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Lilly’s CYRAMZA® (ramucirumab) in Combination with Paclitaxel Granted FDA Approval for Advanced Gastric Cancer After Prior Chemotherapy

On November 5, 2014 Eli Lilly and Company reported that the U.S. Food and Drug Administration (FDA) has approved CYRAMZA (ramucirumab) in combination with paclitaxel (a type of chemotherapy) as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy (Press release, Eli Lilly, NOV 5, 2014, View Source [SID:1234500920]). CYRAMZA now has two FDA approvals for these patients. Today’s announcement follows the April approval of CYRAMZA as a single agent – the first approval of a treatment in the U.S. for patients in this setting.

“This FDA approval of CYRAMZA represents another milestone for people battling this devastating and difficult-to-treat disease,” said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. “Lilly is pleased to continue delivering on its commitment to provide new treatment options to people living with cancer and those who care for them.”

Stomach cancer is the fifth most common cancer in the world and is the third-leading cause of cancer death.i In the U.S., approximately 22,000 people will be diagnosed with stomach cancer in 2014.ii CYRAMZA (ramucirumab injection 10 mg/mL solution) is the only FDA-approved second-line treatment option for patients with advanced or metastatic gastric or GEJ adenocarcinoma whose disease has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

This FDA approval for CYRAMZA is based on the Phase III RAINBOW trial, which compared CYRAMZA plus paclitaxel to placebo plus paclitaxel. Efficacy endpoints in the trial included the major efficacy outcome measure of overall survival and the supportive efficacy outcome measures of progression-free survival and objective response rate. The labeling for CYRAMZA contains a Boxed Warning regarding increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. CYRAMZA should be permanently discontinued in patients who experience severe bleeding. See the Important Safety Information at the end of this press release and the Prescribing Information.

CYRAMZA has been granted Orphan Drug Designation by the FDA for this indication. Orphan drug status is given in the U.S. by the FDA’s Office of Orphan Products Development (OOPD) to medicines that show promise for the treatment of rare diseases.

Corcept Therapeutics Announces Third Quarter 2014 Financial Results and Provides Corporate Update

On November 4, 2014 Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic, oncologic and psychiatric disorders reported its financial results for the quarter ended September 30, 2014 (Press release, Corcept Therapeutics, NOV 4, 2014, http://www.corcept.com/news_events/view/pr_1415137296 [SID:1234511994]). The company also provided an update on its clinical programs and revised its 2014 revenue guidance.

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Third Quarter Financial Results and 2014 Revenue Guidance

Corcept recognized $7.3 million in net revenue for the third quarter of 2014 compared to $5.9 million in the second quarter, an increase of 24 percent. The company’s net loss in the third quarter on a GAAP basis was $6.0 million, or $0.06 per share, compared to a net loss of $7.6 million, or $0.07 per share, in the second quarter.
The company’s net loss on a GAAP basis included significant non-cash items of $2.1 million in the third quarter and $2.2 million in the second quarter. Excluding these items, the company’s net loss on a non-GAAP basis was $3.9 million, or $0.04 per share, for the third quarter of 2014 and $5.4 million or $0.05 per share, for the second quarter.
As of September 30, 2014, the company held cash and cash equivalents of $26.8 million.
The company revised the range of its 2014 revenue guidance to $25-27 million.
"Our Cushing’s syndrome commercial business continues to grow and now generates cash to fund an increasing portion of our research and development activities," said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer. "While there is a group of endocrinologists who have seen Korlym’s benefits and have become repeat prescribers, there are many physicians who have not yet written their first prescription. These physicians represent the potential for better treatment for more patients and significant future revenues."

Clinical Pipeline Progress

"We expect to have identified tolerable doses of Korlym and Halaven (eribulin) in our triple-negative breast cancer study by year-end, when the study’s efficacy phase is scheduled to begin. In September, we began dosing patients in our Phase 1 trial of CORT 125134. We will advance additional selective 1 glucocorticoid receptor (GR) antagonists into the clinic next year. GR antagonism is an exciting area of research that will generate interesting data in 2015, both from our own studies and from those being undertaken by our academic collaborators."

Financial Results

For the third quarter of 2014, Corcept recognized net product revenue of $7.3 million. The company reported a net loss of $6.0 million, or $0.06 per share, for the third quarter of 2014 compared to a net loss of $10.9 million, or $0.11 per share, for the same period in 2013.

The net loss on a GAAP basis for the third quarter of 2014 and for the third quarter of 2013 included non-cash stock-based compensation expenses of $1.2 million and $1.3 million, respectively. The company also recognized non-cash interest expense related to its capped royalty financing transaction of $895,000 in the third quarter of 2014 and $1.1 million in the same period in 2013.

After adjusting for these items, the company’s net loss on a non-GAAP basis was $3.9 million, or $0.04 per share, for the third quarter of 2014, compared to $8.5 million, or $0.08 per share, for the third quarter of 2013. A reconciliation of GAAP net loss to non-GAAP net loss is included below.

