SPINRAZA (Nusinersen) Approved in the European Union as First Treatment for Spinal Muscular Atrophy

It is cool news for all patient with SMA.

CAMBRIDGE, Mass.--(BUSINESS WIRE)--The European Commission (EC) has granted a marketing authorization for SPINRAZA® (nusinersen) for the treatment of 5q spinal muscular atrophy (SMA), Biogen (NASDAQ:BIIB) announced today. 5q SMA is the most common form of the disease and represents approximately 95% of all SMA cases. SPINRAZA is the first approved treatment in the European Union (EU) for SMA, a leading genetic cause of death in infants that is marked by progressive, debilitating muscle weakness. SPINRAZA was reviewed under the European Medicines Agency’s (EMA) accelerated assessment program, intended to expedite access to patients with unmet medical needs.

“Today we join individuals and families affected by SMA across Europe in celebrating the approval of SPINRAZA. Based on the robust efficacy and safety profile demonstrated in the clinical trials, we believe SPINRAZA will have a meaningful impact on infants, children and adults living with this devastating disease,” said Michel Vounatsos, chief executive officer at Biogen. “As part of our mission to improve the lives of those affected by SMA, we remain steadfast in our commitment to work with healthcare professionals, advocacy groups and government agencies to ensure people who could benefit from SPINRAZA receive access to this important treatment as quickly as possible.”

The approval of SPINRAZA is primarily based on results from two pivotal multicenter, controlled studies, including end of study data from ENDEAR (infantile-onset SMA) and an interim analysis of CHERISH (later-onset SMA), both of which demonstrated the clinically meaningful efficacy and favorable benefit-risk profile of SPINRAZA. The approval was also supported by open-label data in pre-symptomatic and symptomatic individuals with, or likely to develop, Types 1, 2 and 3 SMA.

In the ENDEAR end of study analysis, a statistically significant greater percentage of patients achieved the definition of motor milestone responder in the SPINRAZA group (51%) compared to the sham-control group (0%) (p<0.0001). Some infants in the SPINRAZA group achieved motor milestones including full head control, ability to roll, sitting, and standing. Additionally, infants treated with SPINRAZA demonstrated a statistically significant reduction (47%) in the risk of death or permanent ventilation (p=0.0046). In the CHERISH pre-specified interim analysis, there was a statistically significant and clinically meaningful improvement in motor function in children with later-onset SMA (most likely to develop Type 2 or Type 3) treated with SPINRAZA compared to untreated children. Improvements were measured by the Hammersmith Functional Motor Scale Expanded (HFMSE) and demonstrated a treatment difference of 5.9 points in the mean change from baseline to Month 15 in the HFMSE score (p=0.0000002). The HFMSE is a reliable and validated tool specifically designed to assess motor function in children with SMA. The Phase 3 end of study data were consistent with the interim analysis and presented at the American Academy of Neurology annual meeting in Boston, Mass., April 2017. “The overall clinical findings support the efficacy and safety of SPINRAZA in a broad range of individuals with SMA, including significant improvements in motor development and reduction in risk of death in infants,” said Prof. Dr. Jan Kirschner from the Medical Center University of Freiburg, Germany. “These unprecedented improvements bring new hope to a community where there previously were no approved treatments available to address the loss of motor function over time. We are now seeing motor improvements with SPINRAZA that are never seen in the natural course of the disease.” SPINRAZA must be administered via intrathecal injection, which delivers therapies directly to the cerebrospinal fluid (CSF) around the spinal cord,3 where motor neurons degenerate in individuals with SMA due to insufficient levels of survival motor neuron (SMN) protein.4 SPINRAZA demonstrated a favorable benefit-risk profile. Thrombocytopenia, renal toxicity and coagulation abnormalities, including acute severe thrombocytopenia, have been observed after administration of other subcutaneously or intravenously administered antisense oligonucleotides. There is a risk of adverse reactions occurring as part of the lumbar puncture procedure (e.g. headache, backpain, vomiting). The timing of SPINRAZA availability in the EU will vary by country, per local reimbursement and access pathways. Biogen has been working with health systems and government agencies across the EU to help patients secure access to SPINRAZA. 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. The EAP has led to the initiation and ongoing treatment of more than 350 eligible individuals with infantile-onset SMA (most likely to develop Type 1) in 17 European countries. Full text:http://newsroom.biogen.com/press-release/investor-relations/spinraza-nusinersen-approved-european-union-first-treatment-spinal-

It is a shock from price for the Spinraza!

