First Year After Launch Special Feature 2018: Don’t look back, someone might be gaining
The top performers of the launch class of 2016 have very little in common – aside from the fact that none of them came from a “classic” big pharma house.
The Pfizers, Roches, and Mercks of the world may still top pharma’s revenue charts, but many of the industry’s most exciting new brands are coming from a very different generation of companies. Gilead, Novo Nordisk, and Biogen – the minds behind the top three new brands launched in 2016 – are a diverse lot with a diverse history, but one characteristic they share is that none of them has ever been a top-five pharma company by sales, and Gilead only reached the top 10 in 2014, its magical first year of Sovaldi. These companies are clearly not part of the ancien régime of pharma, but that has not stopped them from bettering their “betters” in the innovation game.
On June 28th, 2016, FDA approved Gilead Sciences’ Epclusa (sofosbuvir 400 mg/velpatasvir 100 mg), the first all-oral, pan-genotypic, single tablet regimen for the treatment of adults with genotype 1-6 chronic hepatitis C virus infection. Epclusa was also the first single tablet regimen approved for the treatment of patients with HCV genotype 2 and 3, without the need for ribavirin. Epclusa for 12 weeks was approved in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A), and in combination with ribavirin (RBV) for patients with decompensated cirrhosis (Child-Pugh B or C).
“The approval of Epclusa represents an important step forward in the global effort to control and potentially eliminate HCV as it provides a safe, simple and effective cure for the majority of HCV-infected patients, regardless of genotype,” said Ira Jacobson, M.D., chairman of the Department of Medicine at Mount Sinai Beth Israel in New York City and a principal investigator in the Epclusa clinical trials. “Building on the established backbone of sofosbuvir, Epclusa demonstrated consistently high cure rates across all genotypes, including among patients with genotype 2 and 3, who traditionally have required ribavirin or other multi-pill regimens.”
Epclusa’s approval was supported by data from four international Phase III studies, ASTRAL-1, ASTRAL-2, ASTRAL-3, and ASTRAL-4. In the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies, 1,035 patients with genotype 1-6 chronic HCV infection, without cirrhosis or with compensated cirrhosis received 12 weeks of Epclusa. The ASTRAL-4 study randomized 267 patients with genotype 1-6 HCV infection, with decompensated cirrhosis (Child-Pugh B), to receive 12 weeks of Epclusa with or without RBV or 24 weeks of Epclusa. The primary endpoint for all studies was SVR12.
Of the 1,035 patients treated with Epclusa for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved SVR12. In ASTRAL-4, patients with decompensated cirrhosis receiving Epclusa with RBV for 12 weeks achieved a high SVR12 rate (94 percent) compared to those who received Epclusa for 12 weeks or 24 weeks (83 percent and 86 percent, respectively).
“Today’s approval represents a significant advance for patients with HCV genotypes 2 and 3, who previously required more complex and costly regimens,” said John Milligan, Ph.D., president and CEO of Gilead, upon FDA’s announcement. “As the first and only pan-genotypic cure for hepatitis C, Epclusa has the potential to eliminate the need for genotype testing, which can be a barrier to treatment in certain resource-constrained settings. We look forward to making Epclusa available to patients around the world as quickly as possible.”
In August 2017, FDA approved updated labeling for Epclusa to include use in patients co-infected with HIV.
“HCV co-infection remains a major cause of morbidity in HIV-infected individuals,” said David Wyles, M.D., chief, Division of Infectious Disease, Denver Health Medical Center; associate professor of medicine, University of Colorado School of Medicine. “With this expanded use, Epclusa provides co-infected patients with a much needed one-pill-a-day regimen that works across all HCV genotypes and is compatible with widely-used antiretroviral regimens. With Epclusa, physicians have an important new treatment option for their HCV/HIV co-infected patients.”
The supplemental new drug application was supported by data from the open-label, Phase III ASTRAL-5 study, which evaluated 12 weeks of treatment with Epclusa in 106 subjects with genotype 1-4 HCV infection who were co-infected with HIV and on stable antiretroviral therapy. In the study, 95 percent (101/106) of patients achieved the primary endpoint of SVR12, defined as an undetectable viral load 12 weeks after completing therapy. The safety profile of Epclusa in HCV/HIV co-infected patients was similar to that observed in HCV mono-infected patients. The most common adverse events (in at least 10 percent of subjects) were fatigue (22 percent) and headache (10 percent).