Operating expenses were $12.4 million for the third quarter of 2014 and also for the corresponding period in 2013.

Selling, general and administrative expenses in the third quarter were $9.1 million compared to $7.2 million for the comparable period in 2013.
Research and development expenses in the third quarter of 2014 were $3.0 million, compared to $5.2 million for the third quarter of 2013.
Corcept’s cash balance as of September 30, 2014 was $26.8 million, compared to $54.9 million at December 31, 2013. Net cash used in the company’s operating activities for the third quarter of 2014 was $5.9 million as compared to $9.0 million for the second quarter of 2014 and $11.1 million for the first quarter of 2014.

About Korlym

Korlym competitively blocks the glucocorticoid receptor type II (GR), one of the two receptors to which cortisol normally binds, thereby inhibiting the effects of excess cortisol in patients with Cushing’s syndrome. In April 2012, Corcept made Korlym available as a once-daily oral treatment of hyperglycemia secondary to endogenous Cushing’s syndrome in adult patients with glucose intolerance or diabetes mellitus type 2 who have failed surgery or are not candidates for surgery. Korlym was the first FDA-approved treatment for that illness and the FDA has designated it as an Orphan Drug for that indication.

About Cushing’s Syndrome

Endogenous Cushing’s syndrome is caused by prolonged exposure of the body’s tissues to high levels of the hormone cortisol and is generated by tumors that produce cortisol or ACTH. Cushing’s syndrome is an orphan indication that most commonly affects adults aged 20-50. An estimated 10-15 of every one million people are newly diagnosed with this syndrome each year, resulting in over 3,000 new patients annually in the United States. An estimated 20,000 patients in the United States have Cushing’s syndrome. Symptoms vary, but most people have one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing’s syndrome can affect every organ system in the body and can be lethal if not treated effectively.

About Triple-Negative Breast Cancer

Triple-negative breast cancer is a form of the disease in which the three receptors that fuel most breast cancer growth – estrogen, progesterone and the HER-2/neu gene – are not present. Because the tumor cells lack the necessary receptors, treatments that target estrogen, progesterone and HER-2 receptors are ineffective. In 2013, approximately 40,000 women were diagnosed with triple-negative breast cancer. There is no FDA-approved treatment and neither a targeted treatment nor an approved standard chemotherapy regimen for relapsed triple-negative breast cancer patients exists.

About CORT 125134

CORT 125134 is a potent, competitive antagonist at the GR-II receptor, but does not have affinity for the progesterone, estrogen, AR androgen or GR-I (mineralocorticoid) receptors. The company has begun a Phase 1 study of the safety and tolerability of CORT 125134, one of its next-generation selective GR-II antagonists.

AstraZeneca and Pharmacyclics enter clinical trial collaborations in oncology

On November 4, 2014 AstraZeneca and Pharmacyclics reported that they have entered into clinical trial collaborations to evaluate novel combination therapies targeting solid tumours and a number of haematological cancers (Press release AstraZeneca, NOV 4, 2014, View Source;astrazeneca-and-pharmacyclics-enter-clinical-trial-collaborations-oncology [SID:1234500963]).

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The first collaboration, focusing on solid tumours, will evaluate the efficacy and safety of IMBRUVICA (ibrutinib), Pharmacyclics’ oral Bruton’s tyrosine kinase inhibitor in combination with AstraZeneca’s anti-PD-L1 antibody, MEDI4736.

The second collaboration will focus on haematological cancers and will explore separate combinations of two different AstraZeneca investigational PI3 kinase pathway inhibitors with IMBRUVICA, for the treatment of patients with relapsed or refractory diffuse large B-cell lymphomas. Preclinical evidence suggests that the combination of IMBRUVICA with these investigational medicines may enhance their effects.

Under the terms of the agreements, AstraZeneca and Pharmacyclics will collaborate on a non-exclusive basis and multiple Phase I and Phase IIa studies may be considered and conducted. The studies focused on solid tumours will be led by Pharmacyclics, while AstraZeneca will lead those exploring haematological cancers. The Phase I element of each study is expected to establish a recommended safe and tolerable dose and schedule for the combination and the Phase IIa element will assess its safety and efficacy in an expanded patient population. The financial terms of the agreement have not been disclosed. The results of the clinical studies will be used to determine whether further clinical development of the different combinations is warranted.

Susan Galbraith, Head of AstraZeneca’s Oncology Innovative Medicines Unit said: "There is a clear and significant unmet need in the treatment of haematological malignancies, an area of increasing focus for AstraZeneca. Our partnership with Pharmacyclics will allow us to explore new and potentially potent treatment combinations, which could have a positive impact on patient outcomes."