Biogen's $375K Spinraza price puts a Sovaldi-style spotlight on rare disease meds

It was big news for Biogen when its spinal muscular atrophy drug Spinraza (nusinersen) won approval just before Christmas. But in the first big drug-price controversy of the new year, the headlines really got going when Biogen unveiled Spinraza’s sticker.

The company set Spinraza’s price at $125,000 per injection, which adds up to $750,000 for the first year of treatment and $375,000 after that. Twitter lit up with critical comments—and messages urging action from lawmakers, including President-elect Donald Trump. Biogen and its development partner Ionis saw their shares drop.

Spinraza’s price isn’t far out of the ballpark in the ultra-orphan drug world, where some treatments top $400,000 per year on a list-price basis. But unfortunately for Biogen, Spinraza has made its debut at a time when public attention on drug prices is at an all-time high.

Unfortunately for other drugmakers that rely on costly rare disease meds, Spinraza’s price could bring some unwelcome attention to the entire field, just as Gilead Sciences’ $84,000 sticker price on its groundbreaking hepatitis C drug Sovaldi did for hep C and beyond. Unfortunately for patients, analysts said, the pricing decision and ensuing backlash is likely to tighten up access to the treatment.

“The sticker-shock presented in the media could turn Spinraza into the Sovaldi of rare disease drugs,” Leerink Partners analyst Geoffrey Porges wrote to investors over the weekend. It could be “the straw that breaks the camel’s back in terms of the U.S. market’s tolerance for rare disease drug pricing.”

As Piper Jaffray analyst Joshua Schimmer pointed out in a Tuesday note, the $375,000 annual cost fits within the realm of ultra-orphan disease therapies such as Alexion’s Soliris, with a list price north of $500,000 per year. In that context, “we think this is quite reasonable, especially considering the high unmet need and meaningful benefit from Spinraza,” Schimmer wrote.

That’s Biogen’s contention as well. The company “carefully considered” the price ahead of launch, spokesman Matt Fearer told CBS News. In the context of its clinical value—and Biogen’s need to fund other R&D—Spinraza’s price “is fairly in line with other therapies for rare orphan diseases,” Fearer said.

Ultra-orphan drugs tend to face much less pricing pressure than their less-expensive counterparts in other fields. That’s because the diseases they treat are so rare, only a few patients need them. The hit to payers’ budgets is relatively small, even compared with much cheaper meds used to treat thousands.

Regardless of how fair or reasonable Spinraza’s sticker might be in the ultra-orphan context, however, the outsize price tag was guaranteed to raise eyebrows, given the close scrutiny drug prices currently face. Most of Twitter’s audience—and most of the general public—doesn’t understand the economics of rare disease drugs.

Therein lies the risk, not just for Biogen and Spinraza, but other rare disease drugs and their makers. Ahead of Spinraza’s approval, Piper Jaffray included a Trump pricing tweet on its list of potential provocative events of the year. “Will Trump feel some sticker shock and rush to his Twitter account?” the analysts wrote Dec. 20. And that’s just what many on Twitter demanded over the weekend. Others tweeted to former presidential candidates Sen. Bernie Sanders and Sen. Marco Rubio, as well as other U.S. lawmakers.

At the very least, the quick pushback on Biogen’s pricing decision is likely to inspire payers to look more closely at Spinraza than they might have otherwise, Porges said. One feature of Spinraza—its standard dosing regardless of body weight—could end up a liability. Many other rare disease doses increase as weight does. And as dosing rises, so does cost, sometimes far beyond the numbers generally reported.

“This inherent price inflation dynamic is one of the ‘undiscussables’ of rare disease that drive pricing well above even the stratospheric ranges that are commonly discussed, frequently debated and occasionally justified for rare diseases,” Porges notes.

Biogen can’t benefit from those dosing-related sales increases, so the company decided to capture the value of its drug in the first-year loading phase, he said. Long term, the cost for Spinraza will be equivalent to, or even less than, that for many other rare disease drugs, but Biogen “will be unable to hide the true price in the back-end through weight-driven price escalation.”

“In turn, patient access is likely to be harmed by this price and its counter-reaction,” he said, “but the decision is ultimately not too out-of-line with other rare disease treatments with life saving, or life extending, potential.”

