The goal of this observational study is to learn the effects of the drug velmanase alfa (Lamzede®) in the bodies of children under the age of 3 with Alpha-Mannosidosis.
The main questions it aims to answer are:
* study the effect of velmanase alfa on a marker of the disease called GlcNAc(Man)2 after one year of therapy
* explore how the child's body reacts to velmanase alfa during the therapy The parents or legal guardians of participants will be asked to provide the results of analyses performed in the routine clinical setting related to the participant's general health and the administration of velmanase alfa.
Additional data will be extracted from other observational sponsored studies/registries, compassionate use programs, investigator-initiated studies (IIS), and published case reports (presented in the literature) if existing.

Start Date01 Dec 2024

Sponsor / Collaborator

CHIESI Farmaceutici SpA

NCT04031066 / WithdrawnPhase 3

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis

Randomized, double-blind, placebo-controlled, parallel group study where subjects will receive velmanase alfa or placebo for 24 weeks.
Each subject undergoes to 8 complete visits at the clinic for clinical, laboratory and functional assessments. Study treatment is administered weekly through i.v. infusions

Start Date11 Jan 2021

Sponsor / Collaborator

CHIESI Farmaceutici SpA

NCT02998879 / CompletedPhase 2

A 24-month Multicenter, Open-label Phase II Trial Investigating the Safety and Efficacy of Repeated Velmanase Alfa (Recombinant Human Alpha-mannosidase) Treatment in Pediatric Patients Below 6 Years of Age With Alpha-Mannosidosis

The main objectives of the study are to evaluate safety and efficacy of repeated treatment with recombinant human alfa-mannosidase of patients with alfa-mannosidosis aged less than 6 years

Start Date01 Dec 2016

Sponsor / Collaborator

CHIESI Farmaceutici SpA

[+1]

100 Clinical Results associated with Velmanase alfa-tycv

100 Translational Medicine associated with Velmanase alfa-tycv

100 Patents (Medical) associated with Velmanase alfa-tycv

Literatures (Medical) associated with Velmanase alfa-tycv

01 May 2024·Molecular genetics and metabolism

Diagnosis of alpha-Mannosidosis: Practical approaches to reducing diagnostic delays in this ultra-rare disease

Review

Author: Cefalo, Graziella ; Santoro, Lucia ; Canalini, Fabrizio ; Rossi, Silvia ; Scarpa, Maurizio

Alpha-mannosidosis is an ultra-rare lysosomal disease that is caused by variants of the MAN2B1 gene on chromosome 19p13. These variants result in faulty or absent alpha-mannosidase in lysosomes, which leads to intracellular accumulation of mannose-containing oligosaccharides. Diagnosis of alpha-mannosidosis is often delayed, in part because of the rarity of the disease, its gradual onset and heterogeneity of presentation, but also because of the similarity of many signs and symptoms of the disease to those of other lysosomal diseases. Treatment of alpha-mannosidosis was previously limited to hematopoietic stem cell transplantation, but outcomes are variable and not all patients are eligible or have a suitable donor. Recently, an enzyme replacement therapy, recombinant human alpha-mannosidase (velmanase alfa), was approved for the treatment of non-neurological manifestations in adult and pediatric patients with alpha-mannosidosis. Treatment with velmanase alfa reduces serum levels of oligosaccharides, increases levels of immunoglobulin G, and improves patients' functional capacity and quality of life, although it is not effective for the neurologic phenotype because it does not cross the blood-brain barrier. Since the effects of velmanase alfa are more marked in children than adults, early diagnosis to allow early initiation of treatment has become more important. To support this, patient, parent/caregiver, and clinician awareness and education is imperative. A number of approaches can be taken to meet this goal, such as the development of disease registries, validated diagnostic algorithms, and screening tools, improved under-/post-graduate clinician education, easily accessible and reliable information for patients/families (such as that made available on the internet), and the formation of patient advocacy groups. Such approaches may raise awareness of alpha-mannosidosis, reduce the diagnostic delay and thus improve the lives of those affected.

20 Jul 2023·Orphanet journal of rare diseases

Exploring the feasibility of using the ICER Evidence Rating Matrix for Comparative Clinical Effectiveness in assessing treatment benefit and certainty in the clinical evidence on orphan therapies for paediatric indications.