“Epclusa has already helped further simplify HCV treatment among mono-infected patients, and we are pleased that HCV/HIV co-infected patients can benefit from this pan-genotypic single tablet regimen,” Dr. Milligan said. “This approval advances the commitment we’ve made to the HCV and HIV communities to deliver innovative new treatments that address their unmet medical needs.”
This past May, the China Drug Administration approved Epclusa for the treatment of adults with genotype 1-6 chronic hepatitis C virus infection. The CDA also approved Epclusa in combination with ribavirin for adults with HCV and decompensated cirrhosis. Epclusa is the first pan-genotypic HCV single tablet regimen approved in China. According to published reports, there are nearly 10 million hepatitis C patients in China, and 240,000 new patients were diagnosed in 2017.
The approval of Epclusa in China was supported by the five international Phase III ASTRAL studies. High overall rates of SVR12, ranging from 92-100 percent, were achieved across difficult-to-cure patient populations including treatment-experienced patients and those with compensated or decompensated cirrhosis.
“The safety and efficacy profile of Epclusa are supported by large clinical and real-world global datasets,” said Professor Lai Wei, Peking University People’s Hospital and Institute of Hepatology, Peking University. “With high cure rates across all HCV genotypes, Epclusa could increase HCV treatment in China by potentially eliminating the need for genotype testing, which can be a barrier to treatment in many settings.”
Tresiba earned its first FDA approval in September 2015, for use alone, or in combination with oral antidiabetic medicines or bolus insulin, for glycemic control in adults with type 1 and type 2 diabetes. The medicine earned a subsequent approval for use by children and adolescents with diabetes in December 2015, and was launched broadly in the United States by Novo Nordisk in January 2016.
The initial approval was based on data from the BEGIN clinical trial program and included an interim analysis of DEVOTE, the cardiovascular outcomes trial for Tresiba. The BEGIN clinical trial program included nine randomized, controlled, treat-to-target, open-label trials in patients with type 1 and type 2 diabetes from more than 40 countries. FDA concluded based on the provided data that Tresiba improves glycemic control, achieving comparable A1C reductions (noninferiority) to FDA-approved comparators.
The pediatric approval was based on the results of the BEGIN Young 1 trial, a multinational, 26-week, phase IIIb, randomized, controlled, open-label, parallel-group, treat-to-target non-inferiority trial with a 26-week extension. BEGIN Young 1 compared the efficacy and safety of Tresiba administered once-daily compared with Levemir (insulin detemir [rDNA origin] injection) administered once-daily or twice-daily, both in combination with insulin aspart, a mealtime insulin, in children and adolescents with type 1 diabetes aged 1 to 17. The results showed that Tresiba in combination with insulin aspart effectively improved glycemic control.
A few days after the product was launched in the United States, Novo Nordisk announced the headline results from SWITCH 2, the first of two 2 x 32-weeks randomized, double-blind, cross-over, treat-to-target trials, comparing the safety and efficacy of Tresiba (insulin degludec) and insulin glargine. The overall purpose of the trial was to compare the hypoglycemia occurrence in people with type 2 diabetes treated with Tresiba or insulin glargine.
In the clinical trial, 721 people with type 2 diabetes were randomized to cross-over treatment with Tresiba and insulin glargine in combination with metformin. The timing of the daily injections of both Tresiba and insulin glargine was randomized equally to take place either in the morning or evening. The primary end-point of the study was the number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycemia episodes during the maintenance period (ie after 16 weeks of treatment) in each treatment period.
From a mean baseline of 7.6 percent, the trial showed non-inferiority in HbA1c reduction of Tresiba compared to insulin glargine, thus fulfilling the requirements for objectively comparing hypoglycemia rates between the two treatments. Likewise, the end-of-trial insulin doses were similar at the end of treatment in the two treatment periods.
The observed rate of severe or blood glucose confirmed symptomatic hypoglycemia was 186 events per 100 patient years exposed to Tresiba and 265 events per 100 patient years exposed to insulin glargine during the maintenance period. This reduction was statistically significant, and the trial thus met its primary endpoint by demonstrating a reduction of 30 percent when people were treated with Tresiba compared to insulin glargine. The observed rate of severe or blood glucose symptomatic nocturnal confirmed hypoglycemia in the maintenance period was 55 events per 100 patient years exposed to Tresiba and 94 events per 100 patient years exposed to insulin glargine, corresponding to a 42 percent reduction with Tresiba compared to insulin glargine and showing statistical significance on this confirmatory secondary end-point.
