α-glucosidase

Sanofi has shared positive results for its enzyme replacement therapy, avalglucosidase alfa, across a wide range of Pompe disease patient groups. Affecting approximately one in every 40,000 people in the UK, Pompe disease is a rare genetic disorder caused by low levels of the enzyme acid alpha-glucosidase. This results in the build-up of glycogen in muscle cells throughout the body, leading to potentially irreversible damage to the heart and skeletal muscles. The disorder can present as either infantile-onset Pompe disease (IOPD), the most severe form of the disease with rapid onset in infancy, or late-onset Pompe disease (LOPD), which progressively damages the muscles over time. If left untreated, IOPD can lead to heart complications and death within the first year of life, while patients with LOPD may require ventilation to help with breathing or a wheelchair to assist with mobility as the disease progresses. According to data from the mid-stage Mini-COMET study long-term extension, presented at this year’s WORLDSymposium, avalglucosidase alfa was associated with meaningful improvements in ptosis, or drooping eyelid, in paediatric patients with IOPD over nearly three years. Ptosis impacts approximately 50% of IOPD patients and can cause vision loss and decreased quality of life, Sanofi outlined. Positive safety results from the phase 3 Baby-COMET trial, which has been evaluating avalglucosidase alfa in treatment-naïve IOPD patients, were also presented at the WORLDSymposium, as well as key findings surrounding the therapy’s use in LOPD. This included eight-year follow-up results from the phase 2/3 NEO-EXT study of avalglucosidase alfa in patients with LOPD and real-world findings from the international, voluntary Pompe Registry sponsored by Sanofi of those who switched to avalglucosidase alfa from prior treatment with a long-time standard of care, alglucosidase alfa. Alaa Hamed, global head of medical affairs, rare diseases, Sanofi, said: “The totality of data presented at WORLDSymposium builds upon existing evidence that supports the value of avalglucosidase alfa in treating Pompe disease, showcasing the therapy’s long-term durability and favourable efficacy and safety profile across a wide range of patient types and clinical circumstances…” Avalglucosidase alfa holds approvals to treat Pompe disease, with specific indications varying by country. In Europe, the therapy is marketed under the brand name Nexviadyme and approved for use in both LOPD and IOPD patients, while in the US, it is indicated for the treatment of LOPD in patients one year and older under the brand name Nexviazyme.

PRINCETON, N.J., Feb. 08, 2024 (GLOBE NEWSWIRE) -- Amicus Therapeutics, Inc. (Nasdaq: FOLD), today announced that WORLDSymposium™ has awarded Pombiliti™ (cipaglucosidase alfa-atga) + Opfolda™ (miglustat) the 2024 New Treatment Award, which recognizes important achievements in advancing treatments for lysosomal diseases which have attained regulatory approval. “We are honored that WORLDSymposium has recognized Pombiliti and Opfolda with the 2024 New Treatment Award,” said Bradley Campbell, President and Chief Executive Officer of Amicus Therapeutics, Inc. “It is a testament to more than a decade of dedication and commitment from Team Amicus along with dozens of families, physicians, researchers, and advocates around the world who worked tirelessly to see this medicine approved. Their partnership has been pivotal in continuing our promise to lead the fight in rare diseases, and we share this award with the entire global Pompe disease community.” Pombiliti + Opfolda is the first and only two-component therapy approved by the U.S. Food and Drug Administration (FDA) for adults with late-onset Pompe disease weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT). Pombiliti + Opfolda is a unique two-component therapy. Pombiliti is a recombinant human GAA enzyme (rhGAA) naturally expressed with high levels of bis-M6P (Mannose 6-Phosphate), designed for increased uptake into muscle cells. Once in the cell, Pombiliti can be properly processed into its most active and mature form to break down glycogen. Opfolda is an enzyme stabilizer designed to stabilize the enzyme in the blood. Late-onset Pompe disease is a rare, debilitating, and life-threatening lysosomal disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced levels of GAA lead to the accumulation of the substrate glycogen in the lysosomes of muscle cells and glycogen buildup causes muscle damage. Disease severity ranges across a spectrum, with predominant manifestations such as skeletal muscle weakness and progressive respiratory involvement. This is the second WORLDSymposium™ New Treatment Award presented to Amicus. Amicus received the award in 2017 for the first and only oral therapy approved for people living with Fabry disease. About Pombiliti + Opfolda Pombiliti + Opfolda, is a two-component therapy that consists of cipaglucosidase alfa-atga, a bis-M6P-enriched rhGAA that facilitates high-affinity uptake through the M6P receptor while retaining its capacity for processing into the most active form of the enzyme, and the oral enzyme stabilizer, miglustat, that’s designed to reduce loss of enzyme activity in the blood. U.S. INDICATIONSANDUSAGE POMBILITI in combination with OPFOLDA is indicated for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT). SAFETY INFORMATION HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS: Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, POMBILITI should be discontinued immediately and appropriate medical treatment should be initiated. INFUSION-ASSOCIATED REACTIONS (IARs): If severe IARs occur, immediately discontinue POMBILITI and initiate appropriate medical treatment. RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS: Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function, may be at risk of serious exacerbation of their cardiac or respiratory status during POMBILITI infusion. See PI for complete Boxed Warning. CONTRAINDICATION: POMBILITI in combination with Opfolda is contraindicated in pregnancy. EMBRYO-FETAL TOXICITY: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 60 days after the last dose. Adverse Reactions: Most common adverse reactions ≥ 5% are headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia. Please see full PRESCRIBING INFORMATION, including BOXED WARNING, for POMBILITI (cipaglucosidase alfa-atga) LINK and full PRESCRIBING INFORMATION for OPFOLDA (miglustat) LINK. About Amicus Therapeutics Amicus Therapeutics (Nasdaq: FOLD) is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a pipeline of cutting-edge, first- or best-in-class medicines for rare diseases. For more information please visit the company’s website at , and follow on Twitter and LinkedIn. PP-AT-ALL-0002-0224 CONTACTS: Investors: Amicus Therapeutics Andrew Faughnan Vice President, Investor Relations afaughnan@amicusrx.com (609) 662-3809 Media: Amicus Therapeutics Diana Moore Head of Global Corporate Affairs and Communications dmoore@amicusrx.com (609) 662-5079 FOLD–G

