Biogen and Ionis Pharmaceuticals Provide Important Update on First Ever SMA Regulatory Filings

By Cure SMA | Published On August 1, 2016

Today, Biogen and Ionis Pharmaceuticals provided a statement regarding the decision to submit the first ever SMA regulatory filings for FDA approval.

Dear Members of the SMA Community,

Today marks an important day in our collective pursuit of a meaningful treatment for Spinal Muscular Atrophy (SMA). We are pleased to share the exciting news that we have reported positive results from a pre-specified interim analysis of the ENDEAR study in infants with Spinal Muscular Atrophy (SMA). As a result, plans are underway to transition all ENDEAR study participants to nusinersen in an open-label extension study and close the ENDEAR study. We plan to submit regulatory filings globally in the coming months. This step will hopefully bring us closer to our ultimate goal of making nusinersen available as quickly as possible as an approved therapy.

We would not be here without the support of the families participating in our clinical studies, the study doctors who provide exceptional care for these families, and the entire SMA community, who inspire us to be at our best each and every day. Thank you for your contributions which have brought us to this meaningful moment.

As we look to the future we want to share additional perspective on where we are today and where we are headed in the coming months:

  • Based on the severity of the disease and urgent need in SMA, we designed the ENDEAR protocol to include an option for an interim analysis prior to the formal conclusion of the trial.
  • We conducted detailed scientific analyses using all of the available data to identify the earliest point in the study when the interim analysis could be conducted to provide regulators with the well-controlled data needed to assess the safety and efficacy of nusinersen.
  • Because of the positive results of the interim analysis in the infantile-onset (consistent with Type 1) SMA population, all ENDEAR and EMBRACE study participants can elect to receive nusinersen by transitioning to the extension studies.
  • Biogen is working to open an expanded access program (EAP) in the fall to make nusinersen available for eligible patients with infantile-onset SMA (consistent with Type 1) based on the unmet medical need in SMA and positive ENDEAR interim results.

Over the coming months we will work to submit our marketing applications to regulatory authorities in the U.S. and EU, with additional countries to follow. The marketing applications will include the ENDEAR interim analysis and all other clinical and preclinical data currently available. We are continuing to explore expedited review options with regulatory agencies, but we do not have specific timelines for review and potential approval. Regulatory review varies by country; in general standard review in the U.S. is 10 months once a new drug application is accepted, and review time averages between 13-15 months in the EU. This amount of time can vary greatly and can impact the timing to product availability. We will continue our additional studies in the nusinersen program, including CHERISH (later-onset consistent with Type 2), NURTURE (pre-symptomatic infants), and the ongoing Phase 2 open label studies (CS3a and CS12), in order to continue to collect the data to demonstrate the safety and efficacy of nusinersen in these populations.

In light of these regulatory review timelines, Biogen is working to open an expanded access program (EAP) in the fall of 2016, which will provide access to patients with infantile onset SMA (consistent with Type 1) prior to potential regulatory approval.

  • Existing clinical trial sites, because of their experience in administering nusinersen, can participate in the EAP in countries where EAPs are permitted according to local laws and regulations and can be operationalized, and where there is a path that can support long-term availability of nusinersen.
  • Once the EAP is open, 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.
  • Eligibility criteria and additional details on the infantile-onset (consistent with Type 1) EAP will be posted on clinicaltrials.gov in the coming weeks. This site will be the best place for you and your physician to obtain the most up to date information on the program.

We understand this EAP will not meet the needs of the entire SMA community. We intend to open an EAP in the later-onset (consistent with Type 2) population in the future, if and when we have collected enough positive well-controlled data to enable regulators to assess the safety and efficacy of nusinersen in this population and we are able to close the CHERISH sham-controlled study. We are working to complete our CHERISH study as quickly as possible and continue to explore all opportunities to shorten the timeline to review and potential approval.

Our respect and admiration for the SMA community’s tireless efforts to advance SMA research and development for an approved treatment grows each and every day. We still have work to do, but this milestone advances us to the next steps in this endeavor. We will continue to share information and program updates to the community when possible and would like to express our deepest appreciation to all involved in this important journey.

Biogen and Ionis Pharmaceuticals

Community FAQs Regarding this Update

On August 1, 2016 Biogen and Ionis Pharmaceuticals announced that nusinersen, our investigational treatment for Spinal Muscular Atrophy (SMA), met the primary endpoint pre-specified for the interim analysis of ENDEAR, the Phase 3 clinical trial evaluating nusinersen in infantile-onset (consistent with Type 1) SMA.

We recognize this exciting program milestone may bring certain questions to mind. Below we hope you’ll find answers to some of these questions. If you need additional information, please feel free to contact Biogen’s Patient Center at patientcenter@biogen.com.