The following month, Novo Nordisk announced the headline results from SWITCH 1, the second of the two 2 x 32-weeks trials, comparing the safety and efficacy of Tresiba (insulin degludec) and Lantus (insulin glargine U100). The overall purpose of the trial was to compare the hypoglycemia occurrence in people with type 1 diabetes treated with Tresiba or insulin glargine.
In the study, 501 people with type 1 diabetes were randomized to cross-over treatment with Tresiba and insulin glargine U100 in combination with insulin aspart. The timing of the daily injections of both Tresiba and insulin glargine was randomized equally to take place either in the morning or evening. The primary end-point of the clinical trial was the number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycemia episodes during the maintenance period (ie after 16 weeks of treatment) in each treatment period.
From a mean baseline of 7.6 percent, the trial showed non-inferiority in HbA1c reduction for Tresiba compared to insulin glargine, thus fulfilling the requirements for objectively comparing hypoglycemia rates between the two treatments. Likewise, the end-of-trial insulin doses were similar at the end of treatment in the two treatment periods.
The trial met the primary end-point by demonstrating non-inferiority in the rate of severe or blood glucose confirmed symptomatic hypoglycemia of Tresiba compared to insulin glargine. The observed rate was 2,201 events per 100 patient years exposed to Tresiba and 2,463 events per 100 patient years exposed to insulin glargine during the maintenance period, corresponding to a statistically significant reduction of 11 percent.
Similarly, non-inferiority was shown for the rate of severe or blood glucose confirmed symptomatic nocturnal hypoglycemia in the maintenance period. The observed rate of severe or blood glucose confirmed symptomatic nocturnal hypoglycemia was 277 events per 100 patient years exposed to Tresiba and 429 events per 100 patient years exposed to insulin glargine, corresponding to a statistically significant 36 percent reduction with Tresiba compared to insulin glargine.
In November 2016, FDA approved Xultophy 100/3.6, a once-daily single injection fixed combination of Tresiba and Victoza. Xultophy is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (less than 50 units daily) or liraglutide (less than or equal to 1.8 mg daily).
In the DUAL Phase III clinical trial program, Xultophy 100/3.6 consistently showed an improvement of glycemic control in adults with type 2 diabetes uncontrolled on liraglutide or basal insulin therapy. For adults inadequately controlled on insulin glargine U100, treatment with Xultophy 100/3.6 demonstrated a reduction in HbA1c of 1.7 percent after 26 weeks.
In June 2017, Novo Nordisk announced that results of the EU-TREAT study showed that people with type 1 diabetes and type 2 diabetes experienced a significant reduction in HbA1c (-0.2 percent for type 1 diabetes and -0.5 percent for type 2 diabetes) 6 months after switching to Tresiba from another basal insulin, primarily insulin glargine U100 and insulin detemir, in a real-world setting. These results were sustained at 12 months. Rates of overall hypoglycemia were also significantly lower at 6 months after switching to Tresiba. In people with type 1 diabetes, the rate of severe hypoglycemia was reduced by 85 percent and by 92 percent in people with type 2 diabetes. Hypoglycemia outcomes at 12 months were in line with these results.
In addition, a significant reduction in fasting plasma glucose was observed at 6 months (-18.7 mg/dL for type 1 diabetes, and -23.7 mg/dL for type 2 diabetes) and maintained for 12 months. The total daily insulin dose also decreased significantly in people with type 1 diabetes (-4.9 units) and type 2 diabetes (-2.5 units) at 6 months, and remained stable at 12 months.
Also in June 2017, Novo Nordisk announced the primary results from DEVOTE – the first randomized, double-blind, treat-to-target, event-driven trial comparing two basal insulins,
Tresiba and insulin glargine U100, in adults with type 2 diabetes at high risk of cardiovascular disease. The trial demonstrated that Tresiba met the primary endpoint of non-inferiority compared with insulin glargine U100 for major adverse CV events (MACE) with a hazard ratio (HR) of 0.91. Additionally, the findings for each component of MACE were consistent with the primary endpoint, including first occurrence of CV death. FDA approved an update to the Tresiba label to include data from DEVOTE this past March.
