Medicare Releases Final Local Coverage Determination Providing Coverage of Optune® for Newly Diagnosed Glioblastoma

On July 18, 2019 Novocure (NASDAQ: NVCR) reported the Medicare durable medical equipment (DME) Medicare Administrative Contractors (MACs) have released a final local coverage determination (LCD) providing coverage of Optune for Medicare beneficiaries with newly diagnosed glioblastoma (GBM) effective September 1, 2019 (Press release, NovoCure, JUL 18, 2019, View Source [SID1234537601]). The final LCD and a summary response to comments are available in the U.S. Centers for Medicare & Medicaid Services (CMS) coverage database.

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"We are extremely pleased that CMS has established coverage of Optune for patients with newly diagnosed GBM and that many of the restrictions originally proposed were removed in response to public comment," said Bill Doyle, Novocure’s Executive Chairman. "The FDA approved Optune for patients with newly diagnosed GBM following a large phase 3 clinical trial that demonstrated adding Optune to temozolomide extends survival while maintaining quality of life. Novocure is committed to providing access to Optune for all patients who may benefit, consistent with the FDA-approved label."

The coverage criteria finalized by the DME MACs is generally similar to Optune’s commercial coverage criteria for newly diagnosed GBM. According to the LCD, Optune will be covered initially by Medicare when the following criteria are met:

The beneficiary has histologically confirmed (World Health Organization (WHO) grade IV astrocytoma), newly diagnosed, supratentorial GBM; and,
The beneficiary has received initial treatment with maximal debulking surgery (when feasible), followed by chemotherapy and radiotherapy; and,
Optune is initiated within 7 weeks from the last dose of concomitant chemotherapy or radiotherapy, whichever is later; and,
The beneficiary has no evidence of progression by Response Assessment in Neuro-Oncology (RANO) criteria; and,
The beneficiary has a Karnofsky Performance Score (KPS) of at least 70; and,
The beneficiary will use Optune for an average of 18 hours per day. (Adherence to therapy is defined as the use of Optune for an average of 18 hours per day excluding days the treating practitioner has documented a medical need to limit or interrupt treatment.)
For beneficiaries who are undergoing treatment with Optune for newly diagnosed GBM prior to enrollment in Fee-For-Service (FFS) Medicare and are seeking Medicare coverage for Optune, the LCD states that Optune will be covered by Medicare when the following criteria are met:

The beneficiary has been receiving Optune following initial maximal debulking surgery (if feasible) followed by chemotherapy/radiotherapy for histologically confirmed newly diagnosed GBM; and,
Following enrollment in FFS Medicare, the beneficiary must have a face-to-face evaluation by their treating practitioner who documents in the beneficiary’s medical record that the beneficiary is adherent with Optune for an average of 18 hours per day and the beneficiary is deriving benefit from the therapy.
Approved Indications

Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM).

Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial glioblastoma following maximal debulking surgery, and completion of radiation therapy together with concomitant standard of care chemotherapy.

For the treatment of recurrent GBM, Optune is indicated following histologically- or radiologically-confirmed recurrence in the supratentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.

The NovoTTF-100L System is indicated for the treatment of adult patients with unresectable, locally advanced or metastatic, malignant mesothelioma (MPM) to be used concurrently with pemetrexed and platinum-based chemotherapy.

Important Safety Information

Contraindications

Do not use Optune in patients with GBM with an implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune ineffective. Do not use the NovoTTF-100L System in patients with MPM with implantable electronic medical devices such as pacemakers or implantable automatic defibrillators, etc.

Use of Optune for GBM or the NovoTTF-100L System for MPM together with implanted electronic devices has not been tested and may lead to malfunctioning of the implanted device.

Do not use Optune for GBM or the NovoTTF-100L System for MPM in patients known to be sensitive to conductive hydrogels. Skin contact with the gel used with Optune and the NovoTTF-100L System may commonly cause increased redness and itching, and may rarely lead to severe allergic reactions such as shock and respiratory failure.

Warnings and Precautions

Optune and the NovoTTF-100L System can only be prescribed by a healthcare provider that has completed the required certification training provided by Novocure.

The most common (≥10%) adverse events involving Optune in combination with chemotherapy in patients with GBM were thrombocytopenia, nausea, constipation, vomiting, fatigue, convulsions, and depression.

