Acid sphingomyelinase deficiency

Americans can’t afford their medications. About 25% leave prescriptions unfilled, split pills, or skip doses. Seniors face challenges covering non-Medicare services, including prescriptions. Even those with commercial health insurance are not immune. One-third of insured adults worry about affording their premiums, and 44% must meet increasingly high deductibles before insurance even kicks in. As a result, 41% of adults carry substantial medical debt. At the same time, FDA approvals for therapeutics targeting rare diseases are on the rise, including those for cancer, Alzheimer’s, and many previously untreatable diseases. In fact, 54% of 2022’s novel drug approvals targeted rare diseases. They encompass groundbreaking therapies like the first acid sphingomyelinase deficiency treatment, a prurigo nodularis remedy, and an obstructive hypertrophic cardiomyopathy therapy. In 2023, the first enzyme replacement therapy for non-neurological alpha-mannosidosis effects gained early approval. Breakthroughs, though welcome, are staggeringly expensive. In fact, Hemgenix, a new treatment for hemophilia, is officially the most expensive drug in the world at $3.5 million annually, followed by Zynteglo for thalassemia at $2.8 million per dose, and Zokinvy for Hutchinson-Gilford progeria syndrome at $1.7 million. Even medications for more common conditions can be cripplingly expensive. Over the past decade, median annual prices for disease-modifying therapies for multiple sclerosis have surged by nearly $34,000, reaching a median price of almost $94,000. Some have witnessed price hikes of over 200%, with nine now exceeding $100,000. Rheumatoid arthritis patients face medical costs that average $12,500 annually, and over $36,000 for those prescribed a biologic. Those biologic disease-modifying antirheumatic drugs range from $25,000–$40,000 a year. Leqvio, a semiannual cholesterol-lowering injection, costs between $3,191 and $6,782 per dose. In addition to financial challenges, patients with rare diseases encounter difficulties in accessing essential clinical services despite availability, and that combined with pressure from payers to lower care delivery costs has driven the rapid growth of ambulatory infusion centers. Ambulatory infusion centers are more accessible than hospitals because they are scattered geographically, unlike single-location hospitals in urban centers. Infusion center settings allow medical professionals to closely monitor patients, improving adherence for complex conditions requiring infusions. Research indicates a 79% adherence rate for office-based infusions, compared to 74% at hospitals and 64% at home. Home or hospital-infused patients averaged four to five specialist visits, while infusion center-infused patients averaged 14, leading to better disease management and outcomes. Administering specialty drugs through ambulatory infusion centers offers substantial cost savings. These settings can cut specialty medication administration expenses by 50% for major HCPS codes, which constitute a significant portion of specialty medical spending, reducing costs by $16,000 to $37,000 per privately insured patient annually for major conditions. Those dealing with rare, complex, and chronic conditions need a new care model to ensure that they have access to lifesaving, transformative medications regardless of their insurance coverage, or lack of it. Ambulatory infusion centers are increasingly providing that much-needed access, support and, increasingly, financial assistance. To offer a differentiated patient financial experience, some infusion centers have partnered with software companies to further enhance their service offerings. Such technology platforms utilize data and predictive analytics to flag patients in need and match them with relevant financial resources, including drug manufacturer copay assistance programs, foundation grants, government assistance, and more. These companies can streamline and automate what is often a manual, labor-intensive process, empowering staff to reach more patients and maximize cost-saving opportunities. By improving affordability, collaborations between ambulatory infusion centers and comprehensive software solution providers who automate financial navigation expand access to lifesaving drugs and increase the likelihood of treatment adherence and positive outcomes. Progress comes at a price. Developing new medications and treatments for rare diseases takes years of research and deep pockets, but the human costs for real patients and their families, healthcare providers, and caretakers must be factored in as well. Healthcare has traditionally been built around the convenience of the provider and not the patient. Worse, it tends to treat all patients the same regardless of the condition they are trying to manage. If we want to improve compliance, we have to make access, support, and most importantly financial assistance a priority.

