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Spectrum Pharmaceuticals Receives Complete Response Letter (CRL) from U.S. Food and Drug Administration (FDA) for EVOMELA™ (melphalan) for Injection

On October 23, 2015 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported that it has received a Complete Response Letter from the U.S. Food and Drug Administration (FDA) (Press release, Spectrum Pharmaceuticals, OCT 23, 2015, View Source [SID:1234507771]). A Complete Response Letter is a communication from the FDA that informs companies that an application cannot be approved in its present form. In the letter, the FDA did not identify any clinical deficiency in Spectrum’s NDA package.

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"We will work swiftly with the FDA to address the Complete Response Letter," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "We remain committed to bringing EVOMELA to the market for patients and plan to work closely with the FDA."

Spectrum Pharmaceuticals gained global development and commercialization rights to EVOMELA from Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) in March 2013. Spectrum assumed responsibility for completing the pivotal Phase 2 clinical trial, and was responsible for filing the NDA. Under the license agreement, Ligand received a license fee and is eligible to receive milestone payments, as well as royalties following potential commercialization.

On October 22, 2015, Roche Holding AG ("Roche") disclosed that its GATSBY trial assessing its product, Kadcyla (ado-trastuzumab emtansine), for second-line treatment of HER2-positive advanced gastric cancer did not meet its primary endpoint (Filing, 8-K, ImmunoGen, MAY 22, 2015, View Source [SID:1234512502]). Roche expects the detailed clinical findings from GATSBY to be reported at a future medical conference. Earlier this year, ImmunoGen, Inc. entered into a royalty purchase agreement that monetized the Company’s royalties on Kadcyla sales.

Moderna Launches Caperna LLC, Its Fourth Venture, to Develop Personalized Cancer Vaccines

On October 22, 2015 Moderna Therapeutics, a pioneer in the development of messenger RNA (mRNA) Therapeutics, reported the launch of Caperna LLC, the fourth Moderna venture, which will focus exclusively on the advancement of personalized cancer vaccines.

Caperna will apply Moderna’s mRNA vaccine technology to the field of cancer vaccines, building on advances in recent years in cancer immunotherapy, including the availability of checkpoint inhibitors and the ability to rapidly determine individual patient mutations. Caperna will develop personalized cancer vaccines that encode a patient’s specific neoepitopes, utilizing Moderna’s unique infrastructure to manufacture within weeks small batches of vaccines tailored to each patient.

Substantial efforts at Moderna’s infectious disease venture Valera have demonstrated preclinical efficacy of Moderna’s mRNA-based vaccines in multiple viral disease models, which has led to the nomination of several viral vaccine development candidates. These advancements have spurred the formation of Caperna and the pursuit of vaccine development for the treatment of cancer.

Tal Zaks, M.D., Ph.D., Chief Medical Officer of Moderna, who was formerly Senior Vice President and Head of Global Oncology at Sanofi, will serve as Interim President of Caperna. Nicholas Valiante, Ph.D., who recently joined Moderna from Novartis Vaccines where he was Global Head of Immunology & Immunotherapy Research, will serve as Vice President and Head of Personalized Vaccine Sciences.

"With such a potent vaccine platform and a manufacturing process that lends itself directly to rapid production of patient-specific therapies, we believe Moderna’s mRNA approach will offer distinct advantages in the development of new cancer therapies," said Dr. Zaks. "We expect our ability to specifically activate and direct the immune system will synergize with checkpoint inhibitor therapies like PD-1 antibodies."

"What is perhaps most exciting about our approach and our core protein expression platform is its potential to leverage a broad spectrum of leading-edge drug modalities," said Stéphane Bancel, Chief Executive Officer of Moderna. "Caperna is an important example of Moderna’s unique ability to rapidly translate our ever-evolving understanding of mRNA into new therapeutic opportunities that have the potential to impact and change numerous lives. Caperna will be backed by Moderna’s $840 million of cash on hand."

Onkaido, Moderna’s initial oncology venture, remains focused on the development of mRNA-based therapeutics for oncology in areas outside of the personalized cancer vaccine effort at Caperna.

FDA approves new treatment for advanced pancreatic cancer

On October 22, 2015 The U.S. Food and Drug Administration reported it approved Onivyde (irinotecan liposome injection), in combination with fluorouracil and leucovorin, to treat patients with advanced (metastatic) pancreatic cancer who have been previously treated with gemcitabine-based chemotherapy (Press release, , OCT 22, 2015, View Source [SID:1234507767]).
According to the National Cancer Institute, there will be 48,960 new cases of pancreatic cancer diagnosed in the U.S. in 2015, and nearly the same number of deaths caused by the disease (40,560). Pancreatic cancer can be difficult to diagnose early and treatment options are limited, especially when the disease has spread to other parts of the body (metastatic disease) and surgery to remove the tumor is not possible.

"Many FDA staff who review drug applications are clinicians as well, so it’s especially rewarding when we are able to expedite access to new treatments for patients with unmet needs," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. "By using the Priority Review designation for the application for Onivyde, patients will have earlier access to a drug that helps extend survival."