During November, Novo Nordisk announced that an analysis of real-world data showed that switching to Tresiba is highly cost-effective and cost-saving for the treatment of type 1 and type 2 diabetes, respectively. Tresiba remained cost-effective even after excluding key benefits associated with switching to Tresiba such as reductions in hypoglycemia (low blood sugar levels) and the use of health system resources in a calculation based on a treatment period of one year. When estimating the lifetime cost of diabetes, cost savings were even greater.
In March, FDA approved updates to the prescribing information for Tresiba to include data from the DEVOTE safety outcomes trial. The following data from DEVOTE in patients with type 2 diabetes and atherosclerotic cardiovascular disease is now included in the label:
• Primary composite endpoint: Tresiba U-100 showed no increased risk of major adverse cardiovascular events (MACE) with a hazard ratio of 0.91 compared to insulin glargine U-100. MACE in the DEVOTE trial is defined as the first occurrence of cardiovascular death, non-fatal heart attack, or non-fatal stroke.
• Secondary confirmatory endpoint: Tresiba U-100 showed 40 percent significantly lower rates of severe hypoglycemia (low blood sugar) compared to insulin glargine U-100.
Blood sugar control between the two groups was similar at baseline and throughout the trial. In DEVOTE, severe hypoglycemia was defined as having a low blood sugar level that requires assistance from another person to treat.
“Tresiba is clinically proven to lower patients’ A1C levels, and now the updated label provides physicians with additional clinical evidence to help guide treatment decisions,” said Todd Hobbs, M.D., VP and US chief medical officer of Novo Nordisk, after the label update. “Cardiovascular disease and severe hypoglycemia are two of the most profound concerns for people living with diabetes. Novo Nordisk is dedicated to research in these areas and believes in their importance to overall diabetes care.”
In June, Novo Nordisk announced that findings from CONFIRM – a large, retrospective real-world evidence study comparing the effectiveness of Tresiba versus insulin glargine U-300 in more than 4,000 adults with type 2 diabetes who were starting basal insulin for the first time – showed that after six months those treated with Tresiba had significantly lower A1C compared to those treated with insulin glargine U-300 (-1.5 percent versus -1.2 percent respectively).
As a secondary endpoint, there was a 30 percent lower rate of hypoglycemic episodes with Tresiba compared to insulin glargine U-300. The study also showed in another secondary endpoint that people treated with Tresiba were more likely to stay on their treatment. Those treated with insulin glargine U-300 had a 37 percent higher rate of discontinuing treatment after two years.
“Real-world studies, such as CONFIRM, are important to understand how clinical trials may translate to patients in everyday clinical practice,” Dr. Hobbs says. “One of the most feared complications for people living with diabetes is hypoglycemia, and the CONFIRM results add to the body of evidence on Tresiba for adults with type 2 diabetes.”
Biogen’s Spinraza was approved by FDA in December 2016 under priority review for the treatment of spinal muscular atrophy in pediatric and adult patients. Spinraza was the first and remains the only treatment approved in the United States for SMA, a leading genetic cause of death in infants and toddlers that is marked by progressive, debilitating muscle weakness. The compound was subsequently approved in the EU during June 2017.
In ENDEAR, a pivotal controlled clinical study, infantile-onset SMA patients treated with Spinraza achieved and sustained clinically meaningful improvement in motor function compared to untreated study participants. In addition, a greater percentage of patients on Spinraza survived compared to untreated patients.
In open-label studies, some patients achieved milestones such as ability to sit unassisted, stand, or walk when they would otherwise be unexpected to do so and maintained milestones at ages when they would be expected to be lost.
The overall findings of these studies support the effectiveness of Spinraza across the range of SMA patients, and appear to support the early initiation of treatment.
“Spinraza offers new hope for the SMA community and exemplifies our mission of applying cutting-edge science to make a meaningful difference in the lives of patients with devastating, life-altering diseases,” said George A. Scangos, Ph.D., CEO at Biogen, in the U.S. approval announcement. “We are humbled and grateful for the commitment of the patients and families who participated in the Spinraza clinical trial program, the tireless efforts of our investigators, and the urgency demonstrated by the FDA in rapidly reviewing and approving this treatment. We also want to acknowledge the important work of our colleagues at Ionis, who initiated this program.”