Information from: http://www.fiercepharma.com/pharma/biogen-s-375k-spinraza-price-puts-a-sovaldi-style-spotlight-rare-disease-meds

In the World has approved a new Drug Treatment for SMA!!!!!!!

Today, unusual day! In the World has approved a new Drug Treatment for SMA!!!!!!!

Today, the FDA announced that it has approved Spinraza (nusinersen) to treat spinal muscular atrophy, making it the first-ever FDA-approved therapy for SMA.

We are thrilled to see our community’s efforts culminate in the approval of Spinraza: not only the first-ever approved treatment for this disease, but also one that addresses the underlying genetic cause of SMA. This has been a story of all groups—families, researchers, companies and the FDA—working together as one community to reach this amazing milestone.

We are especially pleased that the sophisticated and rigorous clinical development plan that Biogen and Ionis chose to implement has resulted in a broad label that will now give so many patients access.

The approval from the FDA for all SMA—pediatric and adult—is the broadest possible label, with no restrictions—and this matches our core value at Cure SMA of being one united community for all ages and all types of SMA.

“Biogen is committed to continuing to work together with the SMA community as we embark on a future where there is now a treatment available for this devastating disease,” said George A. Scangos, PhD, chief executive officer at Biogen. “The teams at Biogen and Ionis are grateful for the support we have received and we join Cure SMA and SMA families in celebrating this critical milestone for the community.”

“There has been a long-standing need for a treatment for spinal muscular atrophy, the most common genetic cause of death in infants, and a disease that can affect people at any stage of life,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “As shown by our suggestion to the sponsor to analyze the results of the study earlier than planned, the FDA is committed to assisting with the development and approval of safe and effective drugs for rare diseases and we worked hard to review this application quickly; we could not be more pleased to have the first approved treatment for this debilitating disease.”

An Historic Moment for the SMA Community

This is an historic moment that our community has been working toward for decades. We extend our deepest gratitude to all our chapters, families, supporters, donors, and partners who have contributed to this milestone.
“This is a landmark day for the SMA community with the first approved drug for the disease. Cure SMA and our entire community have worked together tirelessly for more than thirty years to make this happen. It is important for all of us to stop and celebrate this shared accomplishment that will change and improve the lives of SMA patients,” said Jill Jarecki, PhD, Cure SMA’s Chief Scientific Officer.
Thank You

From 2003 to 2006, Cure SMA provided the very first research funding needed to begin investigation into this therapeutic approach. We thank Drs. Ravindra Singh and Elliot Androphy of the University of Massachusetts Medical School for their work funded by Cure SMA in originally identifying the ISSN1 gene sequence, which is the sequence targeted by Spinraza. We acknowledge Dr. Adrian Krainer and his colleagues at Cold Spring Harbor Laboratory for generating critical intellectual property. All this work was then licensed to Ionis Pharmaceuticals to create the antisense therapy Spinraza. We especially appreciate the team at Ionis for their central role in the rapid advancement of Spinraza.

We are particularly thankful to our partners at Biogen. Together with Ionis, Biogen worked to develop and implement a comprehensive clinical testing program that would provide both the quickest route to approval and the high quality data necessary to support a broad label and access. We thank the families who made many sacrifices to participate in these clinical trials, including the placebo-control groups which were so critical to prove the effectiveness of Spinraza for the whole community.
Finally, we want to recognize the FDA for their partnership with us throughout this process. The FDA understood the critical urgency within our community and acted incredibly quickly to review the robust data submitted in the New Drug Application.
“This first approved treatment provides the greatest hope, and reaffirms the commitment made by the entire community, to create a world without spinal muscular atrophy and rid the world of the suffering wrought by this terrible disease,” said Richard Rubenstein, Chair of the Cure SMA Board of Directors. “It is gratifying to see all of the efforts made by so many people for so many years realized with this breakthrough.”
More About Spinraza

SMA is caused by a mutation in the survival motor neuron gene 1 (SMN1). In a healthy person, this gene produces a protein—called survival motor neuron protein or SMN protein—that is critical to the function of the nerves that control our muscles. Without it, those nerve cells cannot properly function and eventually die, leading to debilitating and often fatal muscle weakness.
All individuals affected by SMA have at least one copy of survival motor neuron gene 2 (SMN2), often referred to as the SMA "backup gene." Due to a splicing error, most of the SMN protein made by SMN2 is missing an important piece, called exon 7. Antisense drugs are small snippets of synthetic genetic material that bind to ribonucleic acid (RNA), so they can be used to fix splicing errors in genes such as SMN2. Spinraza is antisense oligonucleotide that targets SMN2, causing it to make more complete SMN protein.
Spinraza was first known as IONIS-SMNRx, then nusinersen.

