Deflazacort

– Strong revenue performance, supporting increase in full-year revenue guidance to $750-800 million – – Regulatory filings for sepiapterin, Translarna™ and AADC gene therapy under review by FDA – – On track to achieve remaining 2024 clinical and regulatory milestones, including NDA submission for vatiquinone – WARREN, N.J., Nov. 7, 2024 /PRNewswire/ -- PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced a corporate update and financial results for the third quarter ending September 30, 2024. "I am proud of our team's strong execution," said Matthew Klein, M.D., Chief Executive Officer. "We continue to achieve excellent revenue performance allowing us to raise full-year revenue guidance. In addition, we have submitted three approval applications to FDA so far this year, all of which have been accepted for review, and plan a fourth submission for vatiquinone for Friedreich ataxia in December. We are on our way to accomplishing all of our 2024 objectives and are in a strong financial position to execute on our long-term strategic plans." Key Corporate Updates: Third quarter 2024 total revenue of $197 million Third quarter 2024 revenue for the DMD franchise was $124 million Translarna™ (ataluren) net product revenue was $72 million, driven by continued access for patients in existing geographies, continued geographic expansion, high compliance and adherence, and dose adjustments. Emflaza® (deflazacort) net product revenue was $52 million, driven by new patient starts, continued brand loyalty, high compliance and adherence, and dose adjustments. Key Clinical and Regulatory Milestones: PTC submitted an NDA to the FDA for sepiapterin for the treatment of PKU. The file was accepted for review, and the regulatory action date is set for July 29, 2025. PTC resubmitted the NDA for Translarna for the treatment of nmDMD; the file was accepted, and a regulatory action date was not provided. The BLA for PTC's gene therapy for AADC deficiency remains on schedule for a regulatory action date of November 13, 2024. PTC received Fast Track Designation for the PTC518 Huntington's disease program. PTC plans to submit an NDA for vatiquinone for the treatment of Friedreich ataxia in December 2024. PTC expects to share topline data for the CardinALS trial of utreloxastat for the treatment of ALS in the fourth quarter of 2024. Third Quarter 2024 Financial Highlights: Total revenues were $196.8 million for the third quarter of 2024, compared to $196.6 million for the third quarter of 2023. Total revenue includes net product revenue across the commercial portfolio of $135.4 million for the third quarter of 2024, compared to $144.0 million for the third quarter of 2023. Total revenue also includes royalty and manufacturing revenue of $61.4 million in the third quarter of 2024, compared to $52.5 million for the third quarter of 2023. Translarna net product revenues were $72.3 million for the third quarter of 2024, compared to $69.0 million for the third quarter of 2023. Emflaza net product revenues were $51.9 million for the third quarter of 2024, compared to $67.4 million for the third quarter of 2023. Roche reported Evrysdi® 2024 year-to-date sales of approximately CHF 1.2 billion, resulting in royalty revenue of $61.4 million to PTC for the third quarter of 2024, compared to $50.2 million for the third quarter of 2023. Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $161.4 million for the third quarter of 2024, compared to $164.2 million for the third quarter of 2023. The decrease in research and development expenses reflects strategic portfolio prioritization, as PTC continues to focus its resources on its differentiated, high-potential R&D programs. Included in third quarter 2024 R&D expense is $50.0 million in regulatory success-based milestones related to the Censa acquisition. Non-GAAP R&D expenses were $152.0 million for the third quarter of 2024, excluding $9.4 million in non-cash, stock-based compensation expense, compared to $150.2 million for the third quarter of 2023, excluding $14.0 million in non-cash, stock-based compensation expense. GAAP SG&A expenses were $73.5 million for the third quarter of 2024, compared to $80.9 million for the third quarter of 2023. The decrease in selling, general and administrative expenses reflects lower employee costs as a result of the reduction in workforce in 2023. Non-GAAP SG&A expenses were $63.1 million for the third quarter of 2024, excluding $10.3 million in non-cash, stock-based compensation expense, compared to $67.9 million for the third quarter of 2023, excluding $13.0 million in non-cash, stock-based compensation expense. Change in the fair value of deferred and contingent consideration was a loss of $0.7 million for the third quarter of 2024, compared to a loss of $1.5 million for the third quarter of 2023. Tangible asset impairment and losses (gains) on transactions, net, was a loss of $1.8 million for the third quarter of 2024, compared to $0.0 million for the third quarter of 2023. These results were primarily related to fixed asset impairments. Net loss was $106.7 million for the third quarter of 2024, compared to net loss of $133.0 million for the third quarter of 2023. Cash, cash equivalents, and marketable securities was $1,013.4 million on September 30, 2024, compared to $876.7 million on December 31, 2023. Shares issued and outstanding as of