Karyopharm drug tested in industry-first approach to brain cancer

Pharmaphorum | July 12, 2019

Karyopharms new drug Xpovio is to be tested in a new type of clinical trial designed to rapidly select individualised treatment combinations for brain cancer. The unusual phase 0/2 design starts with a preclinical phase in which Xpovio (selinexor) will be tested as part of several drug cocktails for glioblastoma – on a patient-by-patient basis – by scientists from the Ivy Brain Tumor Center in Phoenix, Arizona. Selinexor – a first-in-class oral XPO1 inhibitor – will initially be given alongside various other new experimental drugs to see which combinations have the greatest potential in the study, described as an ‘industry-first approach’ to drug testing. The tissue-based testing design can show if a combination is having an impact on a patient’s tumour in as little as seven days, allowing patients to quickly continue onto an advanced trial or switch to a different treatment, says Nader Sanai, a neurosurgical oncologist and director of the Ivy Centre. Glioblastoma – the cancer that killed US Senators John McCain and Ted Kennedy – is one of the deadliest types of cancer with a median survival of just 14 months, and has proved to be one of the toughest challenges for drug developers. According to the Ivy Centre, only five drugs have been approved for brain cancer patients in the US since 1982, while in the same timeframe more than 50 have been approved to treat lung cancer patients. Xpovio is variously described as a selective inhibitor of nuclear export (SINE) or an ‘exportin’ inhibitor, forcing tumour suppressor proteins such as p53 and p27 to be retained and accumulate in the cell nucleus, resulting in cell death. It was approved to treat multiple myeloma earlier this month – despite a call for a delay by an FDA advisory committee – and is also in mid- and late-stage testing in lymphoma as well as solid tumours such as liposarcoma and endometrial cancer. It’s already in a phase 2 trial as a second-line monotherapy in relapsed or refractory glioblastoma patients. Results in 30 subjects presented at the ASCO congress in June showed that the drug was able to achieve a 10% response rate – including one complete response and two partial responses. While not impressive at first glance, that is around twice what has been achieved with other drugs and 19% of the group had progression-free survival of six months.

Spotlight

A drug policy researcher for the University of Victoria, Alan Cassels is a known for having a knack for finding and describing the chasm between what the market says and what science does in modern healthcare. Over the past two decades Cassels has spent much of his research energy studying clinical research and the marketing tactics of the pharmaceutical industry, turnin

Spotlight

A drug policy researcher for the University of Victoria, Alan Cassels is a known for having a knack for finding and describing the chasm between what the market says and what science does in modern healthcare. Over the past two decades Cassels has spent much of his research energy studying clinical research and the marketing tactics of the pharmaceutical industry, turnin

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TherapeuticsMD Announces Definitive Agreements to License its Products to Mayne Pharma