Timeline of Events

2003 - 2006: Cure SMA makes $500,000 in seed grants to fund the therapeutic approach that led to Spinraza.

July 2010: Ionis (then known as Isis Pharmaceuticals) licenses the intellectual property to begin development of Spinraza.

December 2011: Ionis initiates a Phase 1 clinical trial of Spinraza.

January 2012: Biogen and Ionis enter into a partnership agreement to continue developing Spinraza.

April 2013: Ionis begins testing Spinraza in Phase 2 clinical trials.

August 2014: Ionis and Biogen launch ENDEAR, a Phase 3 clinical trial testing Spinraza in infants with SMA type I.

November 2014: Ionis and Biogen launch CHERISH, a Phase 3 clinical trial testing Spinraza in children with SMA type II.

March 2015: Biogen and Ionis launch NURTURE, a Phase 2 clinical trial testing Spinraza in infants genetically diagnosed with SMA but not yet showing symptoms.

August 12, 2016: Biogen and Ionis announce their intention to initiate regulatory filings for Spinraza, after the drug meets its primary endpoint in an interim analysis of ENDEAR.

September 26, 2016: Biogen and Ionis announce that they have completed their rolling NDA submission to the FDA and EMA.

October 28, 2016: Biogen and Ionis announce that the FDA has accepted their New Drug Application with priority review.

November 7, 2016: Biogen and Ionis announce that SPINRAZA also met its primary endpoint in an interim analysis of CHERISH.

December 23, 2016. The FDA approves Spinraza for SMA.

Text from; http://www.curesma.org/news/spinraza-approved.html

Biogen Completes Rolling Submission of New Drug Application to FDA

I AM HAPPY TODAY FROM THIS NEWS!

Biogen and Ionis today announced that Biogen has completed the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the approval of nusinersen, an investigational treatment for spinal muscular atrophy (SMA). Biogen has also applied for Priority Review which, if granted, would shorten the review period of nusinersen following the Agency’s acceptance of the NDA.

“Since announcing the positive results of the ENDEAR interim analysis in infantile-onset SMA last month, we have heard from many families expressing their excitement about nusinersen. Their stories continue to inspire us and they are in the forefront of our minds as we work to support the FDA’s review of nusinersen,” noted Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “We appreciate the FDA’s collaboration with us during the application process, and we look forward to continuing this productive dialogue, with the goal of rapidly bringing the first treatment for SMA to as many patients as possible.”

In addition to the NDA filing with FDA, Biogen plans to submit a Marketing Authorization Application (MAA) for nusinersen to the European Medicines Agency (EMA) in the coming weeks. The EMA’s Committee for Medicinal Products for Human Use (CHMP) recently granted Accelerated Assessment to nusinersen, which can reduce the standard review time. Biogen will initiate regulatory filings in other countries in the coming months.

NEXT:http://www.curesma.org/news/biogen-completes-nda-submission.html

5 Experimental SMA Therapies You Might Find Interesting

1. AVXS 101

Recently, AveXis’ gene therapy candidate AVXS-101, the only gene therapy for spinal muscular atrophy currently in human testing, has been granted FDA orphan drug status for treatment of all types of SMA. It was also granted FDA breakthrough therapy designation and was fast track designation.


2. CK-2127107 (CK-107)

In collaboration with Astellas, Cytokinetics is developing CK-2127107 (CK-107), a new skeletal muscle troponin activator as a potential treatment for people living with SMA. CK-107 has completed five Phase 1 clinical trials in healthy volunteers, and is currently the subject of two Phase 2 clinical trials.


3. Nusinersen

Biogen and Ionis Pharmaceuticals recently announced that nusinersen, their investigational drug for treating SMA, met the primary end point for the interim analysis of the ENDEAR Phase 3 trial evaluating nusinersen in infantile-onset SMA.


4. RG7800

PTC’s more developed SMA drug candidate, RG7800, is the subject of a Phase 2 trial in adult and pediatric SMA patients, but dosing was suspended and the trial was placed on clinical hold to investigate a non-clinical safety finding observed in a longer-term animal study.


