Compassionate Use of Investigational Drugs

Compassionate Use of Investigational Drugs
Elena is Programs Director at Kids v Cancer, a nonprofit pediatric cancer advocacy organization. Elena directs the Compassionate Use Navigator program, providing guidance and personal assistance to physicians and families in applying for experimental drugs. Previously Elena worked as a science and business journalist, and as a program manager. Elena holds a Master of Public Health degree in maternal and child health and an M.A. degree in journalism.

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Kids v Cancer Resources

Christina Ip-Toma: Welcome to OsteoBites. My name is Christina Ip-Toma, and I mom to osteo-angel Dylan, and the Director of Scientific Programs for MIB Agents.

Today on OsteoBites, we are talking with Elena Gerasimov of Kids v Cancer. Elena will be discussing compassionate use of investigational drugs, and she'll give us an overview of the compassionate use program, explain how to apply for experimental drugs, and discuss the resources available to both patients and doctors throughout the application process. And today we have Junior Advisory Board members, Mia Sandino, and Camille Wahl as our panelist.

So, I am very excited to have Elena with us today on OsteoBites. Elena is Program Director at Kids v Cancer, a nonprofit pediatric cancer advocacy organization. She directs the Compassionate Use Navigator program, providing guidance and personal assistance to physicians and families, and applying for experimental drugs. Previously Elena worked as a science and business journalist, and as a program manager. She holds a Master of Public Health degree in Maternal and Child Health, and an MA degree in Journalism.

I know from personal experience, accessing investigational drugs can be really confusing and it can be really daunting process, and Elena and Kids v Cancer have so much expertise in this area, and they offer tremendous resources for both patients and physicians trying to navigate this process. So we are very excited to have her here today to explain how this all works, especially for a rare disease like osteosarcoma, where there are very few approved drug options.

Before we get started, I have a few events that I wanted to share with you all. For those of you in the Boston area, we have a Boston Mingle coming up next Friday, March 31st. We promise it's going to be fun, and there's going to be free drinks and appetizers, and everyone in the  Osteosarcoma Community is invited. We'll put the invitation and registration link in the chat, and please share with everyone you know in the Boston area. And while we're there we're also hosting a Healing Hearts Retreat for bereaved osteosarcoma patients on April 1st. Please email Casey, we'll put her email in the chat too, and she will reach out to you with more information.

And we'd like to thank the sponsor of this episode: BTG Specialty Pharmaceuticals. BTG provides rescue medicines typically used in emergency rooms and intensive care units to treat patients, for whom there are limited treatment options. They're dedicated to delivering quality medicines that make a real difference to patients and their families through the development, manufacture, and commercialization of pharmaceutical products. Their current portfolio, the antidotes counteract certain snake venoms, and the toxicity associated with some heart and cancer medications. The drug peroxides is for high-dose methotrexate toxicity. All right. Mia, would you start the introductions please?

Mia Sandino: I would love to. Hi my name is Mia Sandino. I am an OsteoWarrior. I'm also the vice president of the Junior Advisory Board for MIB. I'm very honored to be here, and welcome everybody. I'm excited for this great presentation.

Camille Wahl: Hi everyone! My name is Camille Wahl, I'm 19 years old. I'm currently living in Boston, Massachusetts, and I'm a freshman at Boston University, studying Education and Human Development. I am a seven-time OsteoWarrior, and a member of MIB's Junior Advisory Board. Happy to be here, and I'll turn it over to Elena.

Elena Gerasimov: Hello, I'm Elena Gerasimov. I'm very glad to meet you all, and I think that it will be an interesting topic for both audiences, for the patients, for their families, and for healthcare providers that are joining us as well. The topic of my presentation today is compassionate use of investigational drugs for kids with cancer.

So, the Kids v Cancer is a non-profit pediatric cancer advocacy organization. It was founded in 2009 by Nancy Goodman after her son, Jacob, passed away from brain cancer. Jacob was 10 years old. Since then Kids v Cancer has championed 2 federal laws—the Creating Hope Act, and the RACE for Children Act. And we are currently advocating for passage of a third bill, the Give Kids a CHANCE Act. This new bill will give FDA authority to request studies of combination of drugs for children with cancer.