Article

Author: Szkultecka-Debek, Monika ; Zibelnik, Natasa ; Drozd, Mariola ; King, Sarah ; Wex, Jaro

BACKGROUND:

The evaluation of clinical evidence takes account of health benefit (efficacy and safety) and the degree of certainty in the estimate of benefit. In orphan indications practical and ethical challenges in conducting clinical trials, particularly in paediatric patients, often limit the available evidence, rendering structured evaluation challenging. While acknowledging the paucity of evidence, regulators and reimbursement authorities compare the efficacy and safety of alternative treatments for a given indication, often in the context of the benefits of other treatments for similar or different conditions. This study explores the feasibility of using the Institute for Clinical and Economic Review (ICER) Evidence Rating Matrix for Comparative Clinical Effectiveness in structured assessment of both the magnitude of clinical benefit (net health benefit, NHB) and the certainty of the effect estimate in a sample of orphan therapies for paediatric indications.

RESULTS:

Eleven systemic therapies with European Medicines Agency (EMA) orphan medicinal product designation, licensed for 16 paediatric indications between January 2017 and March 2020 were identified using OrphaNet and EMA databases and were selected for evaluation with the ICER Evidence Rating Matrix: burosumab; cannabidiol; cerliponase alfa; chenodeoxycholic acid (CDCA); dinutuximab beta; glibenclamide; metreleptin; nusinersen; tisagenlecleucel; velmanase alfa; and vestronidase alfa. EMA European Public Assessment Reports, PubMed, EMBASE, the Cochrane Library, Clinical Key, and conference presentations from January 2016 to April 2021 were searched for evidence on efficacy and safety. Two of the identified therapies were graded as "substantial" NHB: dinutuximab beta (neuroblastoma maintenance) and nusinersen (Type I SMA), and one as "comparable" NHB (CDCA). The NHB grade of the remaining therapies fell between "comparable" and "substantial". No therapies were graded as having negative NHB. The certainty of the estimate ranged from "high" (dinutuximab beta in neuroblastoma maintenance) to "low" (CDCA, metreleptin and vestronidase alfa). The certainty of the other therapies was graded between "low" and "high". The ICER Evidence Rating Matrix overall rating "A" (the highest) was given to two therapies, "B+" to 6 therapies, "C+" to five therapies, and "I" (the lowest) to three therapies. The scores varied between rating authors with mean agreement over all indications of 71.9% for NHB, 56.3% for certainty and 68.8% for the overall rating.

CONCLUSIONS:

Using the ICER Matrix to grade orphan therapies according to their treatment benefit and certainty is feasible. However, the assessment involves subjective judgements based on heterogenous evidence. Tools such as the ICER Matrix might aid decision makers to evaluate treatment benefit and its certainty when comparing therapies across indications.

01 Jul 2023·Journal of inherited metabolic disease

Long‐term safety and efficacy of velmanase alfa treatment in children under 6 years of age with alpha‐mannosidosis: A phase 2, open label, multicenter study

Article

Author: Guffon, Nathalie ; Zardi, Giulia ; Muschol, Nicole ; Ballabeni, Andrea ; Hennermann, Julia B. ; Tummolo, Albina ; Bruno, Irene ; Konstantopoulou, Vassiliki ; Lund, Allan ; Ceravolo, Ferdinando

Abstract:

Alpha‐mannosidosis (AM) is a rare, autosomal recessive, lysosomal storage disorder caused by alpha‐mannosidase deficiency that leads to the accumulation of mannose‐rich oligosaccharides. AM symptoms and severity vary among individuals; consequently, AM is often not diagnosed until late childhood. Velmanase alfa (VA), a recombinant human lysosomal alpha‐mannosidase product, is the first enzyme replacement therapy indicated to treat non‐neurological symptoms of AM in Europe. Previous studies suggested that early VA treatment in children may produce greater clinical benefit over the disease course than starting treatment in adolescents or adults; however, long‐term studies in children are limited, and very few studies include children under 6 years of age. The present phase 2, multicenter, open‐label study evaluated the safety and efficacy of long‐term VA treatment in children under 6 years of age with AM. Five children (three males) received VA weekly for ≥24 months, and all children completed the study. Four children experienced adverse drug reactions (16 events) and two experienced infusion‐related reactions (12 events). Most (99.5%) adverse events were mild or moderate, and none caused study discontinuation. Four children developed antidrug antibodies (three were neutralizing). After VA treatment, all children improved in one or more efficacy assessments of serum oligosaccharide concentrations (decreases), hearing, immunological profile, and quality of life, suggesting a beneficial effect of early treatment. Although the small study size limits conclusions, these results suggest that long‐term VA treatment has an acceptable safety profile, is well tolerated, and may provide potential benefits to patients with AM under 6 years of age.