TherapeuticsMD, Inc. | December 05, 2022

TherapeuticsMD, Inc. an innovative, leading women’s healthcare company, announced that it has entered into definitive agreements to license its products to an affiliate of Mayne Pharma Group Limited an ASX-listed specialty pharmaceutical company focused on commercializing novel and generic pharmaceuticals, for commercialization in the United States. In addition, TXMD has agreed to sell certain assets to Mayne Pharma to allow Mayne Pharma to commercialize the products. At closing of the transaction, TXMD will receive an upfront cash payment of $140.0 million for the license grant and sale of certain assets, plus an additional approximately $13.1 million, subject to customary adjustments, for acquired net working capital. In addition, TXMD will receive a 20-year royalty stream tied to Mayne Pharma’s net sales of the products. The upfront payment to be made by Mayne Pharma, along with cash on hand, will allow TXMD to repay its outstanding indebtedness with Sixth Street Partners and to redeem its outstanding preferred equity, with TXMD continuing as a pharmaceutical royalty company with the potential to create value for stakeholders over time from the resulting net cash flows. "After completing a thorough evaluation of several strategic alternatives, our Board of Directors concluded that this transaction with Mayne Pharma would create the most value for TherapeuticsMD’s stakeholders. This transaction will allow us to repay in full our debt to Sixth Street Partners and redeem our preferred stock from Rubric Capital Management, while also establishing a future royalty revenue stream for our common shareholders. We believe that Mayne Pharma has the experience necessary to fully realize the promise of our products as we work together to improve patient care.” The Honorable Tommy Thompson, Executive Chairman of TherapeuticsMD Upon completion of the transaction, which is subject to expiration or termination of the waiting period under the Hart-Scott-Rodino Act of 1976, Mayne Pharma will be responsible for development, regulatory filings, manufacturing, and commercialization of the Products. TXMD will receive an upfront payment of $140.0 million for the sale of the assets and the grant of the licenses, plus a payment of approximately $13.1 million for the acquisition of net working capital, subject to certain customary adjustments. In addition, Mayne Pharma will make one-time, milestone payments to the Company of (i) $5.0 million if aggregate net sales of all Products in the United States during a calendar year reach $100.0 million, (ii) $10.0 million if aggregate net sales of all Products in the United States during a calendar year reach $200.0 million and $15.0 million if aggregate net sales of all Products in the United States during a calendar year reach $300.0 million. Further, Mayne Pharma will pay to the Company royalties on net sales of all licensed Products in the United States at a royalty rate of 8.0% on the first $80.0 million in annual net sales and 7.5% on annual net sales above $80.0 million, subject to certain adjustments, for a period of 20 years following the closing. The royalty rate will decrease to 2.0% on a Product-by-Product basis upon the earlier to occur of the expiration or revocation of the last patent covering a Product and a generic version of a Product launching in the United States. Mayne Pharma will pay to the Company minimal annual royalties of $3.0 million per year for 12 years, adjusted for inflation at an annual rate of 3%, subject to certain further adjustments. In connection with entering into the transaction, the lenders and administrative agent under the Company’s Financing Agreement with Sixth Street Partners have agreed to extend the maturity date of the Financing Agreement to December 31, 2022, allowing the Company to complete the transaction with Mayne Pharma on or before that date. The maturity date of the Financing Agreement may be further extended to January 31, 2023, upon payment of an amendment fee, in the event the definitive agreements in connection with the transaction remain in effect and the waiting period under the HSR Act has not expired or terminated. The Company will retain its existing licensing agreements with Knight Therapeutics, Inc. and Theramex HQ UK Limited. The transaction is not subject to any financing conditions and is expected to close at the end of 2022, pending satisfaction of customary closing conditions. About TherapeuticsMD, Inc. TherapeuticsMD, Inc. is an innovative, leading healthcare company, focused on developing and commercializing novel products exclusively for women. TherapeuticsMD’s products are designed to address the unique changes and challenges women experience through the various stages of their lives with a therapeutic focus in family planning, reproductive health, and menopause management. TherapeuticsMD is committed to advancing the health of women and championing awareness of their healthcare issues.

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Pfizer Completes Acquisition of Biohaven Pharmaceuticals

Pfizer and Biohaven Pharmaceuticals | October 04, 2022

Pfizer Inc. announced the completion of its acquisition of Biohaven Pharmaceutical Holding Company Ltd., the maker of NURTEC® ODT an innovative migraine therapy approved for both acute treatment and prevention of episodic migraine in adults. The acquisition brings to Pfizer a portfolio of promising calcitonin gene-related peptide receptor antagonists including Rimegepant Approved in the United States under the trade name NURTEC® ODT, in adults for both the acute treatment of migraine with or without aura and the preventive treatment of episodic migraine Approved in the European Union under the trade name VYDURA® for both the acute treatment of migraine with or without aura in adults and the preventive treatment of episodic migraine in adults who have at least 4 migraine attacks per month Zavegepant New Drug Application for intranasal spray for the acute treatment of migraine under U.S. Food and Drug Administration review, with a Prescription Drug User Fee Act goal date in 1Q 2023 "We are proud to build on Pfizer’s legacy of delivering breakthrough medicines for patients living with complex pain disorders. The success of NURTEC® ODT coupled with Biohaven’s CGRP pipeline will strengthen Pfizer’s innovative Internal Medicine pipeline through 2030, and beyond. Combined with Pfizer’s global reach, this acquisition increases our potential to bring new treatment options to patients with migraine – a disease which affects over 1 billion people worldwide. Aamir Malik, Executive Vice President, Chief Business Innovation Officer, Pfizer Pfizer acquired all of the outstanding shares of Biohaven not already owned by Pfizer for $148.50 per share in cash, for a total transaction consideration of approximately $11.6 billion. As a result of the acquisition, Biohaven became a wholly-owned subsidiary of Pfizer. Effective immediately prior to the closing of the acquisition, Biohaven completed the spin-off of Biohaven Ltd. distributing Biohaven Ltd.’s shares to Biohaven’s shareholders. Biohaven Ltd., a new company that retained Biohaven’s non-CGRP development stage pipeline compounds, holds the Kv7 ion channel activators, glutamate modulation, and myostatin inhibition platforms, preclinical product candidates, and certain corporate infrastructure assets excluded from the Pfizer acquisition. Pfizer, a Biohaven shareholder, received a pro rata portion of Biohaven Ltd.’s shares in the distribution and owns approximately 3% of Biohaven Ltd. Biohaven Ltd. will continue to trade on the New York Stock Exchange under the ticker “BHVN”. About Migraine Worldwide, more than one billion people suffer from migraine, which predominately affects women.i Findings from the 2019 Global Burden of Disease study indicate that migraine is one of the worlds leading causes of disability.ii Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity that can be associated with nausea or vomiting, and/or sensitivity to sound and sensitivity to light. About Rimegepant Rimegepant targets a key component of migraine by reversibly blocking CGRP receptors, thereby inhibiting the biologic cascade that results in a migraine attack. Rimegepant was approved by the U.S. Food and Drug Administration (FDA) under the trade name Nurtec® ODT for the acute treatment of migraine in adults in February 2020 and for the preventive treatment of episodic migraine in adults in May 2021. Nurtec® ODT is taken orally as needed, up to once daily for acute treatment, and every other day for preventive treatment. The maximum dose in a 24 hour period is 75 mg. About Zavegepant Zavegepant is a third generation, high affinity, selective and structurally unique, small molecule CGRP receptor antagonist from the NOJECTION® Migraine Platform and the only CGRP receptor antagonist in clinical development with both intranasal and oral formulations. The FDA has accepted for review a New Drug Application (NDA) for zavegepant nasal spray, with a PDUFA date in 1Q 2023. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us.

