Paris, February 24, 2023. Today, at WORLDSymposiumTM, data from the Phase 3 COMET study long-term extension showed sustained treatment effect of Nexviazyme® (avalglucosidase alfa-ngpt) over nearly three years in late-onset Pompe disease (LOPD) patients who were treatment-naïve as well as those who switched from long-time standard of care, alglucosidase alfa, during the 96-week extension period. Additionally, a separate analysis of respiratory function showed clinical benefit over two years for patients who switched to Nexviazyme regardless of prior response to alglucosidase alfa.
Priya S. Kishnani, MD
C.L. and Su Chen Professor of Pediatrics; Medical Director, YT and Alice Chen Pediatrics Genetics and Genomics Center; and Division Chief, Medical Genetics, Duke University Medical Center
“The results presented at the 2023 WORLDSymposium continue to build on the data from the clinical trials on the value and long-term impact Nexviazyme may provide for a wide variety of people living with late-onset Pompe disease, from newly diagnosed patients to those who have been previously treated with alglucosidase alfa. Further, when examining patients treated with Nexviazyme who switched from using alglucosidase alfa, these data show clinical benefit both for patients who were stable on alglucosidase alfa and those who experienced sub-optimal response or decline.”
Bill Sibold
Global Head of Specialty Care, Sanofi
“These long-term data over nearly three years add to the robust body of evidence that consistently shows the clinical benefit and durability of effect of treatment with Nexviazyme for both treatment-experienced and treatment-naïve people living with late-onset Pompe disease. We continue to learn from our 20 years of experience in Pompe disease and build on our findings in an effort to advance the standard of care.”
Nexviazyme is a monotherapy approved in the US and other markets for the treatment of LOPD. It is also approved for infantile-onset Pompe disease (IOPD) in certain markets outside of the US.
Nexviazyme maintained treatment effect at 145 weeks
The Phase 3 COMET trial enrolled 100 previously untreated LOPD patients who were randomized to receive either Nexviazyme (20 mg/kg) or alglucosidase alfa (20 mg/kg) every two weeks for 49 weeks during the double-blind primary analysis period. During the open-label extension period, long-term efficacy and safety outcomes were assessed up to 145 weeks in patients who continued their treatment with Nexviazyme (n=51), as well as those who switched to treatment with Nexviazyme from alglucosidase alfa (n=44) at the conclusion of the primary analysis period (Week 49).
After nearly three years (145 weeks), changes from baseline (least squares mean [standard error]) showed:
- Patients who received continuous Nexviazyme treatment for 145 weeks experienced sustained improvements in respiratory and motor function, showing a 1.40 (1.21) point improvement in forced vital capacity (FVC) percent-predicted and an average increase of 20.65 (9.60) meters in walking distance as measured by the six-minute walk test (6MWT), respectively, compared to baseline.
- Patients who switched from alglucosidase alfa to Nexviazyme treatment during the extension period experienced stabilization of treatment effect, showing a 1.18 (1.32) point improvement in FVC percent-predicted and an average increase of 0.29 (10.42) meters in walking distance (6MWT), compared to baseline.
The safety profile during treatment with Nexviazyme was comparable between both study groups (those who started Nexviazyme in the primary analysis period and those who switched to Nexviazyme during the extension period). No new safety signals were observed in patients who switched from alglucosidase alfa to Nexviazyme during the extension period. Across both Nexviazyme treatment groups, five patients discontinued treatment during the extension period due to six adverse events (AEs); four were treatment-related (ocular hyperemia, erythema, urticaria, respiratory distress), and two were non-treatment-related (acute myocardial infarction, pancreatic adenocarcinoma).
Clinical benefits seen over two years for patients who switched to Nexviazyme
Subgroup analyses were also performed to assess respiratory function outcomes for the 44 patients who switched to Nexviazyme in the long-term extension period of the Phase 3 COMET study. Patients were divided into two subgroups, responders (n=14) and non-responders (n=30) based on individual responses to initial treatment with alglucosidase alfa, as measured by the change in FVC percent-predicted (ΔFVC %predicted/year) pre- (baseline-week 49) and post-switch (week 49-week 145). Findings showed clinical benefits over two years following switch to Nexviazyme regardless of prior response to alglucosidase alfa:
- Patients who responded to alglucosidase alfa treatment in the primary analysis period had increased respiratory function (ΔFVC slope, 4.67±1.28%/yr, p<0.001), which was maintained throughout the extension period with Nexviazyme treatment (ΔFVC slope, 0.14±0.94%/yr, p=0.88).
- Patients who did not respond to alglucosidase alfa treatment in the primary analysis period had reduced respiratory function while taking alglucosidase alfa (ΔFVC slope, ‑2.12±0.87%/yr, p=0.016); however, switching to Nexviazyme halted this decline in the extension period (ΔFVC slope, 0.15±0.61%/yr, p=0.81).
About Pompe disease
People living with Pompe disease have low levels of the enzyme acid alpha-glucosidase (GAA), which results in build-up of glycogen in muscle cells throughout the body, leading to irreversible damage to skeletal and cardiac muscles.
Pompe disease can present as 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 muscles over time. If left untreated, IOPD can lead to heart failure and death within the first year of life, while people living with LOPD may require mechanical ventilation to help with breathing or a wheelchair to assist with mobility as the disease progresses.