September 30, 2024, were 76,952,124. PTC Updates Full Year 2024 Financial Guidance: PTC anticipates total revenues for full year 2024 to be between $750 million and $800 million. PTC anticipates GAAP R&D and SG&A expenses for full year 2024 to be between $740 million and $835 million, including expected R&D expense milestone payments of up to $65 million. PTC anticipates non-GAAP R&D and SG&A expenses for full year 2024 to be between $660 million and $755 million, including expected R&D expense milestone payments of up to $65 million and excluding estimated non-cash, stock-based compensation expense of $80 million. PTC anticipates up to $90 million of payments for full year 2024 upon achievement of potential regulatory success-based milestones from previous acquisitions, of which up to $65 million will be recorded as R&D operating expenses. As of September 30, 2024, $85 million in milestones have been achieved, of which $65 million has been recorded as R&D operating expenses and $20 million as contingent consideration payable. Non-GAAP Financial Measures: In this press release, the financial results of PTC are provided in accordance with GAAP and using certain non-GAAP financial measures. In particular, the non-GAAP R&D and SG&A expense financial measures exclude non-cash, stock-based compensation expense. These non-GAAP financial measures are provided as a complement to financial measures reported in GAAP because management uses these non-GAAP financial measures when assessing and identifying operational trends. In management's opinion, these non-GAAP financial measures are useful to investors and other users of PTC's financial statements by providing greater transparency into the historical and projected operating performance of PTC and the company's future outlook. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. Quantitative reconciliations of the non-GAAP financial measures to their respective closest equivalent GAAP financial measures are included in the table below. Acronyms: AADC: Aromatic l-Amino Acid Decarboxylase ALS: Amyotrophic Lateral Sclerosis BLA: Biologics License Application CHF: Confoederatio Helvetica Francs (Swiss francs) DMD: Duchenne Muscular Dystrophy FA: Friedreich Ataxia FDA: U.S. Food and Drug Administration GAAP: Generally Accepted Accounting Principles HD: Huntington's Disease NDA: New Drug Application nmDMD: Nonsense Mutation Duchenne Muscular Dystrophy PKU: Phenylketonuria R&D: Research and Development SG&A: Selling, General, and Administrative Today's Conference Call and Webcast Reminder: To access the call by phone, please click here to register and you will be provided with dial-in details. To avoid delays, we recommend participants dial in to the conference call 15 minutes prior to the start of the call. The webcast conference call can be accessed on the Investor section of the PTC website at . A replay of the call will be available approximately two hours after completion of the call and will be archived on the company's website for 30 days following the call. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to children and adults living with rare disorders. PTC's ability to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. The company's strategy is to leverage its strong scientific expertise and global commercial infrastructure to maximize value for its patients and other stakeholders. To learn more about PTC, please visit us at and follow us on Facebook, X, and LinkedIn. For More Information: Investors: Ellen Cavaleri +1 (615) 618-6228 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statements: This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including the information provided under the heading "PTC Updates Full Year 2024 Financial Guidance", including with respect to (i) 2024 total revenue guidance, (ii) 2024 GAAP and non-GAAP R&D and SG&A expense guidance and (iii) 2024 acquisition related milestone payment guidance, and statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; PTC's strategy, future operations, future financial position, future revenues, projected costs; the extent, timing and financial aspects of our strategic pipeline prioritization and reductions in workforce; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; PTC's ability to maintain its marketing authorization of Translarna for the treatment of nmDMD in Brazil, Russia, the European Economic Area (EEA) and other regions, including whether the European Commission adopts the negative opinion from the Committee for Medicinal Products for Human Use (CHMP) for the conditional marketing authorization for Translarna in the EEA, or PTC's ability to identify other potential mechanisms by which it may provide Translarna to nmDMD patients in the EEA; PTC's ability to use the clinical data from its international drug registry study and real-world evidence concerning Translarna's benefits to support a continued marketing authorization for Translarna for the treatment of nmDMD in the EEA; PTC's ability to use the results of Study 041, a randomized, 18-month, placebo-controlled clinical trial of Translarna for the treatment of nmDMD followed by an 18-month open-label extension, and from its international drug registry study to support a marketing approval for Translarna for the treatment of nmDMD in the United States; whether investigators agree with PTC's interpretation of the