On April 24, 2015 Eli Lilly has received its fourth U.S. Food and Drug Administration (FDA) approval for CYRAMZA (ramucirumab) (Press release, Eli Lilly, APR 24, 2015, View Source [SID:1234503179]). CYRAMZA (ramucirumab injection 10 mg/mL solution) is now also indicated in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil) chemotherapy for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

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"CYRAMZA now has approvals in advanced or metastatic forms of three of the world’s most common and deadly cancers – gastric, non-small cell lung, and colorectal – with four FDA approvals received in just over a year," said Sue Mahony, Ph.D., senior vice president and president, Lilly Oncology. "This progress is encouraging and supports our ongoing development program for CYRAMZA. Achieving today’s milestone is another example of Lilly’s commitment to people living with gastrointestinal cancers."

Dr. Mahony added, "We are also pleased with the efficient and collaborative reviews we had with the FDA on these submissions." While granted a standard review, this application for CYRAMZA in mCRC was reviewed and approved in approximately nine weeks following its submission to the FDA. All three supplemental applications for CYRAMZA received FDA approval within six months from the time of submission.

The approval is based on the Phase III trial known as RAISE, which compared CYRAMZA plus FOLFIRI to placebo plus FOLFIRI in people with mCRC who had disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Efficacy endpoints in the trial included the major efficacy outcome measure of overall survival (OS) and the supportive efficacy outcome measure of progression-free survival (PFS). The labeling for CYRAMZA contains Boxed Warnings for: hemorrhage, including severe and sometimes fatal events; gastrointestinal (GI) perforation, a potentially fatal event; and impaired wound healing. CYRAMZA should be permanently discontinued in patients who experience severe bleeding or a GI perforation. CYRAMZA should be withheld prior to surgery and discontinued if a patient develops wound healing complications. See the Important Safety Information at the end of this press release and the Prescribing Information.

For patients receiving CYRAMZA treatment, Lilly is committed to offering patient assistance programs. Patients, physicians, pharmacists, or other healthcare professionals with additional questions about CYRAMZA should contact The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or visit www.lilly.com. Healthcare professionals may also find additional product information on CYRAMZA at www.CYRAMZA.com.

About CYRAMZA (ramucirumab)
In the U.S., CYRAMZA (ramucirumab) is approved for use as a single agent or 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. It is also approved in combination with docetaxel (a type of chemotherapy) as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy. Additionally, it is approved with FOLFIRI (a type of chemotherapy) as a therapy for people with metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

CYRAMZA is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. CYRAMZA inhibited angiogenesis in an in vivo animal model.

Biogen Idec has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Biogen Idec, APR 24, 2015, View Source [SID1234503183]).

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On April 24, 2015 NEOMED reported that in collaboration with McGill University, it is embarking on a new drug discovery project that targets cancer (Press release, NEOMED, APR 24, 2015, View Source [SID1234527384]). Executed in collaboration with lead investigator Michael Witcher of the Lady Davis Institute at the Jewish General Hospital, McGill University, the project aims to identify small molecule inhibitors of poly (ADP-ribose) glycohydrolase (PARG) – an enzyme that plays a key role in DNA damage repair and in the transformation of normal cells to cancer cells, promoting their growth and invasive capability. PARG is elevated in cancers of the breast, lungs, prostate, and acute lymphoblastic leukemia. The inhibition of PARG aims to repress cancer growth and to sensitize cancer cells to DNA damage therapy.

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"Cancer is a devastating disease that is a major focus of academic and pharmaceutical research. At NEOMED, we’re looking forward to conducting an exciting project together with Dr. Witcher on this important and challenging cancer target," said Kemal Payza, Project Director at NEOMED.

"The collaboration between NEOMED and my lab has been organic from the start," stated Dr. Michael Witcher. "Innovative ideas fly around whenever the team meets, and I am confident this drug discovery program will have major clinical benefits."

On April 23, 2015 Commenting on the results, Joseph Jimenez, CEO of Novartis, reported: "Our focus on execution has resulted in a strong operational performance (Press release, Sandoz, APR 23, 2015, View Source [SID:1234506744]). We have completed the GSK and Lilly transactions and innovation continues to be strong. We had three approvals in Oncology, FDA priority review for LCZ696, Zarxio became the first biosimilar approved under the new pathway in the US and we launched Cosentyx globally. We are on track to deliver our full-year guidance."

