- SHINE data illustrates SPINRAZA’s longer-term benefits for infantile-onset SMA, including improvements in motor function and increased event-free survival in participants followed for nearly three years
- Additional findings show that later-onset SMA patients treated with SPINRAZA walked longer distances while experiencing stable or less fatigue over time, in contrast to SMA natural history
“These results reinforce SPINRAZA’s unprecedented and compelling
efficacy across a broad range of SMA populations, enabling patients to
improve mobility and motor function – and, for the most severely
affected, increase their chances of survival,” said
The SHINE analysis reported interim results as of
“This analysis demonstrates that participants improved their motor
function and increased event-free survival time, whether they initiated
treatment earlier, as in ENDEAR and continuing in SHINE, or later, after
receiving sham-control in ENDEAR and beginning treatment in SHINE,” said
The interim results showed that participants who initiated SPINRAZA in ENDEAR and continued in SHINE, as well as those who received sham in ENDEAR and initiated SPINRAZA in SHINE, experienced improvements in HINE-2 motor milestones and general motor function as measured by CHOP INTEND. The median time to death or permanent ventilation for participants who initiated SPINRAZA in ENDEAR and continued in SHINE was 73 weeks. Among participants who received sham, the median time to death or permanent ventilation was 22.6 weeks within ENDEAR. The majority of subjects who were alive and did not require permanent ventilation after they received sham in ENDEAR remained event-free after receiving SPINRAZA in SHINE for a median time of 9.2 months.
An additional analysis – which was led by researchers at
“With SPINRAZA treatment, not only were participants able to walk longer
distances but they experienced a stabilization or decrease in fatigue
while doing so – both of which are meaningful, real-world benefits for
individuals with SMA,” said
SHINE is an ongoing Phase 3, multicenter, open-label extension study for patients with SMA who previously participated in the nusinersen clinical trial program, including the CS3A, ENDEAR, CHERISH, CS12 and EMBRACE studies. The primary and secondary objectives of the SHINE study are to evaluate the long-term safety/tolerability and efficacy of nusinersen, respectively. Study participants will be evaluated for up to five years in SHINE.
SPINRAZA Program Status
SPINRAZA is the first and only approved medicine for the treatment of
SMA and is currently approved in
Globally, starting in 2016, in response to the urgent need for treatment for the most severely affected individuals living with SMA, Biogen sponsored one of the largest, pre-approval Expanded Access Programs (EAP) in rare disease, free of charge.
Biogen licensed the global rights to develop, manufacture and
commercialize SPINRAZA from
SMA is characterized by loss of motor neurons in the spinal cord and lower brain stem, resulting in severe and progressive muscular atrophy and weakness. Ultimately, individuals with the most severe type of SMA can become paralyzed and have difficulty performing the basic functions of life, like breathing and swallowing.
Due to a loss of, or defect in, the SMN1 gene, people with SMA do not produce enough survival motor neuron (SMN) protein, which is critical for the maintenance of motor neurons. The severity of SMA correlates with the amount of SMN protein. People with Type 1 SMA, the form that requires the most intensive and supportive care, produce very little SMN protein and do not achieve the ability to sit without support or live beyond two years without respiratory support. People with Type 2 and Type 3 SMA produce greater amounts of SMN protein and have less severe, but still life-altering forms of SMA.
About SPINRAZA® (nusinersen)
SPINRAZA is being developed globally for the treatment of SMA.
SPINRAZA is an antisense oligonucleotide (ASO), using Ionis’ proprietary antisense technology, that is designed to treat SMA caused by mutations or deletions in the SMN1 gene located in chromosome 5q that leads to SMN protein deficiency. SPINRAZA alters the splicing of SMN2 pre-mRNA in order to increase production of full-length SMN protein.6 ASOs are short synthetic strings of nucleotides designed to selectively bind to target RNA and regulate gene expression. Through use of this technology, SPINRAZA has the potential to increase the amount of full-length SMN protein in individuals with SMA.
SPINRAZA must be administered via intrathecal injection, which delivers therapies directly to the cerebrospinal fluid (CSF) around the spinal cord,7 where motor neurons degenerate in individuals with SMA due to insufficient levels of SMN protein.8
SPINRAZA demonstrated a favorable benefit-risk profile. The most common adverse reactions reported for SPINRAZA were upper respiratory infection, lower respiratory infection, and constipation. Serious adverse reactions of atelectasis were more frequent in SPINRAZA-treated patients. Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been observed after administration of some ASOs. Individuals may be at increased risk of bleeding complications. Renal toxicity has been observed after administration of some ASOs. SPINRAZA is present in and excreted by the kidney.
For more information about SPINRAZA and prescribing information in
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Biogen Safe Harbor
This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 relating to the potential benefits, safety, and efficacy of SPINRAZA, the results of certain real-world data, the status of Biogen’s current regulatory filings, Biogen’s plans for additional regulatory filings in other jurisdictions, and availability of patient access and reimbursement pathways, which may vary on a country-by-country basis. These forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “except,” “forecast,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk. You should not place undue reliance on these statements or the scientific data presented.
These statements involve risks and uncertainties that could cause actual
results to differ materially from those reflected in such statements,
including without limitation uncertainty of success in commercialization
of SPINRAZA, which may be impacted by, among other things, the level of
preparedness of healthcare providers to treat patients, difficulties in
obtaining or changes in the availability of reimbursement for SPINRAZA,
the effectiveness of sales and marketing efforts, problems with the
manufacturing process for SPINRAZA, the occurrence of adverse safety
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Investors should consider this cautionary statement, as well as the risk
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1. Darras B, Markowitz J, Monani U,
2. Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell.1995;80(1):155-165.
3. Mailman MD, Heinz JW, Papp AC, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002;4(1):20-26.
4. Monani UR, Lorson CL, Parsons DW, et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999;8(7):1177-1183.
5. Peeters K, Chamova T, Jordanova A. Clinical and genetic diversity of
SMN1-negative proximal spinal muscular atrophies. Brain.2014;
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Antisense correction of SMN2 splicing in the CNS rescues necrosis in a
type III SMA mouse model. Genes Dev. 2010
7. Evers MM, Toonen LJ, van Roon-Mom WM. Antisense oligonucleotides in therapy for neurodegenerative disorders. Adv Drug Deliv Rev. 2015;87:90-103.
8. Lunn MR,