News (Medical) associated with Velmanase alfa-tycv

08 Feb 2024

·www.prnewswire.com

Chiesi Global Rare Diseases Presents Long-Term Data on Treatment with Velmanase Alfa in Alpha-Mannosidosis and Announces Additional Presentations at the 20th Annual WORLDSymposium™ Research Meeting

- Results presented from over a decade of treatment with velmanase alfa in alpha-mannosidosis – - Company also presents immunogenicity and tolerability data from pegunigalsidase alfa clinical trial program in Fabry disease – - Additional presentations provide new insights on prevalence, diagnosis, and progression of these rare lysosomal storage disorders – BOSTON, Feb. 8, 2024 /PRNewswire/ -- Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, today announced the presentation of long-term data from up to 12 years of treatment with velmanase alfa in patients with alpha-mannosidosis (AM). The company also announced the presentation of immunogenicity and tolerability data from its pegunigalsidase alfa clinical trial program in Fabry disease, as well as analyses of the prevalence, diagnosis, and progression of these rare lysosomal storage disorders. The data are being presented during the 20th Annual WORLDSymposium™ Research Meeting that is being held February 4-9, 2024, in San Diego, California. "This year's WORLDSymposium marks a significant moment for people living with rare lysosomal storage disorders including alpha-mannosidosis and Fabry disease, and their healthcare teams including clinicians and nurses, who now have access to recently approved treatment options and an important opportunity to understand the impact of these therapies and the barriers that must be addressed to improve diagnosis and disease management," said Giacomo Chiesi, head of Chiesi Global Rare Diseases. "Our company is driven by a commitment to rare disease communities around the world and we are taking full advantage of this conference to share our extensive clinical research in AM, which now spans more than a decade, and in Fabry disease, where we are continuing to evaluate data from our comprehensive development program. We are also emphasizing the importance of the caregiver and patient voice, reporting results from a range of surveys and analyses, hosting symposia, and presenting a special film screening that will help healthcare professionals identify and treat people in these communities in the years ahead." Results from long-term treatment with velmanase alfa in AM In an oral session, Prof. Nathalie Guffon, M.D., Reference Centre of inherited metabolic disease in Femme Mère Enfant Hospital, Hospices Civils of Lyon, France, is presenting results of an analysis that evaluated long‑term efficacy of up to 12 years of treatment with velmanase alfa, which is the first and only enzyme replacement therapy (ERT) available for people with AM. Pooled analyses demonstrate tolerability of pegunigalsidase alfa in Fabry disease and low incidence of de novo anti-drug antibodies Several poster presentations are highlighting immunogenicity and tolerability data from the pegunigalsidase alfa clinical trial program in Fabry disease. John Bernat, M.D., Ph.D., Medical Director of the Iowa Lysosomal Storage Disorders Center, is presenting a poster describing characteristics of anti-drug antibodies (ADAs) reacting with pegunigalsidase alfa, and the patients who develop ADAs, using data from an integrated clinical trial dataset. The analysis includes 108 patients, 27 (25%) of whom were ADA+ before receiving their first dose of pegunigalsidase alfa. There was a low incidence of de novo ADAs (n=17) occurring predominantly in the first year of treatment with pegunigalsidase alfa. Neutralizing antibodies were detected in <25% of patients with de novo ADAs versus in almost all patients who were ADA+ at baseline. In separate poster presentations, Derralynn Hughes, M.D., Professor of Experimental Haematology at the University College London, and Ankit Mehta, M.D., FASN, Baylor University Medical Center, are sharing results from analyses of the tolerability of pegunigalsidase alfa across the clinical program per dosing regimen and prior enzyme replacement therapy (ERT) experience, respectively. Dr. Hughes found that less than a third of patients receiving pegunigalsidase alfa experienced infusion related reactions (IRRs), most of which occurred from the start of the infusion until up to two hours after its end among patients with pre-existing or de novo ADAs. The frequency of IRRs decreased over time and in parallel with a decrease in premedication use among those switching from prior ERT. Dr. Mehta found that IRRs from the start of the infusion until up to two hours after its end occurred in about a quarter of either ERT-naive or ERT-switch patients following treatment with pegunigalsidase alfa. Most of these IRRs were mild to moderate in