Sanofi is walking away from a deal to license an experimental Maze Therapeutics drug for a rare enzyme deficiency after the Federal Trade Commission challenged the transaction as anti-competitive. The French pharmaceutical giant already markets Lumizyme and Nexviazyme for the disorder, called Pompe disease. Until this year, they were the only available Pompe treatments. In an administrative complaint filed Monday, the anti-trust regulator said Sanofi’s deal for Maze’s drug candidate amounts to a large company trying to eliminate a smaller competitor. Both Sanofi and Maze disagree with the FTC’s position. South San Francisco-based Maze said it is reviewing its legal and business options. Sanofi isn’t waiting. The pharma giant said the FTC action will be a delay and it concluded contesting it would not be in the best interest of patients. Consequently, Sanofi will terminate the licensing agreement. Pompe is caused by mutations to the gene that codes for acid alpha glucosidase (GAA), an enzyme needed for breaking down glycogen in muscles. As a result, glycogen, a form of glucose, accumulates in skeletal, lung, and cardiac muscle tissue. Glycogen buildup leads to progressively worsening muscle weakness and respiratory problems that become fatal. Like many inherited enzyme deficiencies, treatment for Pompe is enzyme replacement therapy. Sanofi’s Lumizyme (marketed in Europe as Myozyme) was the first Pompe product, offering patients an engineered version of GAA. The annual cost of treatment is more than $750,000. Sanofi’s Nexviazyme (Nexviadyme in Europe) is also an engineered version of GAA, but designed in a way to improve the enzyme’s ability to clear glycogen. Nexviazyme was approved by the FDA in 2021 and by the European Commission last year. Maze drug candidate MZE001 takes a different approach to Pompe. Rather than replacing GAA, the Maze drug aims to impede glycogen production. MZE001 blocks glycogen synthase, an enzyme important in making glycogen. The drug is a small molecule that would be less expensive to manufacture than Sanofi’s engineered enzymes. It’s also formulated as a twice-daily pill that is much more convenient for patients than receiving regular infusions. When the licensing agreement for MZE001 was announced in May—$150 million up front and up to $600 million in milestone payments—Maze had encouraging Phase 1 data showing the drug was well tolerated and it also led reduction in glycogen levels across all of the tested doses. Both Sanofi and Maze said the deal placed the small molecules in the hands of a global company with the resources and Pompe experience to advance its development. The FTC disagrees. “This is a case about a monopolist seeking to eliminate a nascent threat to its monopoly,” the agency said in the complaint. Many key details of the 17-page complaint are redacted, but the publicly viewable portions portray a pharmaceutical giant concluding its own products would not be competitive with the oral dose formulation of the Maze drug candidate. They also suggest that the licensing agreement was intended to keep the molecule from getting in the hands of rival pharma companies. The complaint goes on to state that by eliminating the competitive threat of MZE001, the deal contributes to Sanofi’s monopoly in Pompe, violating the anti-monopoly provisions of Section 2 of the Sherman Act. Revenue for the Sanofi Pompe franchise increased 7.3% year over year topping €1 billion in 2022, according to the company’s annual report. Sanofi attributes that growth to Nexviazyme’s launch in U.S., Europe, and Japan. However, 2022 sales of Lumizyme/Myozyme are from the prior year due to eligible Pompe patients switching to Nexviazyme. Pompe patients do have a new treatment option available from Amicus Therapeutics. In September, the FDA approved Amicus’s Pombiliti, an engineered version of GAA. That therapy is taken with Opfolda, a small molecule that Amicus designed to improves muscle cell uptake of Pombiliti. But the new Amicus products are not direct competitors to Sanofi’s Pompe therapies. The FDA’s approval o the combination therapy covers the treatment of Pompe patients who are not improving with the Sanofi therapies. The FTC complaint notes that Amicus’s therapy currently has little to no market share, posing little price competition to the Sanofi products. “Because Amicus Therapeutics’ two-component [enzyme replacement therapy] was only approved as a second-line therapy (for patients not improving on Sanofi’s therapies), Sanofi has little to no incentive to decrease its list prices or offer significant discounts or rebates on Lumizyme and Nexviazyme, which remain the only FDA-approved treatments for newly diagnosed patients starting treatment for Pompe disease,” the FTC said. The regulator set a May 15, 2024 date for an evidentiary hearing—a little more than one year after Sanofi and Maze announced the licensing agreement. Sanofi’s assertion that protracted litigation will not help Pompe patients has some merit. The Maze molecule has been ready for Phase 2 testing and further clinical development is in limbo as long as the case is ongoing. With Sanofi bowing out of development of MZE001, privately held Maze will need to figure out how to finance development of that molecule and others in its pipeline. The initial deal called for Sanofi to pay Maze $130 million up front and make a $20 million equity investment in the biotech when it completes an initial public offering, the FTC complaint revealed. Regardless of whether Sanofi invests in Maze or not, the market remains mostly closed for biotech IPOs.