Papillary thyroid cancer

First marketing authorization submission for sepiapterin with additional global submissions to follow in 2024 SOUTH PLAINFIELD, N.J., March 28, 2024 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) announced today the submission of the sepiapterin MAA to the European Medicines Agency. The MAA submission is for the treatment of pediatric and adult patients with PKU, including the full spectrum of disease subtypes. "This MAA submission is the first in a series of global submissions for sepiapterin as we move closer to bringing this therapy to children and adults with PKU worldwide," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "The strength of the sepiapterin data generated in clinical trials substantiate how differentiated sepiapterin is from currently available therapies and support how sepiapterin could address the significant unmet medical need for PKU patients." The sepiapterin MAA includes the results of the phase 3 APHENITY trial in which sepiapterin had a statistically significant and clinically meaningful reduction in blood phenylalanine levels in pediatric and adult PKU patients. Sepiapterin treatment resulted in a mean reduction in Phe levels of 63% in the overall treated population and 69% in the subgroup of subjects with classical PKU. The vast majority of subjects (84%) achieved Phe control in accordance with treatment guidelines, and 22% of subjects had normalization of Phe levels. Data from the ongoing APHENITY open-label extension study demonstrates that these sepiapterin treatment effects are durable. In addition, data from the Phe tolerance sub study demonstrate that subjects are liberalizing their diet, beyond the recommended daily allowance of protein, and maintaining control of Phe within target levels from guidelines. The ability to enable patients to liberalize their highly restrictive diets and still maintain Phe control, is a very meaningful sepiapterin treatment benefit for physicians, payers and patients. PTC expects to submit the sepiapterin NDA to the FDA no later than the third quarter of 2024. Submissions in 2024 are planned in a number of additional key countries where PTC has existing rare disease commercial infrastructure including Brazil and Japan. About Sepiapterin Sepiapterin (formerly PTC923) is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, which is a critical enzymatic cofactor involved in the metabolism and synthesis of numerous metabolic products. Sepiapterin is a more bioavailable precursor than exogenously administered synthetic BH4 and has the potential to treat the broad range of PKU patients. About Phenylketonuria Phenylketonuria (PKU) is a rare, inherited metabolic disease, which affects the brain.1 It is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine.1 If left untreated or poorly managed, phenylalanine – an essential amino acid found in all proteins and most foods – can build up to harmful levels in the body. This causes severe and irreversible disabilities, such as permanent intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems.1 Newborns with phenylketonuria initially don't have any symptoms, but symptoms are usually progressive, and damage caused by toxic levels of phenylalanine in the first few years of life is irreversible.2,3 Diagnosis of phenylketonuria usually takes place during newborn screening programs.4 There are an estimated 58,000 people with phenylketonuria globally. 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 patients with rare disorders. PTC's ability to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC's mission is to provide access to best-in-class treatments for patients who have little to no treatment options. PTC's strategy is to leverage its strong scientific and clinical expertise and global commercial infrastructure to bring therapies to patients. PTC believes this allows it to maximize value for all its stakeholders. To learn more about PTC, please visit us at and follow us on Facebook, Instagram, LinkedIn and Twitter at @PTCBio. For More Information: Investors: Kylie O'Keefe +1 (908) 300-0691 kokeefe@ptcbio.com Media: Jeanine Clemente +1 (908) 912-9406 jclemente@ptcbio.com Forward-Looking Statement: 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 statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of 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; 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; 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; 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 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. Acronyms: EMA: European Medicines Agency FDA: U.S. Food and Drug Administration MAA: Marketing Authorization Application NDA: New Drug Application PKU: Phenylketonuria View original content: SOURCE PTC Therapeutics, Inc. Company Codes: NASDAQ-NMS:PTCT