The most common (≥10%) adverse events related to Optune treatment alone in patients with GBM were medical device site reaction and headache. Other less common adverse reactions were malaise, muscle twitching, and falls related to carrying the device.

The most common (≥10%) adverse events involving the NovoTTF-100L System in combination with chemotherapy in patients with MPM were anemia, constipation, nausea, asthenia, chest pain, fatigue, device skin reaction, pruritus, and cough.

Other potential adverse effects associated with the use of the NovoTTF-100L System include: treatment related skin toxicity, allergic reaction to the plaster or to the gel, electrode overheating leading to pain and/or local skin burns, infections at sites of electrode contact with the skin, local warmth and tingling sensation beneath the electrodes, muscle twitching, medical site reaction and skin breakdown/skin ulcer.

If the patient has an underlying serious skin condition on the treated area, evaluate whether this may prevent or temporarily interfere with Optune and the NovoTTF-100L System treatment.

Do not prescribe Optune or the NovoTTF-100L System for patients that are pregnant, you think might be pregnant or are trying to get pregnant, as the safety and effectiveness of Optune and the NovoTTF-100L System in these populations have not been established.

Kronos Bio Completes $105 Million Series A Financing

On July 18, 2019 Kronos Bio, Inc. (Kronos), a Two River portfolio company, reported it has closed a $105 million Series A Preferred Stock financing (Press release, Kronos Bio, JUL 18, 2019, View Source [SID1234537600]). The financing was led by Vida Ventures, LLC and Omega Funds and included participation from Nextech, GV (formerly Google Ventures), Perceptive Advisors, Invus and Polaris Partners. This Series A round also included significant participation from Kronos’ President and Chief Executive Officer, Norbert Bischofberger, Ph.D. as well as members of the Board of Directors including Arie Belldegrun, M.D., FACS and John Martin, Ph.D. In conjunction with this financing, Jakob Loven, Ph.D., Partner at Nextech, will join the Board of Directors of Kronos Bio.

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Kronos’ Small Molecule Microarray platform (SMM) was built on more than a decade of research by its scientific founder, Angela Koehler, Ph.D., Associate Professor of Biological Engineering at the Massachusetts Institute of Technology. SMM is ideally suited for the rapid discovery of novel modulators or degraders of historically undruggable targets, such as transcription factors. Kronos has demonstrated SMM’s potential to identify compounds that bind to target proteins directly or interfere at nanomolar potency with protein activity. SMM enables discovery of hits that act through a variety of mechanisms, including disruption of protein-protein or protein-DNA interactions, or indirect modulation of target protein activity by binding to co-factors or other protein complex members.

"We are excited to have the continued support of high caliber investors who recognize the potential of Kronos’ technology and its team. This financing will help us advance two preclinical programs built upon hits identified from SMM screens, accelerate our research, and further expand the Kronos team in the Boston and San Francisco areas," said Norbert Bischofberger, Ph.D., President and Chief Executive Officer of Kronos. "We seek to challenge the historic belief that certain targets cannot be pursued. Our goal is to unlock new therapeutic approaches and bring treatments to areas with high unmet need."

Existing therapies target only a minority of the body’s proteins, which are well-structured and accessible to traditional small molecule approaches. The majority of proteins, however, are disordered or lack obvious binding pockets and have historically been considered undruggable. Kronos’ platform enables high-throughput screens of chemical libraries against such target proteins in a more physiologically relevant context to identify biologically active small molecules.

"When we founded Kronos at Two River, we identified early on the need for support by investors who embrace cutting edge innovation," said Joshua Kazam, a Kronos Board Member and a Director at Vida Ventures. "With this Series A round, we have expanded support with investors equally as passionate about funding scientific breakthroughs to impact how we treat some of the most challenging diseases we face today."

"Since our initial investment, we have been very excited about the opportunity to identify novel therapies provided by the Kronos platform: we believe this is a huge opportunity not just for investors but more importantly, for addressing unmet needs in hard-to-treat diseases," said Otello Stampacchia, Ph.D., a Kronos Board Member and Founder and Managing Director of Omega Funds. "We are delighted to co-lead this milestone Series A financing and to be a part of the Kronos Bio team in this journey."

Transgene Receives MHRA Approval for a Clinical Trial of TG6002, a Next-generation Oncolytic Virus, Administered by Intrahepatic Artery Infusion in Patients with Colorectal Cancer with Liver Metastases

On July 18, 2019 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported it has received the approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to proceed with a Phase 1/2a clinical trial of TG6002 administered by intrahepatic artery (IHA) infusion in colorectal cancer patients with unresectable liver metastases (CRLM) (Press release, Transgene, JUL 18, 2019, View Source [SID1234537599]).

