Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

Savarirayan, Ravi; Tofts, Louise; Irving, Melita; Wilcox, William R.; Bacino, Carlos A.; Hoover‐Fong, Julie; Font, Rosendo Ullot; Harmatz, Paul; Rutsch, Frank; Bober, Michael B.; Polgreen, Lynda E.; Ginebreda, Ignacio; Mohnike, Klaus; Charrow, Joel; Hoernschemeyer, Daniel G.; Ozono, Keiichi; Alanay, Yasemin; Arundel, Paul; Kotani, Yumiko; Yasui, Natsuo; White, Klane K.; Saal, Howard M.; Leiva-Gea, Antonio; Luna-González, Felipe; Mochizuki, Hidetaka; Basel, Donald; Porco, Dania M; Jayaram, Kala; Fisheleva, Elena; Huntsman-Labed, Alice; Day, Jonathan

doi:10.1038/s41436-021-01287-7

Cited by 51 publications

(42 citation statements)

References 7 publications

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“…Vosoritide binds to CNP receptors, which reduces FGFR3 activity and thereby stimulates bone growth. Subcutaneous administration of vosoritide improves growth in children 5 years of age and older with open epiphyses (Savarirayan et al 2020 , 2021 ). The most common AEs of vosoritide include injection site reactions, arthralgia, vomiting, and hypotension.…”

Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition (“first-in-indication”), (2) first drug using a novel molecular mechanism (“first-in-class”), and (3) “next-in-class”, i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indication drugs. By treatment area, the largest group is once again cancer drugs, many of which target specific genetic alterations. Every second drug approved in 2021 targets an orphan disease, half of them being cancers. Small molecules continue to dominate new drug approvals, followed by antibodies and non-antibody biopharmaceuticals. In 2021, the FDA continued to approve drugs without strong evidence of clinical effects, best exemplified by the aducanumab controversy.

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Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Recently published follow-up data from the vosoritide phase 2 and phase 3 extension studies showed persistent improvements in annualized growth velocity in treated children with achondroplasia across age categories up to 60 months of treatment [ 11 , 12 ]. Overall, the panelists of the modified Delphi study expect that growth velocity increases with vosoritide will continue beyond 60 months, until final height is reached in individuals starting treatment before puberty and that those starting treatment earlier will more likely achieve a greater final height (Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…Results of the pivotal phase 3 clinical trial showed increases in annualized growth velocity and height Z-scores after 52 weeks of treatment with vosoritide versus placebo and good tolerability [ 10 ]. Two-year follow-up data showed sustained increases in annualized growth velocity, continued improvements in height Z-score, and improvements in upper-to-lower body segment ratio versus untreated patients, without adverse effects on bone maturation [ 11 ]. Sixty-month data from a phase 2 study (N = 35) and its extension (N = 19) reported consistent findings [ 7 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Literature review and expert opinion on the impact of achondroplasia on medical complications and health-related quality of life and expectations for long-term impact of vosoritide: a modified Delphi study

Savarirayan

Baratela

Butt

et al. 2022

Orphanet J Rare Dis

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Background Achondroplasia is associated with disproportionate short stature and significant and potentially severe medical complications. Vosoritide is the first medicine to treat the underlying cause of achondroplasia and data from phase 3 and phase 2 extension studies showed effects on growth and body proportions. However, there are currently no long-term data available on the direct impact on endpoints such as medical complications and health-related quality of life (HRQoL). This study explored the perceived impact of achondroplasia on medical complications, HRQoL, healthcare resource use and mortality, and potential modifying effects of vosoritide, based on published evidence and expert opinion. Structured expert opinion was obtained by an international modified Delphi study among 14 experts in managing achondroplasia performed on a virtual platform and consisting of an explorative phase followed by an anonymous individual rating round. Results Overall, the panelists expect that in individuals starting long-term treatment between 2 years of age and puberty, growth velocity increases observed in the clinical trials will be maintained until final height is reached (92% agreement) and will likely result in clinically meaningful improvements in upper-to-lower body segment ratio (85%). Earlier treatment initiation will likely result in a greater final height (100%) and more likely improve proportionality (92%) than later treatment. Although current data are limited, ≥ 75% of panelists find it conceivable that the earlier long-term treatment is started, the greater the probability of a positive effect on the lifetime incidence of symptomatic spinal stenosis, kyphosis, obstructive sleep apnea, and foramen magnum stenosis. These are among the most clinically important complications of achondroplasia because of their high impact on comorbidity, mortality, and/or HRQoL. A positive effect of vosoritide on the incidence of surgeries through lifetime was considered more likely with earlier long-term treatment (90%). Conclusions This explorative study, based on international expert opinion, provides further insight into the medical and functional impacts of achondroplasia and how these might be modified through long-term use of vosoritide. The results can be used to guide the direction and design of future research to validate the assumptions and to discuss potential treatment outcomes with disease modifying therapies with families and clinicians.

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“…Children and adults with achondroplasia can experience lower quality of life (QOL) than do their counterparts without this condition 13,[20][21][22][23][24][25] . QOL is in uenced by a number of factors including disease severity, height, pain, age, self-esteem, social support, and perceived stigmatization 13,19,20 .…”

mentioning

confidence: 99%

“…These procedures involve multiple surgeries and prolonged recovery 11,24 . As an understanding of the pathogenesis of achondroplasia improves, attention is turning to pharmacologic treatments 6,25,26 . While the potential bene t of pharmacologic treatment is documented in the clinical literature, little is understood about how patients and families view the use of medications to improve endochondral bone growth in order to increase stature and, potentially, to ameliorate complications.…”

mentioning

confidence: 99%

Treatment Goals for Achondroplasia: A Qualitative Study with Parents and Adults

McGraw

Henne²,

Nutter³

et al. 2021

Preprint

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Background: Achondroplasia is characterized by disproportionate short stature accompanied by other changes to the musculoskeletal system. Individuals with this condition typically experience a variety of medical complications. Pharmacologic treatments are being developed for the treatment of achondroplasia. It is important to understand the goals for pharmacologic treatment among those affected by achondroplasia and factors that shape these views. Methods: This qualitative study is based on semi-structured interviews with 19 parents of children with achondroplasia and 5 adults with achondroplasia in the United States. We employed thematic analysis using an iterative process to identify themes across the interviews. Results:Participants had two goals for pharmacologic treatment of achondroplasia: ameliorating complications associated with the condition and increasing stature to overcome functional limitations and psychosocial challenges. Complications of particular concern were chronic pain and surgeries to repair spinal, ENT, and neurological sequelae. Increased height would enhance independence, fitting in socially, and avoiding social stigma. Despite many challenges, parents and adults with achondroplasia expressed that they found ways to adapt and emphasized satisfaction and the positive aspects of their lives. Concerns about medical treatment included fear of loss of their identity as a little person. Conclusions:This study offers evidence about how individuals affected by achondroplasia think about pharmacologic treatment of this condition, including both the benefits of ameliorating complications and increasing height. The findings can offer practical insights for parents of children considering treatment, treating physicians and decision makers evaluating coverage decisions for treatment of achondroplasia.

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Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

Cited by 51 publications

References 7 publications

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Literature review and expert opinion on the impact of achondroplasia on medical complications and health-related quality of life and expectations for long-term impact of vosoritide: a modified Delphi study

Treatment Goals for Achondroplasia: A Qualitative Study with Parents and Adults

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