• Results showLDE225 achieved clinically significant tumor response including disappearance of the tumor in some patients within six months of treatment
  • Basal cell carcinoma accounts for more than 80% of non-melanoma skin cancers and can be highly disfiguring and life-threatening when advanced or metastatic[1],[2],[3]
  • Data will be presented at a future scientific meeting and discussed with regulatory authorities worldwide

BASEL, Switzerland I February 19, 2014 I Novartis announced today that the pivotal trial of the investigational oral compound LDE225 (sonidegib) in advanced basal cell carcinoma met its primary endpoint of demonstrating an objective response rate among patients within six months of treatment. Objective response included complete response (clinically significant tumor response with complete absence of disease) and partial response (clinically significant tumor shrinkage)[4],[5],[6].

Basal cell carcinoma is the most common form of skin cancer, accounting for more than 80% of non-melanoma skin cancers, and can be highly disfiguring and life-threatening if it grows[1],[2],[3]. Worldwide incidence of basal cell carcinoma is rising by 10% each year due to factors such as an aging population and increased ultraviolet exposure[7]. Although basal cell carcinoma rarely metastasizes, once it does, it can be associated with significant morbidity[8].

“For people living with advanced basal cell carcinoma there are currently limited treatment options,” said Alessandro Riva, President, Novartis Oncology ad interim and Global Head, Oncology Development and Medical Affairs. “These results demonstrate the potential for LDE225 to offer a treatment option for this patient population, and we look forward to sharing these data with regulatory authorities worldwide.

Full study results will be presented at a future scientific meeting.

About the Study
The Phase II, randomized, double-blind BOLT (Basal cell carcinoma Outcomes in LDE225 Trial) study was designed to assess the safety and efficacy of two oral dose levels of  LDE225 (200 mg and 800 mg) in patients with locally advanced or metastatic basal cell carcinoma[4], which are subtypes of advanced basal cell carcinoma[9].

The primary endpoint was the proportion of patients achieving an objective response rate, defined as a confirmed complete response and partial response as their best overall response per modified RECIST criteria, within six months of starting treatment with LDE225[4]. Key secondary endpoints of the study included assessing the duration of tumor responseand the rate of complete response[4]. Other secondary endpoints included progression-free survival, time to tumor response and overall survival[4].

About LDE225
LDE225 (sonidegib) is an oral, investigational, selective smoothened inhibitor being studied in a variety of cancers[10],[11]. Smoothened (SMO) is a molecule that regulates the hedgehog (Hh) signaling pathway, which plays a critical role in stem cell maintenance and tissue repair[10],[12],[13]. LDE225 is currently in clinical development for a variety of diseases including myelofibrosis, leukemia and solid tumors[11].

Given that LDE225is an investigational compound, the safety and efficacy profile has not yet been fully established. Access to this investigational compound is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Given the  uncertainty of clinical trials, there is no guarantee that LDE225will ever be commercially available anywhere in the world.

The foregoing release contains forward-looking statements that can be identified by words such as “investigational,” “can,” “will,” “future,” “rising,” “potential,” “look forward,” “being studied,” or similar terms, or by express or implied discussions regarding potential marketing approvals for LDE225, or regarding potential future revenues from LDE225. 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 LDE225 will be submitted or approved for any indication in any market, or at any particular time. Nor can there be any guarantee that LDE225 will be commercially successful in the future. In particular, management’s expectations regarding LDE225 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 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.

About Novartis
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, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 136,000 full-time-equivalent associates and operate in more than 140 countries around the world.

For more information, please visit http://www.novartis.com.

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[1] Skin Cancer Foundation. “Basal Cell Carcinoma.”Available at: http://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma.  Accessed on February 14, 2014.
[2] Skin Cancer Foundation. “Skin Cancer Facts.” Available at: http://www.skincancer.org/skin-cancer-information/skin-cancer-facts. Accessed on February 14, 2014.
[3] Rubin AI, Chen EH, Ratner D (2005). Current Concepts: Basal-Cell Carcinoma. N Engl J Med; 353:2262-9.
[4] ClinicalTrials.gov. “
A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma (BOLT)” Available at: http://clinicaltrials.gov/ct2/show/NCT01327053?term=%22LDE225%22+and+%22BOLT%22&rank=1. Accessed on February 14, 2014.
[5] National Cancer Institute Dictionary of Cancer Terms. “Complete Response.” Available at: http://www.cancer.gov/dictionary?CdrID=45652. Accessed on February 14, 2014.
[6] National Cancer Institute Dictionary of Cancer Terms. “Partial Response.” Available at: http://www.cancer.gov/dictionary?CdrID=45819. Accessed on February 14, 2014.
[7] Wong C S M, Strange R C, Lear J T (2003). Basal cell carcinoma. BMJ; 327:794-798.
[8] Copcu E, Aktas A. Simultaneous two organ metastases of the giant basal cell carcinoma of the skin. Int Semin Surg Oncol. 2005;2:1-6. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC544837/. Accessed on February 14, 2014.
[9] Skin Cancer Foundation. “Basal Cell Carcinoma Treatment Options.” Available at http://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma/bcc-treatment-options. Accessed on February 14, 2014.
[10] Stuetz A, et al. LDE225, a specific smoothened inhibitor, for the topical treatment of nevoid basal cell
carcinoma syndrome (Gorlin’s syndrome). Melanoma Research. 2010; 20:e40. Available at: http://journals.lww.com/melanomaresearch/Fulltext/2010/06001/FC24_LDE225,_a_specific_smoothened_inhibitor,_for.87.aspx#FC24_LDE225%2C_a_specific_smoothened_inhibitor%2C_for.87.aspx?s=2&_suid=139234380607909969110518506816.
[11] Novartis.com. “The Pipeline of Novartis Oncology: LDE225.” Available at: http://www.novartisoncology.com/research-innovation/pipeline.jsp#. Accessed on February 14, 2014.
[12] Children’s Medical Research Center, Children’s Memorial Hospital/Northwestern University Feinberg School of Medicine. “The Sonic hedgehog/patched/gli signal transduction pathway.” Available at http://www.childrensmrc.org/iannaccone/gli/. Accessed on February 14, 2014.
[13] Gupta S, Takebe N, LoRusso P.
Targeting the Hedgehog pathway in cancer. Ther Adv Med Oncol. 2010 July; 2(4): 237-250. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126020/. Accessed on February 14, 2014.

SOURCE: Novartis