severity and occurred predominantly in the first year after initiating the therapy. Surveys and epidemiological analyses shed new light on the prevalence, diagnosis, and progression of AM and Fabry disease Chiesi Global Rare Diseases is announcing five additional presentations focused on improving awareness and understanding of the patient experience with rare lysosomal storage disorders including AM and Fabry disease. In an oral presentation, Stuart Gaffney, M.D., Medical Manager, Chiesi Global Rare Diseases, is sharing results from interviews and surveys with Fabry disease patients (n=20), nurses, and clinicians to understand the diagnostic journey and identify unmet medical education needs of UK primary and specialty healthcare professionals. The most common first symptom of Fabry disease was neuropathic pain, and the first severe indication for many patients was chest pain and general heart complaints. Cardiologists were the main specialists identifying Fabry disease, and 55% (11/20) of patients saw a cardiologist who was the first to suspect Fabry disease was the cause of their symptoms. In a poster presentation, Patricia Dorling, Head of Global Health Economics and Outcome Research (GHEOR), Chiesi USA, is reporting results from a study that analyzed data from the Adelphi Fabry Disease Specific Programme™ (DSP), a national representative online survey of physicians treating patients with a confirmed diagnosis of Fabry disease in the United States. Results demonstrate that the burden of complications and use of medical services (HCRU) is substantial with 76% of patients undergoing routine clinical examinations over two years and 19% of patients being hospitalized due to Fabry disease over one year. In a poster presentation, Khashayar Azimpour, M.D., Ph.D., Director, Global Health Economics and Outcome Research (GHEOR), Chiesi USA, is reporting results from a study aimed to estimate diagnosed Fabry disease prevalence and treatment rates in the U.S. via a retrospective cohort analysis. The 2021 diagnosed prevalence was 5,462 people, and 3,747 of those people with Fabry disease had received treatment. The findings highlight potentially higher gender disparities in treatment than previous estimates, signifying greater need for treatment in females. In a poster presentation, Nicole Muschol, M.D., International Center for Lysosomal Disorders (ICLD) at the University Medical Center Hamburg-Eppendorf in Germany, is reporting results from a Delphi study that generated 60 internationally applicable best practice recommendations for the initial assessment of newly diagnosed AM patients and their routine follow-up and integrated care coordination. In a poster presentation, Prof. Guffon is highlighting results from an international caregiver and patient survey designed to assess the impact of AM on patients' functional ability and quality of life. Results confirm that an important treatment goal is stabilizing and slowing disease progression. Untreated patients reported deterioration at a functional, pain and quality of life level, while patients treated with ERT or allogeneic haematopoietic stem cell transplantation reported less decline in walking ability and improved ability to self-care. Chiesi Global Rare Diseases is sponsoring three satellite symposia during WORLDSymposium to review perspectives on the management of Fabry disease and AM including insights from clinicians, caregivers, and patients. The company is also presenting a special screening of "Rare Land," a film focused on AM, with an expert panel featuring Robert Hopkin, M.D., Clinical Geneticist at Cincinnati Children's Hospital Medical Center and Martin Magner, M.D., Ph.D., Department of Paediatrics and Hereditary Metabolic Disorders of the General University Hospital of Prague. In addition, the company is presenting during the Industry Expert Theater session and is participating in the Patient Voice and Preference meeting. Indication and Important Safety Information for Elfabrio® (pegunigalsidase alfa-iwxj) Indication Elfabrio® (pegunigalsidase alfa-iwxj) is indicated for the treatment of adults with confirmed Fabry disease. Important Safety Information Prior to Elfabrio administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions (IARs), and instruct them to seek medical care immediately if such symptoms occur. If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Elfabrio administration and initiate appropriate medical treatment. If a mild to moderate hypersensitivity reaction or IAR occurs, consider slowing the infusion rate or temporarily withholding the dose. In clinical trials, 20 (14%) Elfabrio-treated patients experienced hypersensitivity reactions. Four Elfabrio-treated patients (3%) experienced anaphylaxis reactions that occurred within 5 to 40 minutes of the start of the initial infusion. The signs