About Nexviazyme (avalglucosidase alfa-ngpt)
Nexviazyme (avalglucosidase alfa-ngpt) is an enzyme replacement therapy (ERT) designed to target the mannose-6-phosphate (M6P) receptor, the key pathway for uptake and transport of ERT. Nexviazyme aims to help improve uptake and enhance glycogen clearance in target tissues with an average 15-fold higher level of M6P moieties as compared to alglucosidase alfa, the comparator therapy in the pivotal study. Nexviazyme is approved in multiple markets around the world for the treatment of people living with Pompe disease, including the United States, the European Union, Japan, Canada, Switzerland, Australia, Brazil, Argentina, Taiwan, the United Arab Emirates, South Korea and the United Kingdom, with specific indications varying by country. In Europe, the medicine is marketed under the brand name Nexviadyme.
INDICATION
NEXVIAZYME (avalglucosidase alfa-ngpt) is used for the treatment of patients 1 year of age and older with late-onset Pompe disease [lysosomal acid alpha-glucosidase (GAA) deficiency].
IMPORTANT SAFETY INFORMATION
WARNING: SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS
Hypersensitivity Reactions Including Anaphylaxis
If you are taking NEXVIAZYME, you should know that severe and potentially life threatening allergic-type reactions known as anaphylaxis and severe hypersensitivity reactions have occurred during and after NEXVIAZYME treatment. You should seek immediate medical care if signs and symptoms of anaphylaxis or hypersensitivity reactions occur. If such a reaction is severe enough, your doctor may decide to immediately discontinue the infusion and provide immediate medical care. Appropriate medical support measures may be administered during your infusion, and you may require close observation during and after NEXVIAZYME administration.
Infusion-Associated Reactions (IARs)
If you are taking NEXVIAZYME, you should know that severe IARs have occurred during and after NEXVIAZYME treatment. If severe IARs occur during your NEXVIAZYME infusion, your doctor may decide to immediately discontinue the infusion and provide appropriate medical care. If you have an acute underlying illness at the time of NEXVIAZYME infusion you may be at greater risk for IARs. If you have advanced Pompe disease you may have compromised heart and breathing function, which may put you at a higher risk of severe complications from IARs.
Risk of Acute Cardiorespiratory Failure in Susceptible Patients
If you are likely to develop fluid volume overload, or have acute underlying breathing problems or compromised heart or breathing function that may require fluid restriction, there may be a risk of worsening of your heart or breathing status during NEXVIAZYME infusion. Your doctor may decide that close observation during NEXVIAZYME administration may be necessary.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis: See Boxed WARNING. Your doctor may decide to give you antihistamine, anti-fever and/or steroid medications before your infusions. Your doctor should consider the risks and benefits of restarting the infusion if you have a severe hypersensitivity reaction (including anaphylaxis) to NEXVIAZYME. If a mild or moderate hypersensitivity reaction occurs, your healthcare provider may slow the infusion rate or temporarily stop the infusion.
Infusion-Associated Reactions (IARs): See Boxed WARNING. Your doctor may decide to give you medications before your infusions to decrease the risk of IARs; however, IARs may still occur after receiving these medications. If mild or moderate IARs occur, your healthcare provider should consider decreasing the infusion rate or temporarily stopping the infusion which may help improve the symptoms.
Risk of Acute Cardiorespiratory Failure in Susceptible Patients: See Boxed WARNING.
ADVERSE REACTIONS
The most common adverse reactions (>5%) were headache, fatigue, diarrhea, nausea, joint pain, dizziness, muscle pain, itching, vomiting, shortness of breath, rash, “pins-and-needles” sensation, and hives.
Please see full Prescribing Information for complete details, including Boxed WARNING.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
Media Relations
Sandrine Guendoul | + 33 6 25 09 14 25 | sandrine.guendoul@sanofi.com
Kate Conway | + 1 508 364 4931 | kate.conway@sanofi.com
Investor Relations
Eva Schaefer-Jansen | + 33 7 86 80 56 39 | eva.schaefer-jansen@sanofi.com
Arnaud Delépine | + 33 6 73 69 36 93 | arnaud.delepine@sanofi.com
Corentine Driancourt | + 33 6 40 56 92 21 | corentine.driancourt@sanofi.com
Felix Lauscher | + 1 908 612 7239 | felix.lauscher@sanofi.com
Tarik Elgoutni| + 1 617 710 3587 | tarik.elgoutni@sanofi.com
Nathalie Pham | + 33 7 85 93 30 17 | nathalie.pham@sanofi.com
Sanofi Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions, and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the fact that product candidates if approved may not be commercially successful, the future approval and commercial success of therapeutic alternatives, Sanofi’s ability to benefit from external growth opportunities, to complete related transactions and/or obtain regulatory clearances, risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, trends in exchange rates and prevailing interest rates, volatile economic and market conditions, cost containment initiatives and subsequent changes thereto, and the impact that COVID-19 will have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. Any material effect of COVID-19 on any of the foregoing could also adversely impact us. This situation is changing rapidly, and additional impacts may arise of which we are not currently aware and may exacerbate other previously identified risks. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2022. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.