Providing Access to AVM0703

Compassionate Use/Expanded Access Program Description

Providing access to care, serving overlooked populations, and working to save lives is at the core of AVM Biotechnology’s mission. Compassionate Use, also referred to as “Expanded Access” programs, are designed to make investigational medical products available as early as possible to patients without therapeutic options, because they have exhausted or are not a good candidate for approved therapies and cannot enter a clinical trial.

The Compassionate Use Program with AVM0703 is no exception and is intended to provide access to AVM0703 for patients with serious or immediately life-threatening diseases or conditions who lack other therapeutic options and may benefit from it.

Please note that investigational medicinal products have not yet received regulatory approval; thus, their potential risks and benefits are not yet established. Physicians and patients should consider all possible benefits and risks when seeking access to an investigational drug.

Physician Instructions

Thank you for inquiring about a Compassionate Use/Expanded Access Program through AVM Biotechnology. This information is provided to help guide you through the process, to make it as easy as possible and ensure compliance with the regulatory agencies.

Prior to starting the process, please keep the following in mind:

As the requesting physician you are both the sponsor and principal investigator and you must apply to the FDA for a Single-Patient, Physician Sponsored Investigational New Drug number (IND). While it may sound intimidating, AVM can assist in preparing the application to make the process as easy as possible.

Your request must meet all of the following criteria to qualify as described in 21 CFR 56.102(d):

• The patient is in a life-threatening condition that needs immediate treatment.
• No generally acceptable alternative for treating the patient is available.
• Because of the immediate need to use the drug, there is no time to use existing procedures to get FDA approval for the use.

The application process consists of the following steps:

1. Complete the Compassionate Use Application and download the Non-Disclosure and Confidentiality Agreement.

If the above criteria are met, you can seek access to AVM0703 from AVM Biotechnology by completing a Compassionate Use Application and download the Non-Disclosure and Confidentiality Agreement.

Sign these documents (either wet signature or electronically) and email both signed documents to: compassionateuse@avmbiotech.com or fax them to 206.424.8701.

Once the signed Non-Disclosure and Confidentiality Agreement has been received, you will be provided with the study documents, e.g., Protocol, Sample Collection Requests, Informed Consent Template (IC), Investigator’s Brochure, (IB), Pharmacy Manual.

2. Contact Dr. Ed Loniewski, AVM Chief Medical Officer (eloniewski@avmbiotech.com).
Once the information from #1 above is received, he will provide additional information (e.g., Protocol, IB, IC, FDA form 3926, Pharmacy Manual, etc.) for the application. AVM Biotechnology provides regulatory templates free of charge for FDA approved Compassionate Use/Expanded Access applications, which make the submission process to the FDA straightforward. The FDA has provided instructions on how to complete form 3926.

You can request emergency use from the FDA by checking the box “Alternative IRB Review” on form 3926, however, you must still have an expedited review by the Institutional Review Board (IRB) chairperson as soon as possible. If you do not have access to an IRB, your application can be expedited through a third-party IRB. For this purpose, AVM Biotechnology has arranged for The Western Institutional Review Board (WIRB) to serve as the IRB for each request at no cost.

Please note this on the application form, the emergency use provision is an exemption from prospective review and approval by the IRB. The exemption, which may not be used unless all conditions described in 21 CFR 56.102(d) exist, allows for one emergency use of a study drug.

3. Contact the FDA for a Single-Patient compassionate use Investigational New Drug (IND) number.
Use this IND number on all correspondence. The Division of Hematological Malignancies II (HMD2) is currently the group within the FDA that handles these requests for AVM0703.

E-mail: ONCProjectFacilitate@fda.hhs.gov
Phone: 301-796-7550
Fax: 301-796-9845
Address:

Food and Drug Administration
Center for Drug Evaluation and Research, Division of Hematologic Malignancies 2 (DHM2),
5901-B Ammendale Road
Beltsville, MD 20705-1266

If you cannot get through using the above contact info, use the alternative FDA contact information below:

Phone numbers: 301-796-3400 or 855-543-3784
Fax: 301-431-6353
E-mail: druginfo@fda.hhs.gov

More information on this step of the process can be found on the FDA website.

4. Request a Letter of Authorization (LOA) from AVM Biotechnology.
This can normally be sent within 24 hours of the request. You will need to include this with your FDA 3926 form.

