zykadia may cause severe or life-threatening swelling (inflammation) of the lungs during treatment that can lead to death. Symptoms may be similar to those symptoms from lung cancer. Patients should tell their doctor right away about any new or worsening symptoms, including trouble breathing or shortness of breath, fever, cough, with or without mucous, or chest pain.
Zykadia may cause very slow, very fast, or abnormal heartbeats. Doctors should check their patient's heart during treatment with Zykadia. Patients should tell their doctor right away if they feel new chest pain or discomfort, dizziness or lightheadedness, faint, or have abnormal heartbeats, blue discoloration of lips, shortness of breath, swelling of lower limbs or skin, or if they start to take or have any changes in heart or blood pressure medicines.
Zykadia may cause high levels of glucose in the blood. People who have diabetes or glucose intolerance, or who take a corticosteroid medicine have an increased risk of high blood sugar with Zykadia. Patients should have glucose blood tests prior to the start of treatment with Zykadia and during treatment. Patients should follow their doctor's instructions about blood sugar monitoring and call their doctor right away with any symptoms of high blood sugar, including increased thirst and/or urinating often.
Zykadia may cause high levels of pancreatic enzymes in the blood and may cause pancreatitis. Patients should have blood tests prior to the start of treatment with Zykadia and as needed during their treatment with Zykadia. Patients should talk to their doctor if they experience signs and symptoms of pancreatitis which including upper abdominal pain that may spread to the back and get worse with eating.
Before patients take Zykadia, they should tell their doctor about all medical conditions, including liver problems; diabetes or high blood sugar; heart problems, including a condition called long QT syndrome; if they are pregnant, if they think they may be pregnant, or if they plan to become pregnant; are breastfeeding or plan to breastfeed.
Zykadia may harm unborn babies. Women who are able to become pregnant must use a highly effective method of birth control (contraception) during treatment with Zykadia and up to 3 months after stopping Zykadia. It is not known if Zykadia passes into breast milk. Patients and their doctor should decide whether to take Zykadia or breastfeed, but should not do both.
Patients should tell their doctor about medicines they take, including prescription medicines, over-the-counter medicines, vitamins and herbal supplements. If they take Zykadia while using oral contraceptives, the oral contraceptives may become ineffective.
The most common adverse reactions with an incidence of >=10% were diarrhea, nausea, vomiting, tiredness (fatigue), liver laboratory test abnormalities (requires blood test monitoring), abdominal pain, decreased appetite, constipation, rash, kidney laboratory test abnormalities (requires blood test monitoring), heartburn and anemia. Grade 3-4 adverse reactions with an incidence of >=5% were liver laboratory test abnormalities, tiredness (fatigue), diarrhea, nausea and hyperglycemia (requires blood test monitoring).
Patients should stop taking Zykadia and seek medical help immediately if they experience any of the following, which may be signs of an allergic reaction:
- Difficulty in breathing or swallowing
- Swelling of the face, lips, tongue or throat
- Severe itching of the skin, with a red rash or raised bumps
Patients should tell their doctor of any side effect that bothers them or does not go away. These are not all of the possible side effects of Zykadia. For more information, patients should ask their doctor or pharmacist.
Patients should take Zykadia exactly as their health care provider tells them. Patients should not change their dose or stop taking Zykadia unless their health care provider advises them to. Zykadia should be taken once a day on an empty stomach. Patients should not eat for at least 2 hours before and 2 hours after taking Zykadia. If a dose of Zykadia is missed, they should take it as soon as they remember. If their next dose is due within the next 12 hours, they should skip the missed dose and take the next dose at their regular time. They should not take a double dose to make up for a forgotten dose. Patients should not drink grapefruit juice or eat grapefruit during treatment with Zykadia, as it may make the amount of Zykadia in their blood increase to a harmful level. If patients have to vomit after swallowing Zykadia capsules, they should not take more capsules until their next scheduled dose.
Please see full Prescribing Information for Zykadia.
The foregoing release contains forward-looking statements that can be identified by words such as "moving forward," "will," "upcoming," "show promise," "look forward," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Zykadia, or regarding potential future revenues from Zykadia. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management 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 Zykadia will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Zykadia will receive additional regulatory approvals or be commercially successful in the future. In particular, management's expectations regarding Zykadia could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit http://www.novartis.com.
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 International Cancer Control: Global Cancer Statistics. Centers for Disease Control and Prevention Website. http://www.cdc.gov/cancer/international/statistics.htm. Last updated February 2015.
 National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung Cancer. NCCN 2014 3:1-148.
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