How do patients get access to treatment?

Before you begin: review guidance for submission

Guidance for geneticistsGuidance for healthcare providersGuidance for patients or guardians

Guidance for geneticists

Detailed understanding of the genetics of the patient is critical to determining whether ASO technology is appropriate for a patient. As a general rule, full genome sequencing is most informative and needed. Below are a few tips to assure that the necessary information is available to support as rapid and thoughtful a decision as possible.

  • Patient must live in the United States.
  • Patient’s genetic mutation or change in gene function must be ultra-rare, meaning it affects approximately n1-10 patients in the world.
  • Provide diagnosis.
  • Provide the official name and symbol of the affected gene as defined by Gen Bank Accession Number and Gene ID.
  • Define the nature of the genetic change (gain of function, loss of function, splicing defect).
  • Define other genes that are altered.
  • Characterize why this genetic change is unique compared to more common genetic changes associated with the diagnosis.
  • Provide available information on gene(s) function.

Strengths and limitations of ASO technology

ASO technology is validated, versatile (multiple post-RNA binding mechanisms), effective in many organs at low doses, deliverable by many routes of administration, and active both systemically and locally, e.g. aerosol for lung disease, intrathecal for neurological diseases.  Moreover, ASO medicines of each specific chemical class behave similarly, facilitating dose and schedule selection.

However, as is the case for all drug discovery technologies, ASO technology has limits. ASO technology cannot replace genes, therefore, true null mutations may be better treated with gene therapy. Compound heterozygous mutations are unlikely to be treatable by ASOs, or if the gene in question serves a vital function, then reducing the transcript from that gene may be too risky.

IF YOU HAVE QUESTIONS PLEASE CONTACT n-LOREM BEFORE SUBMITTING THE PROPOSAL FOR TREATMENT FORM.

Guidance for healthcare providers

For a patient to be considered for treatment with an experimental ASO several essential elements must be in place:

  • Patient must live in the United States.
  • Patient’s genetic mutation or change in gene function must be ultra-rare, meaning it affects approximately n1-10 patients in the world.
  • The patient must have a diagnosis and full genomic analysis.
  • The type of change in genetic function must be understood.
  • An experienced investigator with the knowledge and experience to submit and manage an investigator-initiated IND must be available.
  • A tertiary care center experienced and capable of expeditiously supporting an investigator-initiated IND must be in place.
  • The mutation, or change in gene function, must be unique, i.e. ~1-10 patients are known to have the specific mutation. n-Lorem has been established to consider providing experimental antisense oligonucleotides (ASOs) treatments for genetically defined diseases that are known to occur in 1-10 patients in the world.

ASO technology is versatile and broadly useful but has limits. Please be aware of the limits of the technology.

Strengths and limitations of ASO technology

ASO technology is validated, versatile (multiple post-RNA binding mechanisms), effective in many organs at low doses, deliverable by many routes of administration, and active both systemically and locally, e.g. aerosol for lung disease, intrathecal for neurological diseases.  Moreover, ASO medicines of each specific chemical class behave similarly, facilitating dose and schedule selection.

However, as is the case for all drug discovery technologies, ASO technology has limits. ASO technology cannot replace genes, therefore, true null mutations may be better treated with gene therapy. Compound heterozygous mutations are unlikely to be treatable by ASOs, or if the gene in question serves a vital function, then reducing the transcript from that gene may be too risky.

IF YOU HAVE QUESTIONS PLEASE CONTACT n-LOREM BEFORE SUBMITTING THE PROPOSAL FOR TREATMENT FORM.

Guidance for patients or guardians

To qualify for treatment with an experimental ASO, you must have a diagnosis, the genetic cause must be defined, and the patient must be cared for by an investigator and related institution experienced in managing investigator-initiated INDs. Therefore, we recommend:

  • Patient must live in the United States.
  • Patient’s genetic mutation or change in gene function must be ultra-rare, meaning it affects approximately n1-10 patients in the world.
  • Work closely with your physician, geneticist and institution.
  • Consider working with investigators in the Undiagnosed Disease Network if any of the above elements are unavailable to you.
  • Understand that ASO technology, like all drug discovery technologies, has limits and we may not be able to help every patient.

IF YOU HAVE QUESTIONS, PLEASE CONTACT n-LOREM BEFORE SUBMITTING THE PROPOSAL FOR TREATMENT FORM.


Step 1: Seek a diagnosis

The first step toward potential treatment is to achieve a diagnosis and full genetic analysis. If the patient/caregiver or institution is unable to achieve a diagnosis and perform a full genetic analysis, patients and/or their caregivers should contact physicians and institutions capable of achieving these essential goals. n-Lorem recommends contacting the Undiagnosed Diseases Network (UDN) at https://undiagnosed.hms.harvard.edu/ or 1-844-RING-UDN (1-844-746-4836) or similar organization. The UDN is a consortium of physicians and institutions focused on using modern genetic methods to characterize difficult to diagnose patients.

Step 2: Work with physician to submit a Proposal For Treatment Form

Work with a physician to complete a Proposal For Treatment form. The form is sent directly to n-Lorem who will make an informed decision about whether a patient is appropriate to receive an experimental ASO treatment, substantial information concerning the patient and the genetics of the patient must be provided. Additionally, it is critical that the patient be cared for by a qualified investigator and a qualified institution.

Step 3: Proposal For Treatment Form is reviewed by the Access to Treatment Committee

Our Access to Treatment Committee is made up of physicians, geneticists, experts in conducting clinical trials, experts in ASO technology, bioethicists, and patient advocates. This committee reviews proposals from physicians and patients to treat diagnosed, genetically confirmed ultra-rare disease patients. Learn more

Step 4: Access to Treatment Committee makes recommendation to n-Lorem

Upon completed review, the Access to Treatment Committee makes recommendations to the n-Lorem’s executive team with regard to the appropriateness to treat. At the Foundation we understand that there are seriously ill patients with immediate needs of a treatment for their condition. We are sympathetic to patients and all who are involved. We plan to do all we can to make sure we are as transparent as possible. Due to the complex nature of treating patients with ultra-rare diseases, unfortunately, not all can be approved for treatment.

Step 5: n-Lorem determines whether a patient is to be treated with ASO

Proposals are approved and prioritized based on criteria such as: the severity of the disease, feasibility of developing an ASO treatment for the genetic cause of the disease, degree of potential benefit vs. potential risks, practicality of treatment, availability of physician and institution to treat patient and conduct necessary studies, and other complexities of the condition.

Step 6: n-Lorem notifies submitter of treatment decision

n-Lorem notifies all submitters of treatment decisions.

Step 7: If a patient’s proposal for treatment is accepted

The n-Lorem foundation works with Ionis, the leader in RNA-targeted therapeutics, to:

  • Develop a personalized precision experimental ASO medicine
  • Perform studies to evaluate the efficacy and safety of experimental ASO medicine candidates and choose the best one for treatment
  • Work with clinical investigators to generate and submit an Investigational New Drug (IND) application to the Institutional Review Board and the Regulatory authorities

Step 8: Obtain regulatory permission to treat

n-Lorem works with clinical investigator to obtain regulatory approval to treat. Upon regulatory permission, an investigator-led clinical trial is initiated and then a patient may receive their custom experimental ASO treatment at no cost.