5. Submit the documentation to WIRB or local IRB for review.

6. Submit the documentation to the FDA and send an electronic copy to AVM Biotechnology.

√     Completed FDA Form 3926, including the physician’s CV

√     Protocol

√     IRB approval with the approved Informed Consent (IC)

√     Letter of Authorization (LOA)

For help or questions, please contact AVM Chief Medical Officer, Dr. Ed Loniewski (eloniewski@avmbiotech.com).

7. Provide an electronic copy of the FDA approval letter to AVM Biotechnology and address for drug shipment.
Please allow up to 2 business days from the time of approved IND to the delivery of the drug to your institution or practice. The cost of this medication is provided free of charge under the Compassionate Use Program. AVM Biotechnology will provide you and/or your staff with a tracking number to ensure the drug is delivered prior to the scheduled treatment date. The date and place of the treatment as well as information on the key contact people involved in the treatment should be provided in the initial application.

Adverse Event Reporting and Other Obligations
As the IND Sponsor and Principle Investigator, you are required to report any adverse events to the FDA as well as using FDA Form 3500A together with Form 1571). Please also send a copy to AVM Chief Medical Officer, Dr. Ed Loniewski (eloniewski@avmbiotech.com). You are required to report the outcome of the treatment to the FDA and your IRB. If the treatment lasts over 12 months, you must submit an annual report.

AVM Biotechnology is proud to provide 24/7 support for compassionate use treatment with AVM0703 to all sponsoring physicians. Help and assistance with any questions, including dosing, potential side effects and the potential methods to prevent and or treat those side effects, is always available.

Additional Resources

Reagan Udall Foundation has an Expanded Access Navigator to assist you. Additional instructions can also be found here on the FDA website.

Patient / Family Instructions

Accessing the AVM Biotechnology Compassionate Use Program is straightforward. Patients and their families, however, may not directly request the use of AVM0703 for compassionate use from the FDA. The request needs to be initiated by the physician. Patients and families can play a role, by encouraging the physician to work with AVM Biotechnology to obtain FDA approval for compassionate use, for example, by referring the physician to the Physician Instructions, which can also be found on the AVM Biotechnology website.

The cost of this medication is provided free of charge to your physician. AVM Biotechnology will work with your doctor to properly understand the dosing, potential side effects and the potential methods to prevent and or treat potential side effects.

To help you through the process, Reagan Udall Foundation offers this Expanded Access Navigator which is a fantastic resource with very useful information.

Compassionate Use/Expanded Access Policy

AVM Biotechnology is committed to making investigational products available to seriously ill patients who have exhausted other treatment options. Development resources are focused on conducting clinical studies required by regulatory authorities to fully answer important scientific questions about the potential risks and benefits of investigational products, and to obtain regulatory approval.

Compassionate Use/Expanded Access offers a pathway to treatment for patients outside of a clinical study who meet the requirements as described in this policy, through AVM Biotechnology investigational products. A treating physician who can comply with these requirements, may request information about how to apply for access.

Scope of Policy

This policy applies to the provision of access to an AVM Biotechnology investigational product, which is not approved for any purpose within a country from which the request is intended to be used. This also governs the duration of time following regulatory approval of an investigational product and before its commercial availability.

Policy & Requirements

A. Patient Eligibility Criteria

To be eligible for access to an investigational product, patients must meet the following criteria:

• Suffer from a serious or immediately life-threatening disease or condition.
• Have undergone appropriate standard treatments without success and no comparable or satisfactory alternative treatment is available or exists to treat the disease or condition.
• Are ineligible for participating in any ongoing clinical study of the investigational product, which includes lack of access due to geographic limitations.
• The patient has a disease for which there is sufficient evidence of a projected benefit from the use of the investigational product and the benefit outweighs the known or anticipated risks.
• There is adequate information to support appropriate dosing for a special population of patients such as pediatric, elderly, renal or hepatic disease, etc.
• Any other pertinent medical criteria for access to the investigational product, as established by the AVM Biotechnology clinically or medically responsible individual.

B. Treating Physician Criteria and Responsibilities
The physician(s) attending to the patient(s) who is/are receiving an investigational product through compassionate use access is (are) properly licensed and fully qualified to administer the product. The physician must agree in writing to comply with:

• Any applicable country-specific legal and regulatory requirements related to providing an investigational product under Compassionate Use/Expanded Access.
• Any AVM Biotechnology requirements in terms of medical criteria, reporting of patient outcomes, safety reporting, drug supply/use and protection of intellectual property.

A treating physician may submit questions or requests regarding the proigram to AVM Biotechnology directly, by phone (+1-206-906-9922), or e-mail (compassionateuse@avmbiotech.com).

For more information, you can also visit the FDA’s Expanded Access webpage.