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Sirona Biochem Signs International Partnership Agreement with Wanbang Biopharmaceuticals

Sirona Biochem Corp. | November 28, 2022

Sirona Biochem Corp. announces that, subsequent to the LOI, Sirona and Wanbang Biopharmaceuticals have signed an expanded, international partnership agreement to collaborate on licencing Sirona’s SGLT2 inhibitor, TFC-039, as a pharmaceutical treatment in both animal and human health. The agreement adds human health to the partnership as a result of new licencing opportunities currently in due diligence. Wanbang and Sirona initially signed a licensing agreement for TFC-039, whereby Wanbang obtained the rights to develop the compound as a diabetes treatment in China and Sirona retained the global rights. Sirona has since been in discussions with animal health companies to advance TFC-039 as a treatment for diabetes and chronic kidney disease in companion animals. SGLT2 inhibitors provide an opportunity to treat inflicted animals with an oral medication as opposed to the traditional method of daily insulin injections. More recently, Sirona has entered into due diligence with a large pharmaceutical company with a regional interest in developing the compound for human diabetes. Together, Sirona and Wanbang share extensive knowledge and scientific results of TFC-039. Partnering will significantly increase the speed to third-party partnerships and commercialization. The shared data spans over 12 years of research and development, and includes in vitro and in vivo preclinical work, multiple clinical studies, advanced manufacturing process development and the ability to commercially manufacture TFC-039. “We have a long-standing relationship with Wanbang and are excited to combine our two companies’ expertise to license TFC-039. Wanbang has invested millions of dollars into the clinical stage research and development of the manufacturing processes for TFC-039. These pieces of data are critical to large organizations and will greatly increase the opportunities to move forward. The probability of a successful licensing agreement has been made much stronger by leveraging our alliance with Wanbang. We have had a successful year building Sirona’s pipeline, with positive movement on all projects and we’re looking forward to continuing this success with our SGLT2 inhibitor as well as our antiviral and anti-aging projects in 2023.” Dr. Howard Verrico, CEO About Wanbang Biopharmaceuticals and Fosun Pharmaceuticals Wanbang Biopharmaceuticals develops, manufactures, and markets drugs with indications for chronic disease treatment, antibiotics, and other endocrine diseases in China. Founded in 1981, the company is headquartered in Xuzhou, China, and is a subsidiary of Shanghai Fosun Pharmaceutical Group. Fosun is a leader in the pharmaceutical industry and is regarded as one of the top five domestic pharmaceutical companies in China. About Sirona Biochem Corp. Sirona Biochem is a cosmetic ingredient and drug discovery company with a proprietary platform technology. Sirona specializes in stabilizing carbohydrate molecules with the goal of improving efficacy and safety. New compounds are patented for maximum revenue potential. Sirona’s compounds are licensed to leading companies around the world in return for licensing fees, milestone fees and ongoing royalty payments. Sirona’s laboratory, TFChem, is located in France and is the recipient of multiple French national scientific awards and European Union and French government grants.

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