5. Gene Therapy

Learn more about how gene therapy can be used to treat SMA:http://smanewstoday.com/tag/gene-therapy/

http://smanewstoday.com/social-clips/2016/09/06/5-sma-experimental-therapies-you-should-know-about/5/

Expanded Access Program for Nusinersen in Participants for SMA 1 type

In soon time we wait for a miracle drug for SMA

Biogen is working to open a global expanded access program (EAP) for eligible patients with infantile-onset SMA (consistent with Type 1) in the coming months. The EAP can be initiated at existing nusinersen clinical trial sites in countries where EAPs are permitted according to local laws and regulations, can be operationalized, and where there is a path that can support long-term availability of nusinersen. Once the EAP is operational and required local approvals are in place, individual participating sites may start enrollment after they have transitioned ENDEAR study participants to the open-label extension study.

More information on the EAP can be found on the clinicaltrials.gov website under the NCT identifier NCT02865109 https://clinicaltrials.gov/ct2/show/NCT02865109

Full text: http://www.curesma.org/news/important-milestone-reached.html

Biogen and Ionis Pharmaceuticals Report Nusinersen Meets Primary Endpoint at Interim Analysis of Phase 3 ENDEAR Study in Infantile-Onset Spinal Muscular Atrophy

CAMBRIDGE, Mass. & CARLSBAD, Calif.--(BUSINESS WIRE)--Biogen (NASDAQ:BIIB) and Ionis Pharmaceuticals (NASDAQ:IONS) today announced that nusinersen, their investigational treatment for spinal muscular atrophy (SMA), met the primary endpoint pre-specified for the interim analysis of ENDEAR, the Phase 3 trial evaluating nusinersen in infantile-onset (consistent with Type 1) SMA. The analysis found that infants receiving nusinersen experienced a statistically significant improvement in the achievement of motor milestones compared to those who did not receive treatment. Nusinersen demonstrated an acceptable safety profile in the trial. As a result of these findings, Biogen has exercised its option to develop and commercialize nusinersen globally and paid Ionis a $75 million license fee. Biogen will initiate regulatory filings globally in the coming months.

“We are grateful to the families participating in the clinical trials, who continue to inspire us. We want to thank them, along with the investigators who have worked tirelessly on this program and the broader SMA community, for their partnership. Without their contributions, we would not be here today,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “We share the community’s sense of urgency as we strive to bring the first treatment for SMA, the leading genetic cause of infant mortality, to families facing this devastating disease. We remain committed to understanding the potential of nusinersen in the broader SMA population and will continue to focus on the rapid completion of our ongoing studies.”

Based on the results of the pre-specified interim analysis, the ENDEAR study will be stopped and participants will be able to transition into the SHINE open-label study in which all patients receive nusinersen. Data from the other endpoints of ENDEAR will be analyzed when the full data set is available. Results will be presented at future medical congresses. Additionally, participants enrolled in the sham-controlled arm of EMBRACE, a Phase 2 study which also included infantile-onset patients, will have the opportunity to receive nusinersen.

The other studies in the nusinersen program, including CHERISH (later-onset consistent with Type 2) and NURTURE (pre-symptomatic infants), will continue as planned in order to collect the data to demonstrate the safety and efficacy of nusinersen in these populations.

“We are hopeful that nusinersen, if approved, will make a meaningful difference in the lives of patients and families affected by SMA. We look forward to working with Biogen on completing the clinical program and preparing for what we hope is a positive regulatory review,” said B. Lynne Parshall, chief operating officer at Ionis Pharmaceuticals. “Nusinersen is the first antisense drug from our neurological disease franchise to advance to regulatory review, and it illustrates the potential of our antisense technology to address severe diseases that other therapeutic modalities are unable to address adequately.”

Biogen is working to open a global expanded access program (EAP) for eligible patients with infantile-onset SMA (consistent with Type 1) in the coming months. The EAP can be initiated at existing nusinersen clinical trial sites in countries where EAPs are permitted according to local laws and regulations, can be operationalized, and where there is a path that can support long-term availability of nusinersen. Once the EAP is operational and required local approvals are in place, individual participating sites may start enrollment after they have transitioned ENDEAR study participants to the open-label extension study.