Spinraza’s approval was based on positive results from multiple clinical studies in more than 170 patients. The data package included the interim analysis of ENDEAR, a Phase III controlled study evaluating Spinraza in infantile-onset, as well as open-label data in pre-symptomatic and symptomatic patients with, or likely to develop, Types 1, 2, and 3 SMA.
In April 2017, Biogen presented Phase III end of study Spinraza data from CHERISH, which demonstrated a highly statistically significant and clinically meaningful improvement in motor function in children with later-onset (most likely to develop Type 2 or Type 3) spinal muscular atrophy compared to untreated children. The 15-month study investigated Spinraza in 126 non-ambulatory children 2 to 12 years old who experienced symptom onset at greater than 6 months of age.
In the CHERISH end of study analysis, children on Spinraza demonstrated a highly statistically significant and clinically meaningful improvement in motor function, as observed by the treatment difference of 4.9 points in the mean change from baseline to Month 15 in the Hammersmith Functional Motor Scale Expanded (HFMSE) score. The HFMSE is a validated tool specifically designed to assess motor function in children with SMA. When measuring changes from baseline, children who received Spinraza achieved a 3.9 point mean improvement at Month 15, while children who were not on treatment experienced a mean decline of 1.0 point. Primary endpoint results of the end of study analysis were consistent with results observed at the interim analysis. Data from the other endpoints analyzed, including attainment of new motor milestones and upper limb motor function, were consistently in favor of children who received treatment.
In March, Biogen announced new interim Phase II results from NURTURE, the ongoing open-label, single-arm study evaluating the efficacy and safety of Spinraza among pre-symptomatic infants with spinal muscular atrophy. In NURTURE, all infants treated with SPINRAZA were alive, did not require permanent ventilation and showed improvement in motor function and motor milestone achievements as of July 5, 2017, compared to the disease’s natural history.
In the NURTURE study, Spinraza was administered to infants six weeks old or younger, who were in the pre-symptomatic stage, genetically diagnosed with SMA, and had two or three copies of the SMN2 gene. At the time of this interim analysis, infants had been followed for up to 25.6 months – well beyond the typical timeframe when most infants with Type 1 SMA would have required permanent ventilation or died. The interim analysis showed that all infants were alive and none required tracheostomy or permanent ventilation.
“The NURTURE findings document the continuing benefits that Spinraza provides for patients with SMA who initiated treatment in early infancy while clinically pre-symptomatic, including age-appropriate developmental gains in motor function and motor milestone achievements,” said Dr. Darryl C. De Vivo, M.D., lead study author, Columbia University Medical Center, New York. “The treated infants in the NURTURE study had genetic SMA and were likely to clinically develop Type 1 or 2, yet with enough observation time they have all achieved independent sitting and the majority have developed the ability to walk.”
NURTURE participants additionally achieved a mean CHOP INTEND score, which measures general motor function among infants with SMA, of 58.4 at last visit (out of a maximum score of 64). Many continue to improve and maintain these scores beyond a point in time at which untreated individuals with Type 1 SMA would experience a significant decline.
Biogen and Ionis Pharmaceuticals, its development partner for Spinraza, during April announced an expansion of their strategic collaboration through a new ten-year collaboration agreement to develop novel antisense drug candidates for a broad range of neurological diseases. According to company leaders, this collaboration capitalizes on Biogen’s expertise in neuroscience research and drug development and Ionis’ leadership in RNA targeted therapies with the goal of developing a broad pipeline of investigational therapies. The companies plan to advance programs for a broad range of neurological diseases for which few treatment options exist today. Disease areas include dementia, neuromuscular diseases, movement disorders, ophthalmology, diseases of the inner ear, and neuropsychiatry. Biogen will have the first choice of neurology targets on which to exclusively collaborate with Ionis. Ionis is responsible for the identification of antisense drug candidates based on selected targets. Biogen is responsible for and paying for non-clinical studies, clinical development, manufacturing, and commercialization.
Also during April, Biogen announced new findings detailing the benefits that Spinraza demonstrates for both infantile- and later-onset spinal muscular atrophy populations, including improvement in motor function as well as increased survival for the most severely affected. These findings were based on interim results from the SHINE open-label extension study and an analysis of Spinraza’s effects on mobility and fatigability in later-onset participants from the CS2/CS12 studies.