When Jacob was sick, Nancy applied to 8 companies seeking compassionate use for him. None got back to her. So, in 2016, we created the Compassionate Use Navigator to help physicians and families understand the process, and apply for drugs. We have a, today's audience, both patients' families, and healthcare providers. So, I'd like to state that while only healthcare providers can submit applications, it is very important for patients' families to understand the process so that they can initiate conversation about compassionate use to their doctors.

The Compassionate Use Navigator was inspired by the story of Josh Hardy. I would like to offer you to read it. It's available on our website, and I'll provide a link for that. So, when we created the Compassionate Use Navigator, we were aiming at overcoming informational barriers. We found that some patients do not know about this option, that there are misconceptions about FDA not allowing the request to proceed, and that there was an inequality and ability to access of drugs—meaning that only people with connections, or those who are computer-savvy be able to research the drug programs, and to apply for them.

So, I list here a few barriers and a few quotes for you about the goals, which we have set to overcome. So, I think I'll start with the definition with compassionate use. Compassionate use refers to treatment with unapproved therapies. Meaning drugs not approved by the FDA for a patient who is refractory or elapsed and not responding to standard therapy.

FDA has established several criteria to define and grant access to experimental drugs. According to this criteria, compassionate use is intended for a patient who has an immediately life-threatening condition, or serious disease, and cannot wait for a therapist approval. There should be no comparable or satisfactory alternative therapy available. And if a therapy exists, it must be no longer effective.

The primary goal of compassionate use is treatment, not research—unlike it could be in a clinical trial. So, the best way to access experimental drugs, those which are not on the market yet, is through enrollment in a clinical trial. But patients are often ineligible or cannot relocate in order to participate in a trial, and sometimes trial is not recruiting, or has ended, or eligibility criteria make school children and adolescents due to their age. In this situations, a patient may consider applying for compassionate use.

Compassionate use can also be sought for pediatric cancer patients, when off-label use of an FDA-approved drugs is not covered by insurance. We're seeing more and more situations like that now. Here on the slide, you can see a few examples that we've worked with, based on an insurance denial to covers those drugs.

An important consideration is that regulatory requirements—that the benefit of an experimental drug must outweigh the risks. And the assessment of that is done by treating physician, and will be reviewed by FDA later.

So, I'm going to say a few words to set the correct terminology. Patient advocates, physicians, academics, and journalists usually use the word 'experimental' or 'investigative drugs' or, obviously, 'compassionate use.' FDA and many pharma companies refer to compassionate use as 'expanded access.' Another widely used term, 'pre-approval access,' precisely describes that the drug has not been approved yet.

In Europe, following terms can include, Named Patient Program and Early Access. If you read literature, you might run into those terms. And the Single-Patient IND or investigational new drug, is applications that the company files to FDA for compassionate use for a single patient. And this term is also used to describe compassionate use. Something like, to open Single-Patient IND.

Separately, there are also expanded access programs for multiple patients offered by drug makers. Also, the term has the word 'expanded access,' just like FDA when it refers to compassionate use. These programs are different from compassionate use because they're intended for multiple patients—usually have specific eligibility criteria, and are often listed on These programs can be offered as a transition for patients, after trial has ended, and before a drug is approved.

In all of the [inaudible] program, might not be possible for a child, whose medical history does not meet the eligibility criteria, or due to the patients age. So, somewhat like a clinical trial. It is expanded access, but it can have its own criteria in order to join that program, which basically, brings the patient who doesn't qualify for it back to square one. So, in those cases, physician will still seek single-patient compassionate use. Even in situations when the drug company has an open expanded access program.

