Expanded Access? Previously enrolled / completed Terms study

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Help! Anyone else out there with similar experience with Tovaxin? This is a long post but worth considering a new possibility on the road to full recovery.

I do not have MS, but my immediate family member was in Tovaxin study completed by Opexa Therapeutics. I cannot begin to describe how positive the results were for her. Unfortunately, as many of you might already know, once you have completed one of the trials you are disqualified from any future clinical trials (now Tcelna) and simultaneously unable to receive any of this miracle medication until the FDA approvals are provided in some far, far, possible light years away future. She experienced no relapse at any point while taking the medication and returned to a routine 9-5 work schedule, life, weight, etc. etc. One year after the final dose of the medication was administered, she fell into a downward spiral. True to form, MS has painfully regained its footing in her body leaving her worse than she was before. We received confirmation that she was given the medication and not the placebo--so I believe that the temporary complete reversal of the symptoms caused by MS were solely a result of receiving Tovaxin. She was placed on the list for open label extension and that was later terminated after her final injection. Budget / re-branding reasons which was so infuriating. Like they gave a person the miracle drug, took her positive results, and used those to later fund a different project that technically restarted from square 1.

For those not familiar:
Opexa: http://www.opexatherapeutics.com/Home/default.aspx
Study Info: I don't know why the results are no longer available on the clinical trial .gov website but there is a summary here: http://www.opexatherapeutics.com/tcelna ... -overview/
Open Label: was terminated (insert very angry emoji here) : https://clinicaltrials.gov/ct2/show/NCT ... exa&rank=4

Anyway....

More unfortunately in her case, she has not been able to safely use any of the other treatments on the market since this trial ended and has not been on any MS medication for many years. Pain relieving medication has been prescribed over and over again and it's been so ridiculously frustrating because you can only imagine what a person with MS and no MS medication goes through everyday.

I've spoken with the clinical manager at Opexa (M. Murry) several times and she has not been able to provide a lot of new information aside from the reasons for re-branding (to T-celna target SP MS from Tovaxin RR MS) and other hopes that the medication would receive the approvals after what seems like years of paperwork are filled out and final trials are completed. Tovaxin and Tcelna are basically the same biological measuring different stages of MS.

I want to reach out to the community and see if there are others in the same situation. If there are, I might have come across a solution and so I also want to see if any one else has read through the requirements of Expanded Access (info here: http://www.fda.gov/ForPatients/Other/Ex ... 041768.htm) I have outlined the requirements for both patient and physician and listed the seemingly easy 14 steps in the process to applying for the Expanded access. I've also called the number listed on the information website and believe it or not, you actually get a real live person working for the FDA who very patiently and more surprisingly, willingly provides any information and answers as many questions as they are able.

What are your thoughts? anyone else out there previously on tovaxin / tcelna with positive results? What are you taking now?

We know that this Tovaxin/T-Celna did not help everyone in the trials, just as Copaxone, Tecfidera, Gilenya, Aubagio, Tysabri, and Lemtrada did not help everyone once FDA approved. Due to the fundamental inconsistencies of Multiple Sclerosis and the unpredictable symptoms each person experiences, we must be willing to accept that treatment plans are going to be very different for each individual. Similarly, we should consider that those with MS cannot be treated with the same set of standards as those with other diseases—and exploring other routes is vital in some cases such as ours. We are positive that this medication allowed her to regain muscle function and avoid flare ups for the longest stretch since being diagnosed. The FDA and Opexa both could reject our application and we are willing to accept that possibility, but if they did I do not want it to be for lack of trying. This possible approval would be a life changing step forward for our family.

all responses with advise / input welcome.

- Ziggy



Reference Link: http://www.fda.gov/NewsEvents/PublicHea ... onal_Drugs

There are three categories of expanded access:

(1) Expanded access for individual patients, including for emergency use

(2) Expanded access for intermediate-size patient populations

(3)Expanded access for widespread use.



The requirements for the application are as follows:

(4) The patient and his or her licensed physician must both be willing to participate.