"We are optimistic that combining our oral once-per-day IMBRUVICA with other agents has the potential to enhance efficacy and duration across the landscape of haematological cancers," said Bob Duggan, Chairman & CEO, Pharmacyclics. "In addition, we are extremely interested in the potential for IMBRUVICA in combination with an anti-PD-L1 antibody to improve the treatment of solid tumours in patients who need better therapeutic options."

Exelixis Announces Positive Top-Line Results From a Phase 2 Trial of Cabozantinib and Erlotinib in Patients With EGFR Wild-Type Non-Small Cell Lung Cancer

On November 4, 2014 Exelixis reported positive top-line results from a randomized phase 2 trial of cabozantinib and erlotinib alone or in combination as second- or third-line therapy in patients with stage IV EGFR wild-type non-small cell lung cancer (NSCLC) (Press release Exelixis, NOV 4, 2014, View Source [SID:1234500919]). This trial (Study E1512) is sponsored by the U.S. National Cancer Institute (NCI) through a Cooperative Research and Development Agreement between the Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, NCI and Exelixis. Study E1512 was designed and is being conducted by the ECOG-ACRIN Cancer Research Group as part of Exelixis’ collaboration with the NCI. Joel Neal, M.D., Ph.D., from ECOG-ACRIN member institution Stanford University/Stanford Cancer Institute, chairs the study.

In the E1512 trial, 125 patients were randomized to one of the three arms: erlotinib, cabozantinib, or the combination. During a pre-planned interim ECOG-ACRIN Data Safety Monitoring Committee analysis for futility, it was found that the trial met its primary endpoint of improving progression-free survival (PFS) with cabozantinib alone and also with the combination of cabozantinib plus erlotinib, as compared to erlotinib alone, and the results were highly statistically significant. Safety data were consistent with those observed in other trials of cabozantinib. At time of analysis, the median follow-up was 5.9 months and overall survival data were immature.

The results of the trial are the subject of ongoing analyses and will be submitted by the investigators for presentation at a future medical conference.

Exelixis President and CEO, Michael M. Morrissey, Ph.D., commented on the results: “This is one of the first substantial data sets from our collaboration with NCI-CTEP, which has enabled us to broaden the cabozantinib development program while focusing our internal resources on our pivotal trials. We are excited by these positive results and are looking forward to working with the trial investigators to support future development of cabozantinib in NSCLC and beyond, while we await top-line results from our pivotal phase 3 trial METEOR in metastatic renal cell carcinoma, now anticipated in the second quarter of 2015.”

Amgen Announces Top-Line Secondary Endpoint Results Of Phase 3 Trebananib TRINOVA-1 Trial In Patients With Recurrent Ovarian Cancer

On November 4, 2014 Amgen reported the top-line secondary endpoint results of overall survival from the Phase 3 TRINOVA-1 trial in women with recurrent platinum-resistant ovarian cancer (Press release, Amgen, NOV 4, 2014, View Source [SID:1234500917]). The study, which evaluated trebananib plus paclitaxel versus placebo plus paclitaxel, did not demonstrate a statistically significant improvement in overall survival. Median overall survival was 19.3 months in the trebananib arm versus 18.3 months in the control arm. The data will be submitted to a future medical conference and for publication.

In the previously reported primary endpoint analysis, the data demonstrated a statistically significant difference in progression-free survival for trebananib. In that analysis, patients treated with trebananib showed a 34 percent reduction in the risk of disease progression or death (HR = 0.66, 95 percent CI, 0.57, 0.77, p<0.001). The median progression-free survival was 7.2 months in the trebananib arm versus 5.4 months in the control arm. "While the overall survival results of the TRINOVA-1 study are disappointing, this study is the first of three Phase 3 trials designed to evaluate the safety and efficacy of trebananib in patients with ovarian cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We continue to explore the potential of trebananib's novel anti-tumor mechanism of action in other cancer settings." In the trebananib arm, the most frequently reported adverse events were localized edema, nausea and alopecia. The rate of discontinuation of investigational product due to adverse events was 20 percent in the trebananib arm versus seven percent in the control arm. No new safety signals were detected. Data from another trial in the recurrent platinum-resistant population (TRINOVA-2) is expected in Q4 2014. Data from a trial evaluating trebananib in combination with first-line chemotherapy treatment for patients with ovarian cancer (TRINOVA-3) is expected in 2015. TRINOVA-1 Trial Design (NCT01204749) TRINOVA-1 (A Study of AMG 386 or Placebo, in Combination With Weekly Paclitaxel Chemotherapy, as Treatment for Ovarian Cancer, Primary Peritoneal Cancer and Fallopian Tube Cancer) is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study evaluating trebananib in over 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15 mg/kg of intravenous trebananib weekly plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off). Other ongoing Phase 3 studies of trebananib include TRINOVA-2 and TRINOVA-3. TRINOVA-2 is evaluating whether trebananib plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival in recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. TRINOVA-3 is evaluating trebananib or placebo in combination with paclitaxel and carboplatin in the first-line treatment of epithelial ovarian, primary peritoneal or fallopian tube cancer.