and symptoms of hypersensitivity reactions and anaphylaxis included headache, nausea, vomiting, throat tightness, facial and oral edema, truncal rash, tachycardia, hypotension, rigors, urticaria, intense pruritus, moderate upper airway obstructions, macroglossia, and mild lip edema. In clinical trials, 41 (29%) Elfabrio-treated patients experienced one or more infusion-associated reactions, including hypersensitivity, nausea, chills, pruritus, rash, chest pain, dizziness, vomiting, asthenia, pain, sneezing, dyspnea, nasal congestion, throat irritation, abdominal pain, erythema, diarrhea, burning sensation, neuralgia, headache, paresthesia, tremor, agitation, increased body temperature, flushing, bradycardia, myalgia, hypertension, and hypotension. A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitor serum creatinine and urinary protein-to-creatinine ratio. If glomerulonephritis is suspected, discontinue treatment until a diagnostic evaluation can be conducted. When switching to Elfabrio from a prior enzyme replacement therapy, the risk of hypersensitivity reactions and infusion-associated reactions may be increased in certain patients with pre-existing anti-drug antibodies (ADAs). Consider monitoring IgG and IgE ADAs and clinical or pharmacodynamic response (eg, plasma lyso-Gb3 levels). The most common adverse reactions (≥15%) were infusion-associated reactions, nasopharyngitis, headache, diarrhea, fatigue, nausea, back pain, pain in extremity, and sinusitis. Please see Full Prescribing Information for Elfabrio. Indication and Important Safety Information for Lamzede® (velmanase alfa-tycv) Indication Lamzede® (velmanase alfa-tycv) is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. Important Safety Information Considerations Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions (IARs) Prior to Lamzede administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and IARs and instruct them to seek medical care immediately if such symptoms occur. If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Lamzede administration and initiate appropriate medical treatment. In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding the infusion for 15 to 30 minutes, slowing the infusion rate to 25% to 50% of the recommended rate, and initiating appropriate medical treatment. Hypersensitivity Reactions Including Anaphylaxis Anaphylaxis and severe hypersensitivity signs and symptoms included cyanosis, hypotension, emesis, urticaria, erythema, facial swelling, pyrexia, and tremor. Infusion-Associated Reactions (IARs) The most frequent symptoms of IARs that occurred in >10% of the population were pyrexia, chills, erythema, vomiting, cough, urticaria, rash, and conjunctivitis. Females of Reproductive Potential Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if Lamzede is discontinued. For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with Lamzede. Embryo-Fetal Toxicity Based on findings from animal reproduction studies, Lamzede may cause embryo-fetal harm when administered to a pregnant female. Common Adverse Reactions The most common adverse reactions (incidence >20%) are hypersensitivity reactions including anaphylaxis, nasopharyngitis, pyrexia, headache, and arthralgia. Please see Full Prescribing Information for Lamzede. About Chiesi Global Rare Diseases Chiesi Global Rare Diseases is a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have a therapy for all diseases and acts as a force for good, for society and the planet. The goal of the Global Rare Diseases unit is to ensure equal access so as many people as possible can experience their most fulfilling life. The unit collaborates with the rare disease community around the globe to bring voice to underserved people in the health care system. For more information visit . About Chiesi Group Chiesi is an international, research-focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company's mission is to improve people's quality of life and act responsibly towards both the community and the environment. By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi's commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we're part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035. With over 85 years of experience, Chiesi is headquartered in Parma (Italy), operates in 31 countries, and counts more than 6,500 employees. The Group's research and development centre in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden. For further information please visit . Chiesi Group Media Contacts Chiara Travagin Rare Communication Manager Tel: +39 348 8818985 Email: [email protected] Alessio Pappagallo Press Office Manager Tel: +39 339 5897483 Email: [email protected] Adam Daley Berry & Company Public Relations Tel: +1 212 253 8881 Email: [email protected] PP-MULTI-0288 V2.0 SOURCE Chiesi Global Rare Diseases