Cancer drug research is producing more targeted therapies that address particular genetic signatures. Last year saw a fair share of new targeted cancer therapies, but 2022 was also notable for the expansion of genetic insights beyond oncology. Three gene therapies won FDA approval and the growing list of such therapies in clinical testing suggests the trend will continue this year. The three newly approved gene therapies are among the 42 drugs and biological products that won FDA nods in 2022. That total excludes imaging agents and diagnostic products, some of which are included in the FDA’s lists. Also excluded from the total are previously approved drugs that won additional approvals in new indications. The tally of new therapies approved in 2022 is less than the 60 new products approved in 2021, a year in which Covid-19 triggered a flood of research dollars that spread throughout the drug research sector and led to the first FDA-approved vaccines for the novel coronavirus. The first gene therapy to win the FDA’s nod in 2022 was Zynteglo, a Bluebird Bio treatment for the rare blood disorder beta thalassemia. The biotech company followed that regulatory decision with an approval for Skysona, a gene therapy for cerebral adrenoleukodystrophy, an ultra-rare neurodegenerative disorder. But gene therapy is expanding to conditions that while still rare, address patient populations measured in the tens of thousands rather than in the thousands. Hemophilia B is one such disorder. Approval of CSL Behring’s Hemgenix made that product the first gene therapy authorized for hemophilia B. The approval also set a record for the pricing of a therapy of any type. CSL is charging $3.5 million for its therapy, topping the prices of both Bluebird Bio products. Gene therapy offers the potential to address genetic drivers of a disease with a one-time treatment. Thus, the potentially curative effects of gene therapy come with premium pricing. However, it’s worth noting that all of these products come with value-based agreements that tie the payer reimbursement of the therapy to defined outcomes demonstrating patient benefit. Industry observers say that as gene therapies become more prevalent, such agreements will become more common. Meanwhile, more gene therapies are on the way. Regulatory decisions to watch in 2023 include a BioMarin Pharmaceutical gene therapy for hemophilia A and a Bluebird gene therapy for sickle cell disease. Moving on from gene therapy but staying within the realm of rare disease, 2022 saw several disorders receive their first-ever approved treatments. Sanofi drug Enjaymo and Agios Pharmaceuticals’ Pyrukynd are the first approved therapies for anemias caused by cold agglutinin disease and pyruvate kinase deficiency respectively. Acid sphingomyelinase deficiency, a rare disorder characterized by the lack of a key enzyme, now has its first FDA approved treatment: Sanofi’s Xenpozyme. The U.S. approval for Xenpozyme followed the approval of that product in Europe and Japan. In other metabolic drug news, Eli Lilly won the regulatory nod for Mounjaro, a type 2 diabetes drug projected to become a blockbuster seller. Possibly the most high-profile approval of 2022 was the decision for Relyvrio, the Amylyx Pharmaceuticals treatment for amyotrophic lateral sclerosis. Two FDA advisory committee meetings were held last year for the drug—unusual for a single product. Along the way, the biotech navigated uncertainty about whether another clinical trial was needed to support its regulatory submission. The FDA ultimately concluded it could review Relyvrio based on the results of one Phase 2 study. But in a surprising move, the agency granted the drug a standard approval rather than an accelerated one. Relyvrio’s September regulatory nod made it just the third drug approved to date for ALS. Cancer therapies are a sure bet to top annual lists of new FDA-approved products and 2022 saw its share of new oncology products. But compared to previous years, this past one was a relatively slow one for new cancer drugs. A total of 14 new cancer products passed regulatory muster. One of the most closely watched of those drugs was Mirati Therapeutics’ Krazati for non-small cell lung cancer. The small molecule targets a rare mutation called KRAS G12C, and the Mirati drug’s approval puts it in direct competition with Amgen’s Lumakras. Multiple myeloma is another type of cancer welcoming new products. Carvykti, a CAR-T therapy from Johnson & Johnson and Legend Biotech, is one of two multiple myeloma drug approvals for J&J this year. The agency also approved Tecvayli, a J&J antibody drug that goes after the same target as Carvykti. However, the subcutaneously injected formulation of Tecvayli is intended to offer patients a more convenient dosing option compared to intravenously infused cell therapies. J&J may soon add a fifth therapy to its lineup of multiple myeloma products. During the recent annual meeting of the American Society of Hematology, the pharmaceutical giant presented data supporting its application for talquetamab, which could become the first drug approved to address the novel cancer target GPRC5D. That will be one of the regulatory decisions to watch for in 2023.

