NEOCART® REGENERATIVE MEDICINE ADVANCED THERAPY (RMAT)
The sponsor of an IDP can request several special designations from the FDA which places the therapy in a special category. One such designation is Regenerative Medicine Advanced Therapy (RMAT). A drug is eligible for RMAT designation if (1) the drug is a regenerative medicine therapy; (2) the drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and (3) preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.¹ As further described herein, Ocugen’s NeoCart® therapy is a therapeutic tissue engineering product, which is considered a regenerative medicine therapy as defined in Section 506(g)(8) of the Federal Food, Drug, and Cosmetic Act (FDCA).² It is intended to treat, modify, reverse, or cure an articular cartilage lesion of the knee, which meets the definition of a serious condition in accordance with 21 Code of Federal Regulations (CFR) 312.300(b).³ Further, preliminary clinical evidence for NeoCart® indicates that it may address an unmet medical need for patients with articular cartilage lesions of the knee. Ocugen was granted the RMAT designation for NeoCart® on May 19, 2022.
Specifically, NeoCart® is a three-dimensional (3D) tissue-engineered disc of autologous chondrocyte-derived neocartilage. The drug product is derived from human chondrocytes sourced from the patient embedded in a collagen solution within a Type I bovine collagen support. NeoCart® is implanted in a cartilage defect via a mini-arthrotomy and secured to the defect with a collagen-based adhesive identified as CT3 bioadhesive. The amount administered is dictated by the size of the defect to be treated, with the surgeon cutting a piece of the implant to match the configuration of the prepared defect. The product is designed to perform like native articular hyaline cartilage at the time of surgical treatment and to rebuild a patient’s own knee cartilage to treat pain at the source and to restore a congruent functional joint surface, with the goal of preventing a patient’s progression to osteoarthritis, a serious medical condition. To receive Neo Cart®, an adult ≥ 18 and ≤ 65 years old, with a KOOS pain score of ≤ 65 with one or two treatable articular cartilage lesions of the distal femur with total area greater than or equal to 2 cm² and less than 6 cm².
NEOCART® EXPANDED ACCESS PROGRAM (EAP)
Ocugen’s EAP will be an open-label (information is not withheld from participants or researchers), single-arm, multicenter program providing NeoCart®, an IDP with RMAT designation, treatment access to ortho patients with symptomatic knee pain indicative of an articular cartilage defects of the knee in the US who are otherwise deemed ineligible for participation in a NeoCart® clinical trial. Ocugen will consider making NeoCart® available through the EAP only after the NeoCart® clinical trial begins and only in response to a written request from a licensed treating physician and/or surgeon specializing in articular cartilage lesions of the knee. The decision to grant or deny a written request is at the sole discretion of Ocugen. Ocugen cannot guarantee approval of any written requests for NeoCart® IDP. If a written request is approved, to the extent allowed by applicable law, regulations and, patient informed consent, Ocugen mandates the requesting physician/surgeon ensures that Ocugen receives scientific and clinical data tied to the physician’s use of the IDP. The decision to approve or deny a written request may be modified or reversed at any time by Ocugen and is subject to Ocugen’s ongoing evaluation of safety and efficacy data obtained from use of the IDP on a case-by-case basis. This decision to modify or reverse a written request may also be contingent on other factors related to chemistry, manufacturing and controls (CMC), inventory, and the NeoCart® clinical development program. Ocugen may revise or rescind its policy on the EAP at any time.
HOW TO APPLY FOR THE NEOCART® EAP⁴
Step 1: Treating physician/surgeon registers a written request with Ocugen.
- To review eligibility information, please see below.
- If you determine you meet the criteria, email: email@example.com.
- Our company representative will send you an information form and confidentiality agreement within 2 business days. This paperwork needs to be completed by the treating physician/surgeon.
- Once the information form is returned to Ocugen, Ocugen will provide a response to the treating physician/surgeon with a decision within 5 business days.
- With approval to participate, Ocugen will provide:
- A Letter of Authorization (LOA) to reference the active Investigational New Drug Application for manufacturing and nonclinical and clinical information.
- The NeoCart® expanded access clinical protocol.
- Proceed to Step 2.
Step 2: Treating physician/surgeon submits a non-emergency individual patient investigational new drug (IND) application to FDA.
- Complete FDA Form 3926 as described in the instructions.
- Submit LOA and FDA Form 3926 using the Expanded Access eRequest.
Step 3: Obtain Institutional Review Board (IRB) approval to proceed under EAP per 21 CFR Part 56.
- Prepare written informed consent form (ICF).
- Obtain informed consent from the patient or their legally authorized representative per 21 CFR Part 50 using the written ICF approved by IRB.
Step 3: Begin treatment 30 days after IND application is received by FDA (or earlier if notified by FDA).
Step 4: File follow up reports using FDA Form 3926 to update FDA on the patient’s progress.
OCUGEN DECISION CRITERIA ON EAP APPROVAL
In general, Ocugen considers whether…
- NeoCart® is part of an active clinical development program at Ocugen;
- The requesting patient has one or two treatable articular cartilage lesions of the distal femur with total area greater than or equal to 2 cm² and less than 6 cm², as represented by the treating physician/surgeon submitting the written request and otherwise confirmed through medical records;
- The patient is ineligible or otherwise unable to participate in any clinical study involving NeoCart®;
- The nature of the articular defects of the knee warrants or lends itself to intervention;
- Alternative treatment options are available and have been used;
- It is reasonable and appropriate, from a clinical and scientific perspective, to use the NeoCart® for a particular patient;
- The site at which NeoCart® will be administered has the capability, including adequate facilities, equipment, and personnel, to surgically implant NeoCart® and provide any care for the patient needed in connection with the surgical placement of NeoCart®;
- Approval of the written request would not jeopardize the supply of IDP for ongoing and planned clinical trials;
- Approval of the written request would not affect or interfere with the initiation, conduct, or completion of clinical trials, or otherwise compromise the potential development and/or commercialization of the IDP;
- Ocugen can reach agreement with the physician and/or the applicable site regarding an appropriate expanded access agreement satisfactory to Ocugen; and
- The written request, and Ocugen’s approval of the written request, would be compliant with applicable local, state/provincial, and federal/national laws and regulations, as well as industry standards.
NOTE: Ocugen may require up to 5 business days to acknowledge receipt of the written request and will provide a written response to all written requests in a timely manner. Certain factors may affect the length of the review period and may include but are not limited to obtaining permission from regulatory authorities, the need for additional information from the requestor, or other factors beyond Ocugen’s control. Ocugen recognizes that the decision to approve or deny a written request is complex and will assist where possible to make the process smooth and seamless. Ocugen commits to: (i) conduct a clinical review of all written requests by an appropriate medical officer, (ii) decide each written request in an equitable and fair manner, and (iii) use the available scientific and clinical evidence in making each decision.
¹21 USC 356(g).
²“Regenerative medicine therapy” includes “cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and 21 CFR Part 1271.” 21 USC 356(g)(8).
³FDA Guidance for Industry: Expedited Programs for Regenerative Medicine Therapies for Serious Conditions (Feb. 2019), at 3 (adopting definition in 21 CFR 312.300(b) of “serious disease or condition” for RMAT).
⁴Food and Drug Administration (FDA). Expanded Access | How to Submit a Request (Forms). Last Updated September 23, 2019. Accessed on May 31, 2022. Available at: https://www.fda.gov/news-events/expanded-access/expanded-access-how-submit-request-forms.