On December 14, 2012, the U.S. Food and Drug Administration (FDA) approved Iclusig (ponatinib) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases. Iclusig is Ariad's first approved product.
On May 7, 2013, Ariad reported Iclusig revenues for the first time.
Net sales of the drug were $6.4 million for the quarter ended March 31, 2013. As of March 31, 2013, Ariad had deferred revenue of $3.3 million in the United States, representing Iclusig inventory at specialty pharmacies and distributors, which had not yet shipped to the end customer by the end of the quarter.
As of March 31, 2013, more than 325 patients in the United States were being treated with Iclusig obtained commercially based on physicians' prescriptions. At the end of April 2013, there were approximately 300 unique physician prescribers of Iclusig and over 250 unique accounts were using the drug. The company recently reported that approximately 70% of the Iclusig prescribers are community-based physicians. This greater than two to one distribution in favor of community physicians over academic physicians indicates that Iclusig is being prescribed broadly among hematologists, oncologists in diverse clinical settings, not just investigators who participated in the company's clinical trials.
European Union (EU) regulators are expected to rule by mid-2013 on Ariad's application to sell the drug in Europe. Ariad is confident that Iclusig will be approved in the European Union in the second quarter of 2013. The company expects to launch Iclusig in the EU during July 2013.
Ariad expects that Iclusig will be indicated for use in CML and Ph+ALL in the second-line setting and later lines in patients who are resistant to Bristol-Myer Squibb's (NYSE:BMY) Sprycel (dasatinib) or Novartis' (NYSE:NVS) Tasigna (nilotinib), or who have the T315I mutation of BCR-ABL. Ariad expects to be launch-ready in Europe by July 1, 2013.
The company has already established a base in Lausanne, Switzerland to facilitate Iclusig sales in the EU. In Europe, Ariad has made major strides in executing on its commercial plan with the initiation of early-access programs and the implementation of pricing and reimbursement activities. The company has established its European supply chain, and hired key personnel for its European leadership team. Ariad plans to be commercial-ready in Europe on July 1, 2013.
Based on the results of the ongoing Phase I/II trial of Iclusig in resistant and intolerant CML in Philadelphia-positive ALL in Japan, Ariad expects to file for regulatory approval in Japan in mid-2014. The company expects to submit regulatory filings in Canada and Australia in the third quarter of 2013.
The global, Phase III EPIC trial which compares Iclusig to Novartis' blockbuster drug Gleevec (imatinib) in patients with newly diagnosed CML, is advancing. The company expects to reach full patient enrollment in the fourth quarter of 2013. Approximately 120 clinical sites in 20 countries are now participating in the trial, and data from an interim analysis of safety and efficacy are anticipated in the third quarter of 2014.
Iclusig is frequently referred to as a "first in class" drug. While the FDA has only approved Iclusig for leukemia patients who are resistant or intolerant to other drugs, research is ongoing which may enable Iclusig to expand the label for other indications, which would provide Ariad with an opportunity to gain a larger portion of the estimated $4.5 billion annual CML market now dominated by Novartis with their Gleevec and Tasigna products and Bristol-Myers Squibb with their Sprycel drug.
The optimal first-line treatment for patients with newly diagnosed chronic-phase CML is controversial. When used as first-line treatments, some studies have found that Tasigna, Sprycel and Bosulif have all produced better response rates than Gleevec.
In July 2012, Ariad launched a Phase III trial testing Iclusig head to head with Gleevec in people newly diagnosed with CML. Positive results from that trial could propel Iclusig to blockbuster drug status. Harvey Berger, Ariad's CEO, has predicted that Iclusig could generate $1.5 billion in projected revenue if the company can broaden the label to include its use as an initial treatment for leukemia.
Ariad is currently working to increase Iclusig sales in the United States while waiting for approval of the drug in the European Union this quarter. The company has taken the steps necessary to implement an effective product launch for Inclusig in the EU.
Ariad also plans to begin a Phase II trial testing Iclusig in gastrointestinal stromal tumor (GIST) patients.
The Phase I portion of the company's Phase I/II clinical trial of AP26113 is nearing completion. AP26113 is a small molecule that in preclinical studies has exhibited activity as a potent tyrosine-kinase inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) and c-ros oncogene 1 (ROS1). Like Iclusig, AP26113 was internally discovered by Ariad scientists, and targets unique genetic features of cancer cells.
ALK was first identified as a chromosomal rearrangement in anaplastic large-cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as ALCL. Since ALK is generally not expressed in normal adult tissues, it represents a promising molecular target for cancer therapy.
Ariad expects to transition into the Phase II expansion cohorts by the American Society of Clinical Oncology annual meeting in June. In parallel to enrollment in the Phase II expansion cohorts, the company plans to begin a pivotal trial of AP26113 in ALK-positive NSCLC patients who are resistant to Pfizer's (NYSE:PFE) Xalkori (crizotinib) in the third quarter of 2013. Ariad is expected to provide clinical updates on AP26113 at the 2013 ASCO annual meeting and at the European Society of Medical Oncology (ESMO) annual meeting.
Exelixis, Inc. (NASDAQ:EXEL)
South San Francisco, California-based Exelixis, Inc. has generated a great deal of excitement with cabozantinib, a small molecule inhibitor of the tyrosine kinases, c-Met and VEGFR2, that has shown to reduce tumor growth, metastasis, and angiogenesis.
AMTC is a rare disease that is difficult to treat. The National Cancer Institute estimates that there are approximately 2,250 people in the United States with AMTC, About 500 to 700 people reach the advanced stage of MTC every year.
On January 24, 2013, Exelixis announced the commercial availability of Cometriq (cabozantinib) for the treatment of patients with progressive, metastatic MTC.
