Products

* On May 22, 2014, the CHMP confirmed the refusal of the marketing authorisation for Reasanz® intended for the treatment of acute heart failure.On 23 January 2014, the Committee has already adopted a negative opinion, recommending the refusal of the marketing authorisation for this product. After considering the grounds for Novartis' request, the CHMP re-examined the initial opinion. At the time of the initial evaluation, the CHMP noted that the study results did not demonstrate a benefit for short-term relief of dyspnoea over up to 24 hours, and although some benefit was shown over 5 days it was not clear how this was of clinical relevance. Furthermore, the Committee had concerns about the way the effectiveness of the medicine in the study had been analysed. The results included assigned values for a number of patients who had died or had required additional treatment for worsening symptoms and whose actual data were not used. In addition, the CHMP questioned whether the type of the background treatment given to patients in the two study groups might have influenced the results. Since only one main study was included in the application, the CHMP concluded that further studies would be needed to confirm the effectiveness of Reasanz in the treatment of acute heart failure. During the re-examination, the CHMP reviewed again the data from the only main study submitted and confirmed its opinion that the effectiveness of Reasanz had not been sufficiently demonstrated. Therefore, although the safety of Reasanz seemed acceptable, the CHMP concluded that the benefits of Reasanz® did not outweigh its risks and maintained its previous recommendation that the medicine be refused marketing authorisation.

* On May 16, 2014, Novartis announced that the FDA has issued complete response letter for RLX030 (serelaxin) for the treatment of acute heart failure (AHF), stating that further evidence on the efficacy of RLX030 is required for a US license to be granted. The RLX030 submission to the FDA included phase II and III efficacy and safety data from the clinical development program, including the pivotal phase III RELAX-AHF study. Novartis is continuing to expand the data supporting the efficacy of RLX030 in acute heart failure with an extensive global clinical program, including the RELAX-AHF-2 trial which will enroll over 6,300 patients. Novartis intends to resubmit NDA with additional data when available

* On March 27, 2014, Novartis has announced that the FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted against approval for RLX030 (serelaxin) for the treatment of acute heart failure (AHF). Data presented at the Advisory Committee meeting included phase II and III efficacy and safety data from the RLX030 clinical development program, including the pivotal phase III RELAX-AHF study. In this study RLX030 improved the symptoms of acute heart failure (AHF) through reducing the rate of worsening heart failure, a measure of symptom deterioration that requires intensification of therapy."Recognizing the urgent patient need, today we presented what we believe to be a persuasive picture of the evidence for RLX030 so far - compelling results from our Phase II and III trials with no significant safety concerns," said Tim Wright, Global Head of Development, Novartis Pharmaceuticals. "The discussion provided important information that we will address with the FDA as it completes its review. In the meantime we'll continue to drive our robust clinical trial program and build upon the already established body of evidence."

* On January 24, 2014, Novartis has announced it will shortly submit a revised filing package, including new data analyses, for re-examination for conditional approval of RLX030 (serelaxin) for acute heart failure by the Committee for Medicinal Products for Human Use (CHMP) following a negative opinion issued. In accordance with CHMP process a revised opinion could be granted in Q2 2014. The file for regulatory approval is continuing review by the FDA in the United States where RLX030 was granted Breakthrough Therapy designation status in June 2013. On February 13th Novartis will present RLX030 efficacy and safety data at the FDA's Cardiovascular and Renal Drugs Advisory Committee meeting to discuss potential US approval. Reviews are also underway with health authorities in 16 countries around the world. In September 2013 the second phase III study RELAX-AHF-2 started recruitment of the over 6000 patients who are expected to be enrolled. The goal is to replicate the key findings of RELAX-AHF and the study will assess cardiovascular mortality as the primary endpoint. This would be one of the largest and most robust programs undertaken by a company for an AHF drug.

* On 23 January 2014, the Committee for Medicinal Products for Human Use (CHMP) has adopted a negative opinion, recommending the refusal of the marketing authorisation for Reasanz®, intended for the treatment of acute heart failure. The effects of Reasanz® were first tested in experimental models before being studied in humans. Novartis presented the results of one main study involving 1,161 patients with an episode of acute heart failure. Reasanz® infusion was compared with placebo (a dummy treatment) as an addition to their other treatment. The main measure of effectiveness was the extent to which dyspnoea (shortness of breath) was relieved, measured short-term (after 6, 12 and 24 hours) and over 5 days. The CHMP noted that the study results did not demonstrate a benefit for short-term relief of dyspnoea over up to 24 hours, and although some benefit was shown over 5 days it was not clear how this was of clinical relevance. Furthermore, the Committee had concerns about the way the effectiveness of the medicine in the study had been analysed. The results included calculated values  for a number of patients who had died or had required additional treatment for worsening symptoms and whose actual data were not used. In addition, the CHMP questioned whether differences in the background treatment given to patients in the two study groups may have influenced the results. Since only one main study was included in the application, further studies would be needed to confirm the effectiveness of Reasanz in the treatment of acute heart failure. Although the safety of Reasanz® seemed acceptable, in view of the uncertainties about the benefits of treatment the CHMP was of the opinion at that point in time that the benefits of Reasanz® did not outweigh its risks and recommended that it be refused marketing authorisation.

* On June 21, 2013, Novartis has announced that the FDA has granted Breakthrough Therapy designation status to RLX030 (serelaxin), an investigational treatment for patients with acute heart failure (AHF). The FDA has concluded that RLX030 qualifies for a Breakthrough Therapy designation after considering the available clinical evidence which supports a substantial improvement over currently available therapies. The FDA\'s decision was supported by efficacy and safety results from the phase III RELAX-AHF trial, which also showed that patients who received RLX030 had a 37% reduction in mortality at 6 months after an acute heart failure episode compared to those who received conventional treatment. RLX030 is currently being assessed by health authorities around the world including the FDA and the European Medicines Agency (EMA) for the treatment of AHF.