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Continuing operations1 saw sales, core2 operating income and core EPS grow (cc2) in Q1
Net sales were USD 11.9 billion (-7%, +3% cc)2
Operating income was USD 2.8 billion (-1%, +15% cc)
Core operating income (-4%, +9% cc) grew faster than sales (cc), resulting in core margin of 30.6%
Core EPS was USD 1.33 (-1%, +11% cc))
Further strengthening of USD impacted sales by -10% and core operating income by -13%
Free cash flow2 increased 27% to USD 1.5 billion

For total Group, Q1 divestments resulted in exceptional operating income gains totaling USD 12.8 billion and net income gains of USD 10.8 billion

Strong progress on innovation continued in Q1
Three approvals in Oncology: Jakavi in polycythemia vera (EU), Farydak in multiple myeloma (US) and Jadenu for chronic iron overload (US)

LCZ696 granted FDA priority review and CHMP accelerated assessment in heart failure
Positive trials on Cosentyx in psoriasis showing superiority to Stelara, sustained two-year efficacy
Sandoz received FDA approval for first biosimilar Zarxio and in April for first substitutable generic version of Copaxone 20mg one-time-daily injection, Glatopa

Growth Products3 and Emerging Growth Markets3 continued to drive performance in Q4
Growth Products grew 14% (USD) to USD 4.7 billion, or 32% of Group net sales
Strong performance in Emerging Growth Markets (+12% cc)

Portfolio rejuvenation continued in Q1, reinforcing growth prospects for continuing operations
Growth Products3 grew 15% (USD) to USD 3.7 billion, or 31% of net sales
Strong performance in Emerging Growth Markets3 (+12% cc)

Continued progress in transforming portfolio and increasing productivity
Transactions with GSK and Lilly closed on March 2 and January 1, respectively; divestment of influenza Vaccines business to CSL expected to be completed in H2 2015
For continuing operations, core margin improved (+1.7 percentage points cc) mainly due to ongoing productivity initiatives

Outlook 2015 for continuing operations confirmed
Net sales expected to grow mid-single digit (cc); core operating income expected to grow ahead of sales at a high-single digit rate (cc) (cc)

On April 21, 2015 SignalRx Pharmaceuticals Inc., focused on developing more effective oncology drugs though molecular design imparting selected multiple target inhibition, reported the presentation of scientific data on the Company’s proprietary dual inhibitor program in oncology (Press release, SignalRx, APR 21, 2015, http://www.ireachcontent.com/news-releases/signalrx-presents-at-10th-annual-drug-discovery-chemistry-conference-on-its-dual-kinase-epigenetic-inhibitors-for-treating-cancer-500857951.html [SID1234527330]). The presentation by Dr. Donald L. Durden, MD, PhD, co-founder and science advisor to SignalRx was made at the Tenth Annual Drug Discovery Chemistry meeting at the Hilton San Diego Resort & Spa in San Diego, California.

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The oral presentation entitled "Discovery of Dual PI3K/BRD4 (kinase/epigenetic) Inhibitors" was given during the Second Annual Epigenetic Inhibitor Discovery track of the meeting at the "Advances in BET Bromodomain Inhibitor Development" session. The presentation highlighted a novel thienopyranone molecular scaffold that selectively inhibits both PI3 kinase (PI3K) and the bromodomain protein BRD4. The presentation described how molecular modeling studies were used to identify and design SignalRx’s single small molecules that can bind and inhibit simultaneously PI3K and BRD4. While the small molecule SF2523 inhibits PI3K via ATP competitive binding at the catalytic site, BRD4 inhibition appears to take place by binding in the acetyl-lysine recognition moiety of BRD4 thus blocking BRD4’s ability to alter chromatin structure and induce transcription. Blocking the binding of BRD4 to acetylated histones within chromatin can then block the transcription of various genes that are promoting cancer cell survival and growth. Recent reports suggest that BRD4 inhibition may block cancer cell resistance arising from widespread epigenetic kinome adaptation following exposure to targeted kinase inhibitor drugs which in turn may lead to more durable anticancer effects.

The presentation also included a specific rationale for the dual PI3K/BRD4 inhibition approach in cancers driven by the key cancer promoting transcription factor MYC. MYC (both cMYC and MYCN) acts downstream of many cell receptor complexes and signal transduction pathways to activate genes that drive cancer cell growth and proliferation. To date, small molecule inhibitors of MYC have been elusive. Inhibition of PI3K enhances the degradation of the cancer promoting transcription factor MYC. Inhibition of BRD4 blocks the production of MYC; thus, a dual PI3K/BRD4 inhibitor can lead to maximal MYC extinction by inhibiting these two different mechanisms. Our approach enables us to go after cancers expected to be susceptible to maximal MYC extinction as a beneficial treatment, such as CLL, medulloblastoma, multiple myeloma, and certain ovarian cancers exhibiting elevated MYCN expression. In vivo data also showed that SF2523 (50 mg/kg 3X per week) exhibited potent antitumor efficacy and anti-metastatic effects without toxicity in renal cell carcinoma xenograft models, neuroblastoma mouse models, orthotopic pancreatic cancer model and Lewis lung cancer models. Lastly, pre-clinical in vivo proof-of-concept with SF2523 was presented showing the pharmacodynamic knockdown of both the PI3K pathway and MYC in mouse neuroblastoma tumor samples four hours after administration, confirming the dual PI3K/BRD4 inhibitory profile of lead compound SF2523. Further preclinical studies of several PI3K/BRD4 dual inhibitor thienopyranones are underway to identify and select a clinical candidate.