Clementia Pharmaceuticals, Inc.

Ipsen considered palovarotene "de-risked" and ready for approval when it acquired the drug in a 2019 deal for $1 billion. Four years later, after clearing many hurdles, the French company has won FDA approval for the rare disease drug. When Ipsen ponied up $1 billion in 2019 to acquire Clementia Pharmaceuticals for its rare disease drug palovarotene, the Paris-based company referred to the asset as “largely de-risked.” Four years, two clinical trial holds, a complete response letter, a European Commission rejection, a scrapped trial in another indication and multiple safety flags, resubmissions and delays later, Ipsen finally has gotten checkered palovarotene across the FDA finish line. Wednesday, the U.S. regulator signed off on Sohonos, an oral medication to treat the ultra-rare bone disease fibrodysplasia ossificans progressive (FOP) in females ages 8 and older and males ages 10 and older. Sohonos is a retinoic acid receptor gamma agonist that curbs progression of the genetic disease by reducing the volume of new, abnormal bone growth. FOP, which affects roughly 400 people in the U.S., causes loss of mobility, leaving most patients in a wheelchair by age 30 and reducing life expectancy to age 56. Many die from respiratory failure caused by excessive bone formation around the rib cage, Ipsen’s R&D chief Howard Mayer, M.D., said in an interview. “This is a really important moment in that it actually provides the first therapy available for patients with FOP,” Mayer said. Paving the way for approval were data from a phase 3 trial that showed Sohonos reduced new bone growth by 54%. The treatment will carry a boxed warning for children outlining the risk of premature closure of growth plates, which can cause bone deformities and stunted growth. There also is a warning for embryo-fetal toxicity. Ipsen will charge $624,000 annually for a 5-mg daily dose, the company told Reuters, though dosage will depend on disease severity and the weight of a patient, Mayer said. The company could eventually face competition in the indication from Regeneron. That company's pipeline drug is set up for an FDA submission next year. Along with the approval, Ipsen receives a priority review voucher, which it can sell or use to speed the processing of a subsequent FDA application. Roche developed palovarotene but sold its worldwide rights to Canadian company Clementia in 2013 after the treatment flunked a phase 2 trial in emphysema. The fortunes of palovarotene changed when a phase 2 trial in FOP set it up for an FDA submission in 2019. But soon after Ipsen acquired Clementia, the FDA put two clinical trials of palovarotene on partial clinical holds because of safety concerns. The situation went from bad to worse in the first quarter of 2020, when an interim analysis found the phase 3 trial in FOP was unlikely to meet its primary endpoint.  Two months later, Ipsen scrapped a pivotal trial in a second, potentially more lucrative indication because the pause in dosing under the clinical hold may have compromised the integrity of the data. Between the setbacks, Ipsen recorded a 669 million euro impairment charge. But through post hoc analysis in the FOP trial, Ipsen found a potential route to approval. While the new approach won over regulators in Canada in 2022, it got a final thumbs-down in Europe last month. In October of last year, the FDA was set to assemble an advisory committee to discuss palovarotene but canceled the meeting and asked Ipsen for additional data. Two months later, the regulator rejected Ipsen’s application for approval. Early this year, Ipsen provided the needed data, and a lengthy June advisory committee meeting produced a 10-4 vote in favor of approval. “There were many surprises,” Mayer said of Ipsen’s initial struggles with palovarotene. “It’s been an obstacle course. But we really followed the science for the benefit of patients and worked collaboratively with FDA.”