How do patients find compassionate use drugs? Before an application for a compassionate use drug can be submitted to FDA or to a drug manufacturer, a physician needs to identify the drug that has a potential to help patient. I call it "Step Zero." Here there are several ways how patients and doctors can learn about experimental drugs. For patients, it's very often through the word of mouth, through patient organizations, through research on the internet, or they would hear from their physician who would initiate conversation about compassionate use. For healthcare providers to find compassionate use drugs, they need to be familiar with the ongoing clinical trials. They can hear from colleagues, they can see what's in that drugs company's pipelines, on the manufacturer's website, or they can use other websites such as PubMed.

After they have identified the potential compassionate use drug, there are 3 steps in the process to apply for access to that drug. The first one is to apply to drug manufacturer. The application will need to be submitted to the Food and Drug Administration. And the physician will need to receive approval from its IRB.

So, to apply to a drug manufacturer, you will need to find contact information for the company, first of all. You can try locating the expanded access link on the company's website, if you don't have the company's contact. Most larger companies have posted information, with an email address and a phone number; or they might have a online form that you will need to fill out if you want to apply for the drug.

If you are contacting the company by email, you should include in your correspondence an indication and a brief clinical history of the patient. The history should include data such as the patient age, gender, weight, allergies, diagnosis, prior therapy, response to the prior therapy, and the reason for your request, including an explanation of why the patient lacks other therapeutic options. There might be several back-and-forth communications, or a company might want to speak with you on the phone.

If the company agrees to provides a drug, it will issue you a letter of authorization. You will need to submit the ID number given on that authorization, together with the letter of authorization to the FDA. I will explain in a little more detail later in the presentation. There is the link here to the sample letter of authorization. Yes?

Christina: Sorry, Elena. Is this step the applying to the drug manufacturers? Is that something that the physician has to do, or that the patient can do?

Elena: The whole process of applying to compassionate use can be done only by a physician.

Christina: Okay.

Elena: So, the patient's, of course, are welcome to write to that drug manufacturer; and sometimes those letters are helpful as a support, especially for companies whose in denial. But the official request for access to a drug must be submitted by a physician. It's a free format—in the physician's own word. "I have such and such patients. The patient relapsed. Here is the [inaudible]. This is why I believe that the drug you have would be helpful." You know, so just a letter. And sometimes there are specific questions, especially if it's an email form of the drug manufacturers website, they will ask for what they want. If there is nothing but just the email address for instance, then it's basically a letter.

Christina: Okay, and I think on your website, you have some examples, right? Some templates?

Elena: We do. We did provide sample letters. Yes.

Christina: Great.

Elena: So the initial time commitment for a physician, would be about 1 hour, it's my estimate, to find the contact information and to write an email with a brief clinical history. The companies' also usually post the response time—the anticipated response times, that they'll get back to a physician within five days or a week, usually something like that. But that's just to get back on initial request. And the issuance of a letter of authorization may take longer.

So here I have a drug manufacturers examples of policies slide. Since the passage of the 21st Century Cures Act, the drug manufacturers are required by law to have a policy on compassionate use publicly accessible. So the most difficult step in the whole process is obtaining agreement from a drug company to provide the drug. Companies are under no obligation to provide drugs for compassionate use, and FDA cannot compel a company to do it.

So the information a company would post would include the: how long it will take them to respond to request, contacts, and also criteria for providing the drugs. But not all companies have complied with this requirement, so, you know, the larger companies might be expected to have this information, some small companies still don't have it, and some have simply posted statements indicating that they do not provide compassionate use access.

I have 2 examples here. One company's post states that due to supply constraints, it cannot grant access. And another company says that the drug will not be available for compassionate use until a phase 2 study is complete. But as a patient advocate, I believe that even that such policies are posted on the website. It is worth contacting the company with a request. You don't know when the phase is completed, you know, I think we should always give it a try.

Step 2 is to apply to FDA. It is a good idea to notify the FDA of your request. Is it before you submit the request? Or right after? I mean submit a request to drug manufacturer, because FDA, at this point, won't know yet that you're seeking compassionate use. Applying to the Food and Drug Administration involves filling out Form 3926, which is only 3 pages and takes about 5 minutes to complete if you have clinical history in front of you. There are instructions on how to fill out the form on FDA's website.