Duchenne muscular dystrophy has several approved drugs, including a gene therapy that provides children who have the rare, inherited muscle-wasting disease the option of a one-time treatment. But each of these therapies only treats certain defined patient groups. While corticosteroids can reach more Duchenne patients, they introduce many side effects. The FDA just approved the first nonsteroidal Duchenne drug. The late Thursday approval of Italfarmaco drug givinostat covers patients age 6 and older and spans all genetic variants that drive the inherited disease. The twice-daily oral suspension company will be marketed under the brand name Duvyzat. In an email, Italfarmaco said Duzyvat’s price has not yet been set. The Milan, Italy-based company expects the product will become available in the third quarter of this year. In Duchenne, a genetic mutation leads to insufficient amounts of a key muscle protein called dystrophin. The disorder almost exclusively affects boys, showing its first signs when patients are between ages of 2 and 5. Progressively worsening muscle function robs patients of the ability to walk. The disease’s muscle weakening effects eventually reach the heart and lungs, typically leading to death when patients are in their 20s, though some live into their 30s. Though Duchenne is rare, it is the most common type of muscular dystrophy. Privately held Italfarmaco discovered Duvyzat in partnership with the Telethon and Duchenne Parent Project in Italy. The drug is a small molecule designed to block an enzyme called histone deacetylase, or HDAC. While the precise way that this approach helps is not known, Italfarmaco has pointed to research showing that Duchenne patients have high HDAC activity. By blocking it, the drug is intended to inhibit excessive pathological activity associated with the enzyme. The FDA’s approval of Duvyzat is based on the results of a placebo-controlled Phase 3 clinical trial enrolling 179 patients. The main goal of the 18-month study was to show a change in muscle function as measured by a stair-climbing test. Steroids are a standard first-line treatment for Duchenne and all study participants continued to receive these drugs during the clinical trial. According to the results, patients in the study drug arm demonstrated statistically significant lower decline in the ability to climb four stairs compared to those in the placebo group. A secondary goal was measuring the change in physical function as scored according to a commonly used rating scale to measure motor function in Duchenne patients who can still walk. The FDA said patients treated with Duvyzat showed less worsening in scores at 18 months compared to those in the placebo arm. The most common side effects reported in the trial include diarrhea; abdominal pain; nausea and vomiting; a decrease in platelets; an increase in triglycerides, a type of body fat; and fever. Italfarmaco said the side effects were all mild to moderate. Duvyzat’s label advises physicians to monitor platelet counts and triglyceride levels. The dose may be adjusted to manage those side effects as well as moderate-to-severe diarrhea. The label also notes the drug may increase the risk of an irregular heartbeat. Full trial results were published online this week in The Lancet Neurology. Corticosteroids have been used off-label for years as a Duchenne treatment. PTC Therapeutics’ Emflaza was approved for Duchenne in 2017, making it the first steroid approved specifically for Duchenne. This pill may be used by patients ages 2 to 5. Last October, FDA approval of Santhera’s oral suspension Agamree introduced another steroid option for patients age 2 and older. Adverse effects associated with the steroids used to treat Duchenne include weight gain, behavioral issues, gastrointestinal problems, and weakening of bones. Sarepta and NS Pharma have commercialized Duchenne drugs, each one addressing specific genetic mutations that drive the disease. Elevidys, a Sarepta gene therapy, won accelerated approval last year for treating all Duchenne patients but only those ages 4 and 5. Expansion of the approval to other age groups faces a tall hurdle. In a confirmatory Phase 3 study, Elevidys fell short of achieving statistical significance on the trial’s main goal. Nevertheless, Sarepta points to statistical significance according to the trial’s secondary goals. A regulatory submission for Duvyzat is currently under review in Europe. Italfarmaco said it is also discussing the drug with regulatory agencies in other parts of the world. The company will commercialize Duvyzat through a newly established U.S. subsidiary, ITF Therapeutics. “Duchenne muscular dystrophy is a disease with significant unmet medical need and Duvyzat has the potential to benefit a broad DMD patient population independent of the underlying gene mutation that causes the disease,” Francesco De Santis, president of Italfarmaco Holding and chairman of Italfarmaco Group, said in a prepared statement. “The FDA approval highlights the dedication of Italfarmaco’s research and clinical teams to achieve this milestone for the company.”