“Today is a hopeful day for the SMA community, which has worked tirelessly to support research and development for this terrible disease. Many of our families have participated in this and other clinical trials in order to advance our understanding of SMA. We are excited about reaching this important milestone, and the opportunity these results create to potentially bring the first treatment option for SMA to patients and families. We will continue to relentlessly support research into SMA until we have therapies for all and, ultimately, a cure,” commented Kenneth Hobby, President, Cure SMA.

Biogen is now responsible for all nusinersen development, regulatory and commercialization activities and costs. Ionis will complete the Phase 3 studies and work with Biogen on regulatory filings. The two companies will also work together to transition the clinical programs that Ionis is conducting to Biogen. Ionis is eligible to receive tiered royalties on any potential sales of nusineren up to a percentage in the mid-teens, in addition to up to $150 million in milestone payments based on regulatory approvals.

Webcast

The companies will host a live webcast to discuss the results of the Phase 3 ENDEAR interim results for nusinersen today, August 1, 2016, from 9:00 to 9:30 a.m. EDT. Participants may access the webcast through the Investors section of www.biogen.com or www.ionispharma.com. Following the live webcast, an archived version of the call will be available at the same URLs for one month.

The Nusinersen Clinical Trial Program

The nusinersen Phase 3 program is comprised of two registrational studies, ENDEAR and CHERISH. ENDEAR is a thirteen-month study investigating nusinersen in 122 patients with infantile-onset SMA; the onset of signs and symptoms of SMA less than or equal to 6 months and age less than or equal to 7 months at screening. Based on insights gained from earlier-stage studies and discussions with regulators, a primary endpoint was added to ENDEAR earlier this year that evaluates the proportion of motor milestone responders from the motor component of the Hammersmith Infant Neurological Examination (HINE).

CHERISH is a fifteen-month study investigating nusinersen in 126 non-ambulatory patients with later-onset SMA; onset of signs and symptoms greater than 6 months and age 2 to 12 years at screening. CHERISH was fully enrolled in May 2016.

Additionally, the SHINE open-label extension study for patients who previously participated in ENDEAR and CHERISH is open and is intended to evaluate the long-term safety and tolerability of nusinersen.

Two additional Phase 2 studies, EMBRACE and NURTURE, were designed to collect additional data on nusinersen. The EMBRACE study is designed to collect additional data on a small subset of patients with infantile or later-onset SMA who do not meet the age and other criteria of ENDEAR or CHERISH. NURTURE is an ongoing study in pre-symptomatic infants who are less than or equal to 6 weeks of age at time of first dose to determine if treatment before symptoms begin would prevent or delay the onset of SMA symptoms. All studies are being conducted on a global scale.

About SMA 1-5

Spinal Muscular Atrophy (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 most severe life-threatening form, produce very little SMN protein and do not achieve the ability to sit without support or live beyond 2 years without respiratory support. People with Type 2 and Type 3 produce greater amounts of SMN protein and have less severe, but still life-altering forms of SMA.

Currently, there is no approved treatment for SMA.

About Nusinersen

Nusinersen is an investigational, potentially disease-modifying therapy6 for the treatment of SMA. Nusinersen is an antisense oligonucleotide (ASO) that is designed to alter the splicing of SMN2, a gene that is nearly identical to SMN1, in order to increase production of fully functional SMN protein. 7

ASOs are short synthetic strings of nucleotides designed to selectively bind to target RNA and regulate gene expression. Through use of this technology, nusinersen has the potential to increase the amount of functional SMN protein in infants and children with SMA.

Both the U.S. and EU regulatory agencies have granted special status to nusinersen in an effort to expedite the review process, including Orphan Drug Status and Fast Track Designation in the U.S. and Orphan Drug Designation in the EU.

We acknowledge support from the following organizations for nusinersen: Muscular Dystrophy Association, SMA Foundation, Cure SMA and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School.

About Biogen

Through cutting-edge science and medicine, Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological, autoimmune and rare diseases. Founded in 1978, Biogen is one of the world’s oldest independent biotechnology companies and patients worldwide benefit from its leading multiple sclerosis and innovative hemophilia therapies. For more information, please visit www.biogen.com. Follow us on Twitter.

About Ionis Pharmaceuticals Inc.