The patient must:

(5) Have a serious† or immediately life-threatening disease or condition;

(6) Have no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; and

(7) Be unable to obtain the investigational drug under another IND† or to participate in a clinical trial.



†Serious: A disease or condition associated with morbidity that has substantial impact on day-to-day functioning. Short-lived and self-limiting morbidity will usually not be sufficient, but the morbidity need not be irreversible, provided it is persistent or recurrent. Whether a disease or condition is serious is a matter of clinical judgment, based on its impact on such factors as survival, day-to-day functioning, or the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one. (21 CFR 312.300)



†Individual patient INDs Non-emergency (this is the IND that we would be applying for)

Under this type of expanded access, FDA may permit an investigational drug to be used for the treatment of an individual patient by a licensed physician. The physician must determine that the probable risk does not exceed that of the disease for the individual patient. The FDA must also determine that the patient cannot obtain the drug under another IND or protocol. Under this type of expanded access, the regulations require that a) treatment is generally limited to a single course of therapy for a specified duration; and b) at the conclusion of treatment, the licensed physician or sponsor must provide FDA with a written summary of the results of the expanded access use, including adverse effects





The process is as follows:

1. The Expanded access must fall into one of the three categories listed above In this case I believe her request should fall into category (1) - Expanded access for individual patients, including for emergency use.

2. The Physician must be willing to participate along with the patient. The physician should review the requirements for expanded access with the patient and obtain informed consent.

3. Patient must meet all requirements for the application (listed above) In this case she has a serious disease or condition in which there is not currently a satisfactory alternative treatment that she is able to take. She is also not able to obtain the investigational drug and Opexa has confirmed that she is not eligible to participate in any upcoming clinical trial. Their requirements currently state that they are not accepting patients that participated in past clinical studies. (confirmed with M. Murray – Opexa Therapeutics – Clinical Development Manager)

4. Individual patient expanded access submissions made by individual physicians are submitted as new INDs. If a licensed physician is making the individual patient expanded access submission, he or she also must be willing to manage the use of the investigational drug and the patient’s medical care.

5. Physician must complete the FDA 1571 Form

6. Provide a statement that this is a request for an individual patient IND for treatment use. The physician will need to specify whether it is an emergency IND or individual patient IND. This statement should be at the top of the correspondence and on the mailing cover.

7. Provide a brief clinical history of the patient including:
the diagnosis
the disease status
prior therapy
response to prior therapy
the rationale for requesting the proposed treatment, including a list of available therapeutic options that would ordinarily be tried before the investigational drug or an explanation of why use of the investigational drug is preferable to use of available therapeutic options

8. Indicate the proposed treatment plan including:
the dose
route
planned duration
monitoring procedures
modifications (e.g. dose reduction or treatment delay) for toxicity.

(Reference a published protocol or journal article if appropriate) (this seems applicable: Fox E, Wynn D, Cohan S, Rill D, McGuire D, Markowitz C. A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design. Mult Scler. 2012 Jun;18(6):843-52. doi: 10.1177/1352458511428462. Epub 2011 Nov 6.

9. Include the chemistry, manufacturing and controls information and pharmacology and toxicology information The requirement for this information may be met by providing a Letter of Authorization (LOA) to refer to this information if it has been previously submitted to FDA (for example, to an existing IND or NDA). This should be the same LOA or information the physician received for performing the prior clinical trial during the TERMS study. The letter of authorization should include relevant identifying information, such as the sponsor’s relevant application (e.g., IND) number.

10. Provide a copy of the informed consent from patient and approval of use by an appropriate Institutional Review Board (IRB) **(Will be obtained prior to initiating treatment if approved by IRB)

11. You will need to provide the FDA with the a statement that specifies the training, experience, and licensure of the treating physician. This can usually be found on the the first two pages of a Curriculum Vitae typically contain this information and are usually sufficient.


After Submitting the Application:

12. 1. Treatment may begin 30 days after FDA receives the IND, or earlier if FDA notifies the treating physician that the expanded access use may begin. The treating physician must ensure that IRB review is obtained in accordance with FDA’s regulations.

13. 2. The treating physician may need to provide the IND application number to the medical product company prior to the company shipping the investigational drug.