1. What is the ENDEAR study?

The ENDEAR study was originally designed to be a 13-month clinical trial including approximately 110 patients with infantile-onset (consistent with Type 1) SMA. The purpose of the trial was to collect well-controlled data for regulators to assess the safety and efficacy of nusinersen in this patient population. Initially, the study was designed with a primary endpoint of ventilation-free survival. As we gained more insight from our open-label studies, it became increasingly clear that measuring motor milestones could be a useful indicator of nusinersen’s potential efficacy in the ENDEAR study. As such, the primary and secondary endpoints were updated in May of 2016.

2. Why did you conduct an interim analysis? What does this mean?

When designing the ENDEAR study, we consulted extensively with regulators, experts in field and members of the community to design a protocol that would allow us to collect the necessary well-controlled data in the shortest time possible.

We designed the ENDEAR protocol to include an option for an interim analysis prior to the formal conclusion of the trial in order to evaluate if a significant treatment effect was detectable ahead of the full data collection. The interim analysis has showed that infants taking nusinersen experienced a statistically significant improvement in the achievement of motor milestones compared to those who did not receive treatment.

Because of the positive results of the interim analysis in the infantile-onset (consistent with Type 1) SMA population, all ENDEAR and EMBRACE study participants can elect to receive nusinersen by enrolling in the extension studies.

3. What happens next?

We will continue to collect data on all of the participants enrolled in the clinical trial through their next office visit as we work to submit our regulatory filings. The regulatory filings will include the ENDEAR interim analysis data and all other clinical and preclinical data currently available. We anticipate we will be able to submit our marketing applications to both the FDA and the EMA in the coming months, with filings in other countries to follow.

4. When will nusinersen be approved?

Once the filing packages are submitted, they must be accepted or validated by each regulatory agency before the review period starts. In the U.S., companies are notified of an acceptance 60 days after submission. In the EU, companies are notified that the submission has been validated approximately 30 days after submission. Once accepted or validated, the review periods start.

We are exploring expedited review options with both agencies and do not yet have a specific timeline for review and potential approval of nusinersen in either region. Review and approval varies by country, but, in general once accepted or validated, standard review in the U.S. is 10 months and review time averages between 13-15 months in the EU.

5. What are your plans for the CHERISH study? Will you conduct an interim analysis with this trial, too?

Based on our ongoing conversations with regulators, data from a well-controlled study in later-onset (consistent with Type 2) SMA will be needed in order for them to assess the safety and efficacy of nusinersen in this population. Once we are able to collect enough well-controlled data to have a pathway to approval in that population, and we are able to end the CHERISH sham-controlled study arm, we will be able to make a determination about how to proceed.

We are working to complete our CHERISH studies as quickly as possible and continue to explore all opportunities to shorten the timeline to review and potential approval.

6. Are you opening an Expanded Access Program (EAP)?

Given the positive data from the interim analysis, Biogen is working to open an expanded access program (EAP) for eligible patients with infantile-onset SMA (consistent with Type 1). We hope this program will mark the initial phase in our effort to enable expanded access to nusinersen for patients with SMA.

Existing clinical trial sites, because of their experience in administering nusinersen, can participate in the EAP in countries where EAPs are permitted according to local laws and regulations, can be operationalized and there is a path that can support long-term availability of nusinersen. Once the EAP is open 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.

7. How can I find out if I am or my child is eligible for the EAP?

In the coming weeks, eligibility criteria and additional details on the infantile-onset (consistent with Type 1) EAP will be posted on clinicaltrials.gov. This will be the best place for you and your physician to obtain the most up-to-date information on the program.

To participate in the EAP, physicians at eligible clinical trial sites must make a formal request on behalf of the patient to Biogen or to Idis, Biogen’s partner company running the EAP program. The requesting physician is responsible for the patient’s care and all legal and regulatory requirements for medically monitoring the patient while that patient is receiving the investigational therapy.

We understand the EAP will not meet the needs of the entire SMA community. We intend to open an EAP for later-onset SMA (consistent with Type 2) in the future, if and when we are able to collect enough well-controlled data to enable regulators to assess the safety and efficacy in nusinersen in this population and we are able to close the CHERISH sham-controlled study.

8. Will you charge for the EAP?

Biogen will supply nusinersen free of charge for the period in which patients are being treated under the expanded access program. Any other healthcare related costs are not covered under the EAP.

9. How will we find out more information about what’s happening next?

The interim analysis represents an important milestone for the program, but we still have work to do as we move towards our number one goal of advancing nusinersen toward approval. We are committed to open and transparent communications with the SMA community whenever possible and will continue to update the community as the program progresses.

Topics: Clinical Trials, Front Page News

© 2018 Cure SMA | Privacy Policy

Powered by Blackbaud
nonprofit software