Clinical Result

02 Jan 2024

·www.fiercepharma.com

2023 drug approvals: After a down year, FDA signs off on a bounty of new meds, including 7 from Pfizer

After signing off on 37 new drugs in 2022, its fewest since 2016, the FDA approved 55 in 2023, the second-most ever by the United States regulator. In 2022, fueled by its powerhouse COVID products, Pfizer became the first company in the history of the biopharma industry to top $100 billion in annual revenue. What would the New York drugmaker do for an encore? In 2023, Pfizer went from generating the most sales in the industry to gaining the most approvals. With seven FDA nods in 2023, Pfizer had more than double that of any other company. It’s also more than twice as many as every drugmaker over each of the last three years. You need to go back to 2019, when Novartis scored six approvals, to find a company that approached what Pfizer accomplished in 2023. Pfizer’s splurge included four approvals in a dizzying five weeks in May and June. And all but one of the seven products has been pegged by analysts as a potential blockbuster. Two of the newly approved Pfizer treatments were acquired with the help of the firepower the company gained with its massive sales of COVID vaccine Comirnaty and antiviral Paxlovid. Pfizer’s new ulcerative colitis drug Velsipity came by way of the company’s 2022 acquisition of Arena Pharmaceuticals for $6.7 billion. New nasal spray migraine therapy Zavzpret arrived by way of Pfizer’s $11.6 billion buyout of Biohaven, which also brought soon-to-be blockbuster migraine drug Nurtec. The new Pfizer products cover a wide swath of indications between multiple myeloma drug Elrexfio, OPKO-partnered growth failure treatment Ngenla, first-in-class alopecia therapy Litfulo, RSV vaccine Abryvso and COVID-19 antiviral Paxlovid, which gained a full approval. Pfizer has never scored in one year with so many diverse products. In 2018, for example, when the company achieved four approvals, all of the blessings were for oncology drugs. Martin Mackay, Ph.D., now the co-founder of Massachusetts biotech RallyBio who formerly guided the R&D efforts at Pfizer, remembers being ridiculed in 2010 when he told Bloomberg Television that the company—which was in a minor lull at the time—and the industry in general were in a “golden age of drug discovery.” These days, Mackay is getting the last laugh. “I was watching what was coming through the pipeline,” Mackay said in a recent interview with Fierce Pharma. “I was watching all the new modalities that were at our fingertips—cell therapy, gene therapy, RNA, interference RNA, messenger RNA, neucleotides, gene editing—my thought then was that 10 years from now it’s gonna be terrific in terms of approvals.” Bounty of approvals in 2023 After 2022 produced just 37 new drug approvals—the fewest by the FDA since 2016—the United States regulator signed off on a bumper crop of 55 new drugs in 2023. The list was the second longest in FDA history, coming up just shy of the single-year record of 59 approvals, which was set in 2018. Since this annual report includes vaccine and biologics approvals, the total haul came to 66 new drugs and biologics. Mackay expects the annual numbers to continue to grow over the next decade. Looking at a list of approvals from a decade or two ago, Mackay said he was struck by the wide variety of modalities on this year's list. "And interestingly, small molecules are still the most," Mackay said. "That doesn't surprise me either because they're proven agents. They haven't stayed the same. The technology to work on small molecules is just so different from when I started in the industry." One potential explanation for the difference between the amount of approvals between 2022 and 2023 were the COVID-related inspection delays which held up some approvals. Another potential reason for the dearth of FDA approvals in 2022 could have been the heat the agency took for its much-criticized 2021 nod for Biogen and Eisai’s Alzheimer’s disease drug Aduhelm. Cancer, as usual, saw the most approvals in 2023 with 16, including four bispecifics in a span of as many months. Two bispecifics for multiple myeloma—Talvey from Johnson & Johnson and Elrexfio from Pfizer—made the grade. There also were two bispecifics approved for B-cell lymphomas—Columvi from Roche and Epkinly from AbbVie and Genmab. Talvey and Epkinly have been tabbed with blockbuster potential. Gene Therapies Two of the most significant green lights came on the same day, Dec. 8, and for the same indication, sickle cell disease. Vertex and CRISPR landed a historic thumbs up for Casgevy, which became the first drug to reach the market developed with the revolutionary CRISPR gene editing technology. Simultaneously, bluebird bio earned its nod for another gene therapy, Lyfgenia. Bluebird priced its treatment at $3.1 million, compared to $2.2 million for Casgevy, raising eyebrows at the time. But good news came days after the approval from bluebird as it signed a reimbursement deal with a major insurer. Two other pricey gene therapies made the grade, as well. The single-dose tab for BioMarin’s Roctavian, which treats hemophilia A, clocks in at $2.9 million. Sarepta broke through with a ballyhooed approval to treat Duchenne muscular dystrophy with Elevidys and priced it to match the hype at $3.2 million. RSV Vaccines Make the Grade Also making major news in 2023 was the long-awaited emergence of RSV vaccines. GSK scored first in May with Arexvy for people 60 and older, followed by Pfizer which gained two nods for Abrysvo. In July, Sanofi and AstraZeneca gained a blessing for their antibody, Beyfortus, to protect infants. By 2028, each of the products is expected to generate sales of between $1.3 and $1.7 billion. The first year of rolling out the RSV antibody didn’t go smoothly, however. In late 2023, amid a shortage of Beyfortus, Sanofi and AZ were scrambling to ramp up manufacturing. The companies were taken to task by U.S. lawmakers, demanding answers for their inadequate preparations. Other Key Approvals In the closely watched Alzheimer’s disease space, Biogen and Eisai won a nod for their treatment Leqembi. The blessing came 19 months after the FDA rejected an advisory committee recommendation and signed off on Biogen’s ill-fated Aduhelm. The FDA blessing of Leqembi even came by way of the same accelerated pathway that facilitated Aduhelm’s highly criticized green light. But there are several reasons to be optimistic about the launch of Leqembi as it posted superior trial results and—in contrast to Aduhelm—its nod was recommended unanimously by a panel of independent advisors, paving the way for a full approval. On the flip side, the FDA rejected Eli Lilly’s touted Alzheimer’s treatment donanemab. But the company appears to be on track for approval in 2024. Other big winners in ’23 Four companies—GSK, Biogen, Chiesi and UCB—secured three approvals each in 2023. The trio for UCB included two nods which came on the same day in October, for plaque psoriasis medicine Bimzelx and myasthenia gravis treatment Zilbrysq. The Belgium-based company also earned a green light for another myasthenia gravis drug with a different mechanism of action, Rystiggo. Biogen’s winners were Qalsody in ALS and two partnered drugs—Alzheimer’s med Leqembi, which it shares with Eisai, and postpartum depression drug Zurzuvae, which it splits with Sage. GSK scored for myelofibrosis drug Ojjaara, kidney disease treatment Jesduvroq and RSV vaccine Arexvy. Chiesi of Italy gained approval for Fulsuvez for a rare skin condition and two enzyme replacement therapies—Lamzede and Elfabrio. Another company that excelled with two major approvals was Astellas. The Japanese company scored with Veozah, a breakthrough treatment for hot flashes and night sweats. It also won approval for Izervay, a treatment for geographic atrophy that it acquired in its $5.9 billion buyout of Iveric Bio in early 2023. Both Veozah and Izervay have been pegged to exceed peak sales of more than $2 billion as the company attempts to compensate for the looming patent cliff for prostate cancer drug Xtandi. Editor's note: The numbers for our annual roundup typically vary slightly from the FDA's official list, because our report includes approvals for biologic therapeutics and vaccines but excludes diagnostic imaging agents, which are represented on the FDA's list.