Continued strong growth in Q3 with key regulatory milestones achieved Paris, October 28, 2022 Q3 2022 sales growth of 9.0% at CER driven by Specialty Care and Vaccines Specialty Care grew 19.9% driven by Dupixent® performance (€2,314 million, +44.5%) and launch momentum in Rare DiseaseVaccines up 23.5% from strong Flu sales in the quarter, rebound of Travel vaccines and growth of Meningitis and PPH franchisesGeneral Medicines achieved 2.4% core assets growth despite lower Lovenox® sales due to decreasing demand from COVID-19CHC up 1.9% with strong growth in Digestive Wellness and Cough & Cold in a normalizing market environment post-COVID-19 Q3 2022 business EPS(1) up 17.9% at CER driven by higher sales and margin expansion BOI margin up 1.9 ppt to 36.0% due to gross margin improvement from efficiency gains, product mix and EUROAPI deconsolidationBusiness EPS(1) of €2.88, up 32.1% on a reported basis and 17.9% at CERIFRS EPS of €1.66, down 9.8 %, reflecting a €1,586 billion impairment charge related to SAR444245 Progress on Corporate Social Responsibility strategy Access to Medicine Foundation recognized Sanofi Global Health Unit’s work to improve insulin access in low-middle income countries Key R&D milestones and regulatory achievements Dupixent® approved in the U.S. as the first and only treatment for adults with prurigo nodularisFDA granted priority review for Altuviiio™ (efanesoctocog alfa) for the treatment of hemophilia AFDA approved XenpozymeTM for the treatment of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patientsCHMP recommended approval of Beyfortus® (nirsevimab) for prevention of RSV disease in infants CHMP recommended approval of Enjaymo™ in adult patients with cold agglutinin disease (CAD) Full-year 2022 business EPS guidance revise upward Sanofi now expects 2022 business EPS(1) to grow approximately 16%(2) at CER, barring unforeseen major adverse events. Applying average October 2022 exchange rates, the positive currency impact on 2022 business EPS is estimated between +9.5% to +10.5% Sanofi Chief Executive Officer, Paul Hudson, commented: “Our strong results for the third quarter demonstrate that Sanofi is on the right path, with a remarkable performance of 20% growth in both Specialty Care and Vaccines, leading us to again raise our business EPS guidance for the full-year. Our commitment to breakthrough science is bearing fruit. Three of our priority first or best-in-class medicines reached important regulatory milestones. Beyfortus® was recommended by EMA’s CHMP for prevention of RSV disease in all infants while Altuviiio™ was granted priority review by the US FDA for people with hemophilia A. Dupixent® keeps breaking new ground with a recent US FDA approval making it the first and only treatment indicated for prurigo nodularis, the second indication in dermatology, and fifth overall for Dupixent in the US. Social impact continues to be at the center of our company’s agenda, as illustrated by the introduction of our first two carbon offsetting programs. Looking ahead, we are well positioned to achieve our BOI margin target of 30% in 2022 and to stay focused on our ambition to transform the practice of medicines for patients around the world.” Q3 2022 Change Change at CER 9M 2022 Change Change at CER IFRS net sales reported €12,482m +19.7% +9.0% €32,272m +16.2% +8.6% IFRS net income reported €2,076m -10.1% _ €5,260m +3.7% — IFRS EPS reported €1.66 -9.8% _ €4.20 +3.7% — Free cash flow(3) €2,695m +22.4% _ €5,937m +6.9% — Business operating income €4,498m +26.5% +13.0% €10,316m +22.0% +12.8% Business net income(1) €3,606m +31.8% +17.7% €8,200m +26.5% +16.9% Business EPS(1) €2.88 +32.1% +17.9% €6.55 +26.4% +17.0% Changes in net sales are expressed at constant exchange rates (CER) unless otherwise indicated (definition in Appendix 7). (1) In order to facilitate an understanding of operational performance, Sanofi comments on the business net income statement. Business net income is a non-GAAP financial measure (definition in Appendix 7). The consolidated income statement for Q3 2022 is provided in Appendix 3 and a reconciliation of reported IFRS net income to business net income is set forth in Appendix 4; (2) 2021 business EPS was €6.56; (3) Free cash flow is a non-GAAP financial measure (definition in Appendix 7). Attachment Access here the full press release