On May 3, 2012, Exelixis announced a broad expansion of the cabozantinib clinical development program under a Cooperative Research and Development Agreement with the National Cancer Institute's Cancer Therapy Evaluation Program, with the approval of the initial program of 13 proposed clinical trials under the agreement.
The CRADA provides for funding for as many as 20 active clinical trials each year for a five-year period, which Exelixis believes will enable a broad expansion of the cabozantinib development program in a cost-efficient manner. When initiated, these trials will substantially increase the number of indications and disease settings in which cabozantinib is being investigated, and will aid in prioritizing the next set of pivotal trials. Exelixis also has an Investigator-Sponsored Trial program that is generating additional data on cabozantinib in a variety of treatment settings.
On May 30, 2012, Exelixis announced the initiation of COMET-1, a Phase III pivotal trial testing the effectiveness of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC). The primary endpoint for COMET-1 is overall survival (OS) in mCRPC patients who have had disease progression after treatment with docetaxel and abiraterone acetate (Zytiga) and/or MDV3100, also known as Xtandi or enzalutamide. COMET-1 is being conducted because there is an unmet need for therapies that demonstrate survival benefits for patients that have received both chemotherapy and either MDV3100 or abiraterone. Exelixis expects data from COMET-1 to be available in the first half of 2014.
There is reason for investors and prostate cancer patients to have high hopes for cabozantinib.
On December 4, 2012, University of Michigan Comprehensive Cancer Center announced results that found Cometriq demonstrated rapid effects on prostate cancer that had metastasized to bone. About two-thirds of patients treated with the drug showed improvements on their bone scans, with 12% achieving complete resolution of uptake on the scans.
Cabozantinib is also being studied as a potential treatment for ovarian cancer, melanoma, breast cancer, non-small cell lung cancer, hepatocellular cancer and kidney cancer.
The company's early-stage discovery and research expertise has generated multiple compounds and programs that target key pathways in cancer and metabolic diseases. Exelixis has established collaborations with Bristol-Myers Squibb, Genentech, Inc. (a wholly-owned member of the Roche Group (OTCQX:RHHBY), GlaxoSmithKline (NYSE:GSK), Sanofi (SNY), Merck (MRK) and Daiichi-Sankyo Company Limited (OTCPK:DSNKY), for a variety of compounds and programs.
By out-licensing these compounds or programs to a partner for further development and commercialization, the company usually has no further unfunded cost obligations related to such compounds or programs and may be entitled to receive research funding, milestones and royalties or a share of profits from commercialization.
Cabozantinib is currently being studied in over 30 clinical trials. In Exelixis-sponsored trials, cabozantinib has shown signs of tumor shrinkage in 12 of 13 tumor types studied, including medullary thyroid, prostate, breast, ovarian, and non-small cell lung cancer, melanoma, and hepatocellular carcinoma.
Merrimack Pharmaceuticals (MACK)
Founded by six professors from Harvard University and the Massachusetts Institute of Technology, Merrimack Pharmaceuticals candidates in preclinical development and an active Systems Biology-driven discovery effort.
MM-398 is Merrimack's lead drug currently in Phase 3 trials to determine if the drug is effective in the treatment of patients with metastatic pancreatic cancer who fail treatment with the chemotherapeutic drug, gemcitabine. There are no approved therapies for patients with metastatic pancreatic cancer who fail treatment with gemcitabine, which is marketed by Eli Lilly (NYSE:LLY) as Gemzar. Gemzar is the standard of care drug for pancreatic cancer.
MM-398 is a novel, stable nanoliposomal encapsulation of the conventional chemotherapy irinotecan. MM-398 is designed to optimize the delivery of irinotecan by extending the duration of circulation in the body and preferentially activating the drug within the tumor to achieve higher levels of the active drug. MM-398 is a new version of irenotecan, a chemotherapeutic drug marketed as Camptosar by Pfizer. Irenotectan is used for the treatment of colon and rectal cancers. MM-398 encases irenotectan in a liposome to allow for longer circulation time, greater efficacy and fewer side effects.
In January 2012, Merrimack initiated a pivotal Phase III clinical trial of MM-398 for the treatment of patients with metastatic pancreatic cancer who have previously failed treatment with gemcitabine.
Merrimack believes that MM-398 has potential uses in a number of other indications, including colorectal cancer, lung cancer, gastric cancer and glioma. In addition to NAPOLI-1, there are ongoing Phase I and Phase II clinical trials of MM-398 in glioma and colorectal cancer. MM-398 has been tested in several clinical trials including a Phase II single agent study of MM-398 in metastatic pancreatic cancer and an ongoing Phase II study of MM-398 in combination with 5-FU and leucovorin in patients with metastatic colorectal cancer.
The company is also developing MM-121, a fully human monoclonal antibody that targets ErbB3, a cell surface receptor, or protein attached to the cell membrane that mediates communication inside and outside the cell, that has been identified as a potentially important target in a range of cancers.
On May 23, 2013, Merrimack announced that the company completed enrollment in a Phase II trial of MM-121 in combination with Pfizer's Aromasin (exemestane) in postmenstrual women with locally advanced or metastatic estrogen receptor positive and/or progesterine receptor positive receptor positive ((PR+)) HER2-negative breast cancer.
In partnership with Sanofi , MM-121 is also being evaluated in Phase II studies in advanced ovarian cancer, hormone sensitive breast cancer, non-small cell lung cancer (NSCLC) and HER2 negative neoadjuvant breast cancer.
Merrimack has a robust pipeline based on the company's sophisticated Network Biology-based drug development technology. While most investors and analysts are focused on the near-term progress of MM-398 and the NAPOLI-1 trial, Merrimack's other candidates, particularly MM-121, which is partnered with Sanofi, also show promise for the treatment of ovarian, breast, and lung cancers.