Dive Brief:After years of fits and starts, Ipsen won Food and Drug Administration approval to sell the first treatment for a rare disease known as fibrodysplasia ossificans progressiva, or FOP.The FDA cleared the drug, palovarotene, for females who are least 8 years old and males at least 10 years old, Ipsen said Wednesday. Its designed to reduce the formation of bone in tissue that is characteristic of the debilitating condition.Ipsen will sell the medicine under the brand name Sohonos at an average list price of $624,000 a year, though the cost will vary depending on insurance coverage, patient needs and support programs. A company spokeswoman said Ipsen is committed to making the treatment accessible to the approximately 400 people in the U.S. who have the disease.Dive Insight:The road to the U.S. market has been a winding one for Sohonos and Ipsen. Roche originally developed the medicine as a treatment for chronic obstructive pulmonary disease, but it failed in testing. The Canadian biotech Clementia Pharmaceuticals then licensed the medicine and in 2014 won orphan drug and fast track designations from the FDA to help speed development for FOP.The initial studies went well enough to attract the attention of Ipsen, which agreed in 2019 to buy Clementia for as much as $1.3 billion. But clinical trials delivered mixed results for Ipsen, and the FDA rejected the drug in late 2022. Ipsen tried again in March with new analyses of previous research, a gambit that doesnt always fly with regulators.An FDA advisory committee backed the drug in June, even though agency reviewers raised questions about its effectiveness and the potential for the treatment to cause inflammatory flare-ups. The final approval granted Wednesday came with a priority review voucher, which Ipsen can sell or use to speed the review process for another of its own drugs. The vouchers can fetch around $100 million when sold.Regulators in other parts of the world have had mixed views of the treatment. Canada approved the medicine in early 2022 and it also has conditional approval in the United Arab Emirates. But the European Commission last month decided against authorization.Even though FOP is exceedingly rare affecting only about 900 people around the world the condition has also drawn the interest of Regeneron Pharmaceuticals, which is testing a potential competing therapy in a Phase 3 trial. Ipsen also has a different option in Phase 2 that was acquired through the Clementia purchase. '

WALTHAM, Mass., Aug. 03, 2023 (GLOBE NEWSWIRE) -- Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced the promotion of Chris Frankenfield to chief operating officer of Xilio. “Chris has played an integral strategic leadership role in supporting the growth and evolution of Xilio as a clinical-stage company,” said René Russo, Pharm.D., chief executive officer of Xilio. “I look forward to partnering with Chris in his new role as he helps continue to drive Xilio’s key strategic initiatives to advance our pipeline of novel tumor-activated immuno-oncology treatments.” Mr. Frankenfield is an accomplished biotechnology executive with over 15 years of experience guiding companies on corporate strategy and operations, capital markets and business development transactions, corporate governance and IP strategy. Prior to becoming chief operating officer, Mr. Frankenfield served as Xilio’s chief legal and administrative officer from August 2022 to August 2023 and as general counsel from March 2021 to August 2022. In these roles, he has helped lead the execution of Xilio’s corporate and legal strategy as well as operations across multiple business functions. Prior to joining Xilio, Mr. Frankenfield served as vice president of corporate legal affairs at Blueprint Medicines and as a member of its management team. At Blueprint Medicines, he led public company reporting activities, advised on capital markets strategies, supported multiple successful equity offerings, and executed collaborations and partnerships with Roche and Genentech, CStone Pharmaceuticals and Clementia Pharmaceuticals, a wholly-owned subsidiary of Ipsen. Before Blueprint Medicines, Mr. Frankenfield was a senior associate at Wilmer Cutler Pickering Hale and Dorr LLP, with a focus on capital markets, strategic transactions, public company reporting and corporate governance matters. Mr. Frankenfield began his career at PricewaterhouseCoopers LLP, advising clients on complex commercial disputes and investigations. He received his B.A. in economics from the College of William & Mary and his J.D. from the University of Virginia School of Law. About Xilio Therapeutics Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary geographically precise solutions (GPS) platform to build a pipeline of novel, tumor-activated molecules, including cytokines and other biologics, which are designed to optimize their therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as programs in preclinical development. Learn more by visiting www.xiliotx.com and follow us on Twitter (@xiliotx) and LinkedIn (Xilio Therapeutics, Inc.). Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements related to plans, strategies, timelines and expectations for Xilio’s current or future product candidates; the potential benefits of any of Xilio’s current or future product candidates in treating patients; and Xilio’s strategy, goals and anticipated financial performance, milestones, business plans and focus. Each forward-looking statement is subject to important risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including, without limitation, the risks and uncertainties identified under the headings “Risk Factors Summary” and “Risk Factors” in Xilio’s filings with the U.S. Securities and Exchange Commission (SEC), including Xilio’s most recent Quarterly Report on Form 10-Q and any other filings that Xilio has made or may make with the SEC in the future. These forward-looking statements speak only as of the date of this press release. Factors or events that could cause Xilio’s actual results to differ may emerge from time to time. Xilio undertakes no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law. This press release contains hyperlinks to information that is not deemed to be incorporated by reference in this press release. For Investor and Media Inquiries: Julissa VianaVice President, Head of Investor Relations and Corporate Communicationsinvestors@xiliotx.com Melissa ForstArgot PartnersXilio@argotpartners.com