TG6002 is a next-generation oncolytic virus (OV), which has multiple mechanisms of action. It has been engineered to combine the killing of cancer cells (oncolysis), the production of 5-FU, a widely used chemotherapeutic agent, in the tumor site, and the eliciting of an immune response against tumor cells. TG6002 expresses the proprietary FCU1 gene in the cancer cells it has infected, leading to local conversion of the pro-drug 5-FC (administered orally) into 5-FU. This is particularly important as most gastrointestinal tumors are 5-FU sensitive. TG6002 has been shown to induce both response in the primary tumor and an immune-mediated regression of distant metastases in preclinical experiments1.

"Current systemic therapies prolong survival of CRLM patients at the cost of significant side effects. We believe that TG6002 therapy administered via an IHA infusion potentially offers an additional effective and well tolerated treatment modality for these difficult to treat patients. By administering it via the intrahepatic artery, we believe we can conveniently deliver more concentrated doses of TG6002 to the tumor, to achieve better outcomes for unresectable colorectal cancer, whilst limiting systemic exposure. In parallel, Transgene is conducting a Phase 1/2 trial to investigate TG6002 in colorectal cancer patients when given intravenously," said Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

Dr. Adel Samson, MB ChB PhD, Medical Oncologist at St. James’ University Hospital, is the Chief Investigator of the trial.
This trial is a single-arm open-label Phase 1/2a trial evaluating the safety, pharmacokinetics and efficacy of repeated and ascending doses of TG6002 administered by IHA route in combination with oral 5-FC, a non-cytotoxic pro-drug that can be converted in 5-FU. The study is expected to start in Q4 2019 and could enroll up to 75 patients.

— End–

About TG6002
TG6002 is a next generation oncolytic immunotherapy. It has been designed to induce the breakdown of cancer cells (oncolysis) and allow the local production of chemotherapy (5-FU) in the tumor. TG6002 is a modified Vaccinia virus, with double gene deletion (TK-RR-), and expressing the proprietary FCU1 gene in the cancer cells it has infected, leading to the local conversion of the non-cytotoxic pro-drug, flucytosine (5-FC), into 5-FU, a widely used cancer chemotherapy. The oncolytic virus TG6002 has shown efficacy and good safety profile in several preclinical models. Transgene believes that TG6002 may represent a new therapeutic option in recurrent cancer patients.
Another Phase 1/2 trial using TG6002 administered intravenously is ongoing in Europe in patients with advanced gastrointestinal tumors.

About Colorectal cancer
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Europe and a leading cause of death both in Europe and worldwide. In 2012, there were 447,000 new cases of CRC in Europe with 215,000 deaths and worldwide, there were 1.4 million new cases with 694,000 deaths (Ferlay J. et al., 2013, Ferlay J. et al., 2015). Approximately half of all CRC patients develop liver metastases, only a small proportion of whom being suitable for potentially curative hepatic resection (Leporrier J, 2006). Over the last decade, the clinical outcome for patients with metastatic CRC (mCRC) has improved. Today, the median overall survival (OS) for patients with mCRC is ∼30 months.

Iovance Biotherapeutics Appoints Friedrich Graf Finckenstein, M.D., as Chief Medical Officer

On July 18, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported the appointment of Friedrich Graf Finckenstein, M.D., as chief medical officer (Press release, Iovance Biotherapeutics, JUL 18, 2019, View Source [SID1234537598]). Dr. Graf Finckenstein brings over 19 years of experience in clinical development and translational research to the company.

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"We are very pleased to have Dr. Finckenstein join Iovance as we move forward with pivotal studies for lifileucel in metastatic melanoma and LN-145 in metastatic cervical cancer," said Maria Fardis, Ph.D., president and chief executive officer of Iovance Biotherapeutics. "Dr. Finckenstein’s experience with prior approval of checkpoint therapy as well as his breadth of involvement with translational medicine will be of great value to Iovance while we progress our late-stage development programs toward commercialization and expand the utility of TIL in new indications."

"I am very pleased to be part of a dedicated team working on bringing a novel cell therapy to patients with very limited approved therapeutic options," commented Friedrich Graf Finckenstein, M.D. "I’m excited to be able to contribute to development of TIL therapy as we work on the important next steps involved in preparing for regulatory submission."