Ionis is the leading company in RNA-targeted drug discovery and development focused on developing drugs for patients who have the highest unmet medical needs, such as those patients with severe and rare diseases. Using its proprietary antisense technology, Ionis has created a large pipeline of first-in-class or best-in-class drugs, with over a dozen drugs in mid- to late-stage development. Drugs currently in Phase 3 development include volanesorsen, a drug Ionis is developing and plans to commercialize through its wholly owned subsidiary, Akcea Therapeutics, to treat patients with either familial chylomicronemia syndrome or familial partial lipodystrophy; IONIS-TTRRx, a drug Ionis is developing with GSK to treat patients with all forms of TTR amyloidosis; and nusinersen, a drug Ionis is developing with Biogen to treat infants and children with spinal muscular atrophy. Ionis' patents provide strong and extensive protection for its drugs and technology. Additional information about Ionis is available at www.ionispharma.com.

Biogen Safe Harbor

This press release contains forward-looking statements, including statements relating to the safety and efficacy of nusinersen, as well as clinical trial results and plans, potential regulatory filings and expected timelines, including expanded access for nusinersen, including the transition of the ENDEAR and EMBRACE clinical trial study participants to an open label study and the timing thereof, the submission of applications to regulatory authorities and the timing thereof, and the opening of an EAP and the timing thereof. These statements may be identified by words such as "believe," "expect," "may," "plan," "potential," "will" and similar expressions, and are based on our current beliefs and expectations. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Factors which could cause actual results to differ materially from our current expectations include the actual timing and content of submissions to and decisions made by the regulatory authorities regarding marketing authorization applications for nusinersen, the actual timing and final results of the nusinersen clinical trials and the uncertainties involved in operationalizing an EAP. For more detailed information on the risks and uncertainties associated with our drug development and commercialization activities, please review the Risk Factors section of our most recent annual or quarterly report filed with the Securities and Exchange Commission. Any forward-looking statements speak only as of the date of this press release and we assume no obligation to update any forward-looking statement.

Ionis Forward-looking Statement

This press release includes forward-looking statements regarding Ionis' strategic relationship with Biogen and the development, activity, therapeutic potential, safety and commercialization of nusinersen. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’ programs are described in additional detail in Ionis’ annual report on Form 10-K for the year ended December 31, 2015, and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.

BIOGEN and the BIOGEN logo are registered trademarks of BIOGEN.

Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics™ is a trademark of Ionis Pharmaceuticals, Inc.

http://media.biogen.com/press-release/investor-relations/biogen-and-ionis-pharmaceuticals-report-nusinersen-meets-primary-en

Biogen and Ionis Release Spring 2016 Community Update

Biogen and Ionis Pharmaceuticals recently provided an update on the clinical development of nusinersen (IONIS-SMNRx), which is currently being tested in Phase 3 clinical trials:

As we approach the upcoming Cure SMA conference in Anaheim, we want to provide an update on the status of the nusinersen program and its direction.

Enrollment is now completed in both of our Phase 3 studies, CHERISH (childhood-onset) and ENDEAR (infant-onset), as well as our Phase 2 EMBRACE study. These are important milestones for the nusinersen program and both Phase 3 studies remain on track to complete in the first half of 2017.

The open-label SHINE study remains open for patients who have completed participation in ENDEAR and CHERISH, as well as patients who have completed the open-label Phase 2 study in childhood-onset SMA patients.

Ionis recently presented additional data from the open-label Phase 2 study in infants at the American Academy of Neurology Meeting. While we continue to be optimistic about these data, our well-controlled Phase 3 studies (CHERISH and ENDEAR) are designed to provide the data necessary for regulatory review and approval.

Additionally, the primary and secondary endpoints in our ENDEAR clinical trial protocol were recently updated. The decision to change the endpoints was carefully made based on additional insight from our open-label studies and discussions with regulators and experts in the field over the last year. The ENDEAR study was initially designed with a primary endpoint of permanent ventilation-free survival, meaning we would observe patients treated with 13 months of nusinersen compared to untreated patients and evaluate the number of patients who survive without the need for permanent ventilation between the two groups. It became increasingly clear that measuring motor milestones, endpoints of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders ("CHOP INTEND") and Compound Muscle Action Potential (CMAP), could be useful indicators of nusinersen’s potential efficacy in the ENDEAR study. Therefore, study’s primary endpoint has now been changed to add a second primary endpoint: motor milestones.

Full text: http://www.curesma.org/news/biogen-ionis-spring-2016-update.html