results of clinical trials and the totality of clinical data from its trials in Translarna; expectations with respect to Upstaza, including any regulatory submissions and potential approvals, commercialization, manufacturing capabilities, the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to sepiapterin, including any regulatory submissions and potential approvals, commercialization, the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to the commercialization of Evrysdi under PTC's SMA collaboration; expectations with respect to the commercialization of Tegsedi and Waylivra; the timing of and actual expenses incurred in connection with the discontinuation of PTC's preclinical and early research programs in gene therapy and reductions in workforce, which may be in different periods and may be materially higher than estimated; the savings that may result from the discontinuation of PTC's strategic pipeline prioritization and reductions in workforce, which may be materially less than expected; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; PTC's ability to satisfy its obligations under the terms of its lease agreements; the sufficiency of PTC's cash resources and its ability to obtain adequate financing in the future for its foreseeable and unforeseeable operating expenses and capital expenditures; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Translarna, Emflaza, Upstaza, Evrysdi, Tegsedi, Waylivra or sepiapterin. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. SOURCE PTC Therapeutics, Inc. 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The EU first gave Translarna a conditional marketing authorization in 2014 for the treatment of DMD, a progressive condition that causes the muscles to weaken, eventually becoming life-threatening. Eligible patients for the treatment are at least 2 years old, are able to walk, and their disease is caused by a so-called nonsense mutation in the protein dystrophin, which strengthens and protects muscle fibers The initial approval decision was weighted ​ by a lack of treatments for DMD and was contingent on further trials to confirm its benefits. However, two studies of Translarna after the authorization called 020 and 041 missed their efficacy goals. While a specific subgroup of patients in study 020 did show evidence of responding to the drug, patients in 041 saw no significant differences in the deterioration of their walking ability relative to those in the placebo group. The CHMP produced a negative opinion for Translarna in September 2023, which it confirmed in January 2024. The CHMP then went back into discussion in May this year when the European Commission requested that the committee consider the evidence in addition to more real-world data, but upheld the rejection. In July this year, PTC Therapeutics requested a re-evaluation of the treatment from the studies in addition to data from a different study comparing patients from different registries, which appeared to show a delay in disability in some treated patients. However, the CHMP once again declined, citing differences between the registries and biases. It also took into account third-party perspectives from patients and healthcare professionals. googletag.cmd.push(function () { googletag.display('text-ad1'); }); In a public statement ​, Matthew Klein, CEO of PTC Therapeutics, said the "CHMP again based its decision on the results of the primary analysis subpopulation of Study 041 instead of the totality of evidence for Translarna.” He later said that the decision “is clearly against the expressed wishes of physicians, patients and families throughout Europe.” The opinion will now be reviewed by the European Commission, which will make a legally binding decision within around two months. For now, Translarna is still commercially available and PTC is working to make sure the EC has the evidence it needs. Klein told Outsourcing Pharma that in discussions with FDA, the US regulator has been open to considering review of an NDA based on the totality of evidence, unlike the EMA’s CHMP. The DMD landscape There is no cure for DMD, with current treatments ​ including surgery to correct postural deformities and steroids to improve muscle strength. Translarna is designed to restore the production of dystrophin in muscles by making cells bypass the nonsense mutation when making the protein. The market for DMD treatments was projected ​ to grow from $3.42 billion in 2024 to $8.19 billion by 2029, with a growth of 19.13% per year. The growth is driven by the increasing DMD burden and rising investments in the space. Translarna itself bagged $355.8 million in net revenues in 2023 compared to $288.6 million in 2022. Other treatments on the market for various types of DMD include Sarepta’s AMONDYS 45™ (casimersen) and gene therapy Elevidys. Meanwhile, Pfizer’s gene therapy fordadistrogene movaparvovec hit a setback in a phase 3 trial when it failed to meet its primary efficacy endpoint. “DMD is a highly morbid, complex and rare disorder that will continue to be treated with a combination of therapies, including those that target inflammation (such as deflazacort or other corticosteroids) and genetic targeted therapies, such as Translarna in the case of DMD secondary to nonsense mutations,” Klein said. “Given disease heterogeneity it will be important for there to be multiple therapeutic options.”