The FDA granted Priority Review and orphan drug designations for Onivyde. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as tax credits, user fee waivers, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

The effectiveness of Onivyde was demonstrated in a three-arm, randomized, open label study of 417 patients with metastatic pancreatic adenocarcinoma whose cancer had grown after receiving the chemotherapeutic drug gemcitabine or a gemcitabine-based therapy. The study was designed to determine whether patients receiving Onivyde plus fluorouracil/leucovorin or Onivyde alone lived longer than those receiving fluorouracil/leucovorin. Patients treated with Onivyde plus fluorouracil/leucovorin lived an average of 6.1 months, compared to 4.2 months for those treated with only fluorouracil/leucovorin. There was no survival improvement for those who received only Onivyde compared to those who received fluorouracil/leucovorin.

In addition, patients receiving Onivyde plus fluorouracil/leucovorin had a delay in the amount of time to tumor growth compared to those who received fluorouracil/leucovorin. The average time for those receiving Onivyde plus fluorouracil/leucovorin was 3.1 months compared to 1.5 months for those receiving fluorouracil/leucovorin.

The safety of Onivyde was evaluated in 398 patients who received either Onivyde with fluorouracil/leucovorin, Onivyde alone or fluorouracil/leucovorin. The most common side effects of treatment with Onivyde included diarrhea, fatigue, vomiting, nausea, decreased appetite, inflammation in the mouth (stomatitis) and fever (pyrexia). Onivyde was also found to result in low counts of infection-fighting cells (lymphopenia and neutropenia). Death due to sepsis following neutropenia has been reported in patients treated with Onivyde.

The labeling for Onivyde includes a boxed warning to alert health care professionals about the risks of severe neutropenia and diarrhea. Onivyde is not approved for use as a single agent for the treatment of patients with metastatic pancreatic cancer.

Onivyde is marketed by Merrimack Pharmaceuticals Inc. of Cambridge, Massachusetts.

Knowledge-Based Software Can Significantly Expedite Creation of High-Quality Radiotherapy Treatment Plans for Precise Tumor Targeting

On October 22, 2015 Varian Medical Systems reported that studies presented earlier this week at the 2015 annual meeting of the American Society for Radiation Oncology (ASTRO) confirmed that knowledge-based treatment planning software can dramatically improve the speed and quality of cancer care (Press release, Varian Medical Systems, OCT 22, 2015, View Source [SID:1234507766]). One award-winning study by a team using RapidPlan software from Varian Medical Systems (NYSE: VAR) showed that radiotherapy treatment planning for cervical cancer can be done in minutes rather than hours, with superior quality.

In a presentation that was named among the "Best of ASTRO" and won the Basic/ Translational Science Abstract Award in the physics category, Nan Li, PhD, postdoctoral fellow at the University of California, San Diego (UCSD), and her team1 reported on their use of a RapidPlan model that was based on a refined sample of 86 previously-treated cervical cancer cases. They found that treatment planning time for intensity-modulated radiation therapy took an average of 6.85 minutes.[1] According to Kevin Moore, PhD, senior author on the study, UCSD dosimetrists estimate that manual GYN planning would require anywhere from 2-6 hours of optimization. "The use of knowledge-based planning represents a considerable time savings and reduced personnel costs," he said.

RapidPlan also improved plan quality compared to conventionally generated plans by minimizing the impact on normal surrounding tissues. "With both dramatic efficiency gains and improved normal tissue sparing, the final automated planning module was validated as both a clinical trial quality control system and a valuable tool for high-quality clinical planning in cervical cancer," observed Li.

Moore and his physician colleagues from UCSD also described work where stereotactic radiosurgery (SRS) treatment plans created using automated knowledge-based planning algorithms that they developed were set against manually-created clinical plans in a blinded comparison study.[2]

"In a clear majority of the cases, automated SRS planning demonstrated superior or equivalent plan quality to existing manual planning processes," Moore said. "Further refinement of algorithms to balance the complex clinical tradeoffs for high-priority organs-at-risk . . . will likely improve this technique further."

Researchers from Duke University evaluated a "rapid learning approach" in which clinicians "train" the RapidPlan tool by establishing a base knowledge model and continuously evaluate and update this knowledge model using subsequent cases. In their research on pelvic cancer cases, Jackie Wu, PhD, professor of radiation oncology, and her colleagues compared the RapidPlan rapid learning approach to the batch training method: knowledge modeling based on a static set of training cases.[3]

"The rapid learning approach is able to learn knowledge models for multiple cancer types in the pelvic region with comparable accuracy to the batch training method and with improved efficiency," Dr. Wu said. "This approach will facilitate the implementation of the knowledge based radiation therapy planning in clinics."

Knowledge-based planning enables clinicians to extract information from past clinical experience and use it to generate mathematical models that expedite the creation of new treatment plans. The software helps the planner quickly generate a new treatment plan that achieves the physician’s tumor coverage and normal tissue sparing goals, greatly reducing the need for time-consuming, manual trial-and-error processes while still optimizing quality.

"Varian’s RapidPlan software is a very robust knowledge-based planning solution that was developed to help clinical teams enhance quality, consistency, and efficiency in radiotherapy treatment planning," said Kolleen Kennedy, president of Varian Oncology Systems. "We are gratified to see research being conducted and presented, affirming the value of this tool for enhancing access to quality cancer treatment around the world. With the publication in the Lancet, last month, of a special report on the need to expand global access to radiotherapy, Varian is pleased to be offering tools like RapidPlan designed to improve utilization of radiotherapy around the world." [4]