Drug ApprovalAcquisitionVaccine

10 Nov 2023

·www.pmlive.com

NICE recommends Chiesi’s alpha-mannosidosis enzyme replacement therapy

The National Institute for Health and Care Excellence (NICE) has recommended Chiesi’s Lamzede (velmanase alfa) to treat the non-neurological signs and symptoms of mild-to-moderate alpha-mannosidosis, an extremely rare inherited condition affecting around 25 people in England. The treatment must be started in patients aged under 18 years and can be continued in those who turn 18 while on treatment in line with a commercial agreement, Chiesi said. Alpha-mannosidosis is a lysosomal storage disorder caused by inheriting a faulty copy of the MAN2B1 gene from both parents, resulting in impaired production of the enzyme alpha-mannosidase, which is needed to break down certain sugars in the body. The condition is associated with a broad range of signs and symptoms, including difficulty controlling movement, breathing problems, deafness, speech difficulties and bone abnormalities, and the most severe forms are associated with rapid progression and early death. Lamzede, which is designed to supplement or replace the alpha-mannosidase enzyme via a once-weekly intravenous infusion, is now the first and only enzyme replacement therapy recommended by NICE for the condition. Dr Kamran Iqbal, head of medical affairs, global rare diseases, Chiesi UK and Ireland, said: “We are pleased that eligible patients in England and Wales will now be able to access [Lamzede] on the NHS for the first time. "The discovery and availability of new treatment options is crucial for those affected by this progressive disease, and we have worked tirelessly over several years with key stakeholders including NICE, patient groups and clinicians to address uncertainties that are common in rare diseases and ensure access for those in need.” Bob Stevens, group chief executive of the Society for Mucopolysaccharide Diseases, added: “This marks a real change for this community because now they have the possibility of treatment and this is another example of innovative science benefitting our rare patients.” NICE’s final evaluation of Lamzede comes just two months after the agency recommended another of Chiesi’s enzyme replacement therapies, Elfabrio (pegunigalsidase alfa), to treat adults with Fabry disease, a rare genetic disorder that can lead to progressive damage to vital organs, including the heart, kidney and brain.

Drug ApprovalGene Therapy

100 Deals associated with Velmanase alfa-tycv

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D11024	Velmanase alfa-tycv	A16AB15	DB12374

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Indication	Country/Location	Organization	Date
Alpha-Mannosidosis	EU	CHIESI Farmaceutici SpA	23 Mar 2018
Alpha-Mannosidosis	IS	CHIESI Farmaceutici SpA	23 Mar 2018
Alpha-Mannosidosis	LI	CHIESI Farmaceutici SpA	23 Mar 2018
Alpha-Mannosidosis	NO	CHIESI Farmaceutici SpA	23 Mar 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02478840 (SSIEM2023)	Phase 3	Alpha-Mannosidosis	33	Velmanase alfa 1 mg/kg	plksslkdoe(usyzqzkvvb) = blodjxwenk vabyaktcnp (kzgtteznou ) View more	-	30 Aug 2023
NCT01681953 (FDA) Manual	Phase 3	Alpha-Mannosidosis	25	LAMZEDE	ffxdyisapy(sxlfwpwphf) = eghvzytwje xpepvzvwrg (jaoupjkukw, 8.6) View more	Positive	16 Feb 2023
NCT01681953 (FDA) Manual	Phase 3	Alpha-Mannosidosis	25	placebo	ffxdyisapy(sxlfwpwphf) = iabarhueek xpepvzvwrg (jaoupjkukw, 5.5) View more	Positive	16 Feb 2023
NCT02998879 (FDA) Manual	Phase 2	Alpha-Mannosidosis	5	LAMZEDE	bhebbygaqu(ktqmdmojgi) = uksgkaucer aeyrjwjpct (ynzrjavsxr, 4.27) View more	Positive	16 Feb 2023
SSIEM2022	Not Applicable	Alpha-Mannosidosis	16	Velmanase alfa	ourispmzwl(nxsmrjstxf) = nyaqqrqbeh glgayckyya (vxqhxryoez ) View more	-	30 Aug 2022
NCT02478840 (Pubmed \| J Inherit Metab Dis) Manual	Phase 3	Alpha-Mannosidosis	25	Velmanase alfa	mdrczygupx(fbompcousx) = gpcffkbery qfdgjmqisb (dbdzmftviy, -5.5 to 13.2) View more	Positive	01 Nov 2018
NCT02478840 (Pubmed \| J Inherit Metab Dis) Manual	Phase 3	Alpha-Mannosidosis	25	Placebo	mdrczygupx(fbompcousx) = fdupfhbavx qfdgjmqisb (dbdzmftviy, -10.3 to 28.3) View more	Positive	01 Nov 2018

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