With an approval in hand, Italfarmaco’s next goal is to get Duvyzat to U.S. patients “as quickly as possible,” according to the company’s chief medical officer Paolo Bettica, M.D., Ph.D. At a watershed moment for Duchenne muscular dystrophy (DMD) treatment, privately held Italian drugmaker Italfarmaco has added a new therapeutic option to the armamentarium against the debilitating muscle-wasting disorder. Late Thursday, the U.S. FDA gave a thumbs-up to Italfarmaco’s histone deacetylase (HDAC) inhibitor Duvyzat, also known as givinostat. The approval makes the product the first nonsteroidal drug approved to treat patients with all genetic variants of DMD in the U.S., the FDA said in an approval announcement. Duvyzat, which is taken orally, is specifically cleared to treat DMD in patients ages 6 and older, Italfarmaco said in a separate release. DMD, which is the most common form of muscular dystrophy around the world, is a severe neuromuscular genetic disease marked by progressive muscle weakness and degeneration. The disease is caused by mutations in the dystrophin gene that lead to an absence of functional dystrophin proteins, in turn leaving muscle fibers prone to injury, inflammation and impaired regeneration and replacement. DMD primarily affects boys, but girls can be carriers of the disease, according to the Muscular Dystrophy Association. Boasting a unique mechanism of action, Duvyzat works by modulating the deregulated activity of HDACs in the dystrophic muscle, which Italfarmaco says is a major consequence of the dystrophin deficit associated with DMD. By inhibiting HDAC overactivity, Duvyzat is designed to address the cascade of events leading to muscle damage, ultimately slowing down muscle deterioration, Italfarmaco said. Citing the “tremendous unmet need” for DMD therapies that can help a broad range of patients, Craig McDonald, M.D., an investigator on Duvyzat’s pivotal phase 3 trial, said in a statement that Italfarmaco’s drug has the potential to become a “key component of the standard of care for people living with DMD.” The FDA based its approval on results from Italfarmaco’s phase 3 EPIDYS trial, which looked at 179 boys ages 6 and up who received either Duvyzat twice daily or placebo in addition to glucocorticosteroid treatment. At the trial’s 18-month mark, patients on Duvyzat showed significantly less decline in the time it took to complete a four-stair climb measure of muscle function. With an approval in hand, Italfarmaco’s next goal is to get Duvyzat to U.S. patients “as quickly as possible,” according to the company’s chief medical officer Paolo Bettica, M.D., Ph.D. To that end, the company has “significantly expanded its U.S. presence” with the launch of subsidiary ITF Therapeutics, which will handle marketing for the drug in the States. Italfarmaco said Thursday that ITF is working closely with healthcare providers, patient advocacy groups and payers to help get Duvyzat on pharmacy shelves. Privately held Italfarmaco was established in 1938 and currently operates in Italy and abroad from its headquarters in Milan. The company mainly makes drugs for cardiovascular, immuno-oncologic and gynecological disorders, according to its website. With its Duvyzat green light, Italfarmaco will now have to go up against the likes of Sarepta Therapeutics, which boasts a suite of exon-skipping therapies for DMD such as Exondys 51, Vyondys and Amondys. Meanwhile, Sarepta made a splash last summer with the FDA approval of its DMD gene therapy Elevidys, which has become one of the world’s most expensive drugs with a price tag of $3.2 million. Elevidys works by delivering a micro-dystrophin-encoding gene into a patient’s muscle tissue to prompt production of the micro-dystrophin protein. As Sarepta waits on a potential label expansion for Elevidys, the company said in late February that it’s seen early success with the gene therapy’s launch. The drug brought home total sales of $200.4 million last year, with $131.3 million coming in 2023’s fourth quarter. Elsewhere, Santhera Pharmaceuticals and Catalyst Pharmaceuticals in October received an FDA nod for their own DMD therapy—a dissociative steroid known as Agamree, or vamorolone. And, just this week, PTC Therapeutics revealed plans to resubmit its application for the nonsense mutation DMD candidate Translarna to the FDA by the middle of the year. The move comes after the U.S. regulator snubbed PTC’s drug in 2016 and 2017.