Dr. Graf Finckenstein is a physician-scientist with decades of experience in clinical medicine, laboratory cancer research, and drug development in the biopharmaceutical industry. Prior to joining Iovance he was Global Head of Oncology Translational Medicine at Roche Pharma Research and Early Development (pRED) in Basel, Switzerland, where he led all clinical development aspects in the Oncology Discovery and Translational Area, including the design and conduct of clinical trials, exploratory development studies and translational medicine, biomarker and personalized healthcare strategy. Prior to that, Dr. Graf Finckenstein held multiple clinical leadership roles at Bristol-Meyers Squibb Company, where he worked on an array of products from early clinical development to late stage, including key contributions to the approval of Opdivo in lung cancer. Dr. Graf Finckenstein has a medical degree from the University of Hamburg in Germany. He holds a German medical license, a pediatric board certification, and has conducted basic cancer research at the Ludwig Institute, San Diego Branch, the Children’s Hospital Los Angeles and the University of Hamburg.

Immunocore and Pulse Infoframe, Inc. Partner with Leading Academic Institutions to Launch First Global Patient Registry for Uveal Melanoma

On July 18, 2019 Immunocore Limited, a leading T cell receptor biotechnology company, and Pulse Infoframe, Inc. (Pulse), a data aggregation and analytics company, reported plans to support the first global patient registry in uveal melanoma (UM), a rare and aggressive form of melanoma, which affects the eye, typically has a poor prognosis and for which there is no currently accepted optimal management or treatment (Press release, Immunocore, JUL 18, 2019, View Source [SID1234537597]).1 The insights gained through the academic registry will provide a more comprehensive understanding of the disease and may help to shape the way future research is conducted.

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The registry will include institutions from across the US, UK and Australia, and is currently being developed by leaders in the field of uveal melanoma, including:

Richard Carvajal, MD, Director of Experimental Therapeutics and Director of the Melanoma Service at Columbia University Medical Center, Columbia University, US
Joseph Sacco, PhD, Clinical Senior Lecturer at the University of Liverpool and Honorary Consultant in Medical Oncology at Clatterbridge Cancer Centre, UK
Anthony Joshua, MBBS, PhD, Director of Cancer Services at St Vincent’s Hospital and conjoint Associate Professor with the University of New South Wales, Australia
"The rarity of uveal melanoma makes it difficult to collect the data needed to better understand how the disease manifests and evolves, and who is likely to respond to treatment and why," said Dr. Carvajal. "For the first time we’ll have the opportunity to prospectively collect and analyse global real-world data, including patient-reported outcomes. This will help to guide medical research, innovative trial design and recruitment, potentially paving the way for accelerated treatment advances."

Research generated from the registry will examine risk factors, genetics, epidemiology, treatment cost-effectiveness and real-world outcomes from a database of patients with uveal melanoma. The goal is to create a benchmark framework, or ecosystem, for collecting and assessing clinical outcomes, as well as providing necessary data for future genetic, sub-phenotype and biomarker research.

"We’re excited to be working with the research community to address the need for a more comprehensive understanding of uveal melanoma," said Mohammed Dar, MD, Head of Clinical Development and Chief Medical Officer at Immunocore. "We believe that this registry will provide critical insight that may help to advance the development of future treatments, including clinical and genetic information about potential subsets of people living with this devastating disease."

Enrolment into the registry is expected to begin in August at five sites in the US, three sites in the UK, and three sites in Australia.

"At Pulse, we strive to support the entire ecosystem that researchers, clinicians and patients require to generate the real-world evidence necessary to advance clinical outcomes, support patient advocacy and promote disease awareness," said Femida Gwadry-Sridhar, RPh, PhD, CEO and Founder at Pulse. "We are pleased to partner with Immunocore and key academic leaders on this patient registry, which will provide a detailed look into uveal melanoma from a global perspective."

About Uveal Melanoma

Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye, typically has a poor prognosis and for which there is no currently accepted optimal management or treatment.1 Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, with approximately 8,000 new patients diagnosed globally each year (1,600-2,000 cases/year in the US).1,2,3,4 Up to 50% of people with uveal melanoma will eventually develop metastatic disease.1 When the cancer spreads beyond the eye, only approximately 40% of patients will survive for one year.1