“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 Alfred Sandrock, M.D., Ph.D., executive VP and chief medical officer at Biogen. “We look forward to continuing to work with healthcare providers, institutions and SMA communities to provide access to Spinraza for those in need, no matter their age, disease severity or duration of the disease.”
The SHINE analysis reported interim results as of June 30, 2017, from the open-label extension study for patients with infantile-onset SMA (most likely to develop Type 1) who transitioned from the Phase III ENDEAR study. Participants either initiated Spinraza treatment in ENDEAR and continued treatment through SHINE or transitioned from the sham-control arm in ENDEAR to active treatment with Spinraza in SHINE.
“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 Diana Castro, M.D., lead study author, UT Southwestern Medical Center, Dallas, Texas. “It also confirms that those who initiated Spinraza treatment earlier saw greater motor milestone performance that continued to improve over time, and that no new safety concerns were identified.”
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, led by researchers at Columbia University Medical Center with support from Biogen, evaluated a subset of data from CS2 and CS12, two multicenter, open-label clinical trials, to assess the change in participants’ performance during the Six-Minute Walk Test and measures of fatigue. The analysis examined the walking ability and fatigability of ambulatory participants ages two to 15 years with SMA Type 2 or Type 3 at study enrollment. Participants’ baseline median distance walked was 250.5 meters and baseline median fatigue level was 14.8 percent. Following Spinraza treatment, their walking distance increased (a median increase of 98 meters) while simultaneously, their fatigue level remained stable or decreased (a median decrease of 3.8 percent) over nearly 3 years.
In July, a study published in the Journal of Neuromuscular Diseases found that children with SMA type 1 can achieve improvements in motor function after six months of treatment with the Spinraza, particularly when treatment began before seven months of age. According to the authors, these findings highlight the importance of early detection of SMA through newborn screening.
“Our findings add to the increasing body of evidence that early diagnosis and initiation of treatment is fundamental for patients with infantile-onset spinal muscular atropy,” said lead investigator Janbernd Kirschner, MD, of the Department of Neuropediatrics and Muscle Disorders, Medical Center, Faculty of Medicine, University of Freiburg, and Coordinator of the TREAT-NMD Clinical Trial Coordination Centre (CTCC), Freiburg (Germany).
SMA type 1 is the most common and also most severe subtype of SMA. After diagnosis infants with SMA type 1 rarely achieve improvements of motor function or attain motor developmental milestones. Prior to approval in Europe, Spinraza was provided to patients with SMA type 1 within an Expanded Access Program. In contrast to the previous clinical trials, children of different age groups and different stages of the disease were treated with Spinraza within the EAP.
The prospective, open-label study conducted in Germany reported outcomes from 61 children with SMA type 1 treated with Spinraza between November 2016 and June 2017 who met EAP guidelines. Patients ranged in age from a few months to almost 8 years. Symptoms generally appeared within the first three months of life and most babies were diagnosed before six months of age. Prior to treatment, more than half of the children required ventilation support, 20 percent had already undergone a tracheostomy, and more than half required a feeding tube.
Although improvements in motor function are not expected within the natural course of the disease, the researchers observed improvements in motor function after six months of Spinraza therapy in many patients, and 34 percent of the patients achieved new motor developmental milestones. The response to treatment strongly correlated with age at onset of treatment. Overall, greater improvements were seen in children who began treatment at seven months or younger compared to those who started treatment after seven months. Improvements could still be seen in patients who started therapy between two and four years of age, although the magnitude of the changes was less than those for infants. Despite six months of treatment, none of the children were able to stand or walk independently, and many still required ventilator support and tube feeding.
The findings of this study, its authors suggest, add to the increasing body of evidence that early diagnosis and initiation of treatment are fundamental for patients with infantile onset spinal muscular atrophy, highlighting the importance of the implementation of a newborn screening. “We have evidence that there is a critical therapeutic time window for delivery of SMN-targeted therapies,” Dr. Kirschner said. “The implementation of newborn screening for SMA is crucial to allow pre-symptomatic diagnosis.”
For a listing of 2017’s best-selling new molecular entities that were launched in the United States during 2016, please click here: MAN0818_FYAL_Chart