In addition to clinical history, you will need to provide a treatment plan. This will include the planned dose, route and schedule of administration, planned duration of treatment, monitoring procedures and planned modification to the treatment plan in the event of toxicity. So, the whole process needs to be sought through.

It is often useful to reference published studies, if there are any, that have used the drug in a similar manner. Reaching out to peers who have requested compassionate use for a specific drug is also helpful. And you will need to include the letter of authorization, which grants FDA the right to reference the drugs companies' IND, so it can review the description of the manufacturing facility, drug regulatory data.

The response time of FDA [inaudible] is about, it could be immediate, for oncology patients, it's about 2 to 3 days for non-emergency requests. I would like to stress, that FDA has a totally fantastic resource called, "Project Facilitate." This is a pilot program, I believe it was created couple of years ago by the Oncology Center of Excellence, and it provides comprehensive support to oncology healthcare professionals in completing expanded access requests. It is essentially called center which connects you to an FDA officer.

If they will consider scientific likelihood of drug's benefit in each case, and can provide companies contact information, it will answer your questions, and help visit paperwork. And even if you have no questions, it is a good idea to notify Project Facilitate of your upcoming or submitted request.

FDA also has an email and a phone number for patients to call and talk about compassionate use. And I encourage families to do that. It's absolutely great resource, you know. I really hope that this facilitation from FDA, the likelihood of obtaining the compassionate use drugs, or following the process in an efficient manner really increases. It's a great resource for us.

Christina: I'm just going to insert some props for the FDA here because, just from personal experience, they are amazing to work with. You think it's going to be this large government, bureaucratic entity and it's not at all. Like, you talk to actual people and they know your name, and they will look for your application, "We're going to keep an eye out for it," and they're super responsive. So I just want to give some, you know, feedback that just from my personal experience. They've been amazing to work with.

Elena: Absolutely, I agree. I think they're very responsive and they want to make it happen. And actually I had cases when FDA officer would review the application and say, "You know what, we can suggest a different drug," which might be also in a compassionate use basis, but they have a wealth of information on their position. They know what's going on. What drugs are in development? And It's a great resource.

This slide I have a FDA mailing addresses, where the documents need to be sent, and I try to make a screenshot of the Form 3926 here in the bottom. There are different addresses for biologics and for the drugs. All of that information can be found in FDA website, but I just wanted to call attention to it.

So the last step, the third step, is the IRB review and informed consent. After the drug manufacturer agrees to provide for drug, the application to FDA, and IRB approval, they can be initiated simultaneously. In non-emergency cases, the FDA will need to see the IRB approval before the start of the treatment. You will first need to obtain informed consent from the patient, and the a sign from the IRB Chair, or as a member of an IRB. A link to sample informed consent is provided here.

And I also want to say that the full IRB committee meeting is no longer necessary. It's not necessary to wait, you know, a month for the whole committee to meet. You will just need to contact the IRB Chair, or another member if the Chair is not available, and request sign off on your request. And please ask for help from your clinical research staff in arranging the sign off.

After all of this steps are completed, the investigational drug will be shipped directly to the physician who is responsible for overseeing the investigational treatment, and reporting the outcomes to the sponsor, IRB, and the FDA. In the rare instance, since most children are being treated in academic centers—which obviously have IRBs—in the rare instance of the request comes from a practice where there is no IRB, we provide some resources how to find an independent IRB. And we estimate the time frame for about an hour to obtain informed consent, and about an hour to locate the Chair of an IRB and get a signature.

You notice that I mentioned several times 'emergency' and 'non-emergency' situations. So, 'emergency' is defined by FDA, when it's urgent need for treatment, and there is no time to waste. The original case of Josh Hardy, is that I referenced earlier, was an emergency case. Josh was a cancer patient. He had kidney cancer since he was very little, and he beat that 3 times, and then he needed to have a bone marrow transplant, and after the bone marrow, he got an infection with adenovirus. And his compassionate use request was actually for mitigation to beat the adenovirus—he was dying from that. So that was an emergency case, literally.

In emergency, you need to call FDA. FDA usually grants emergency user requests the same day, over the phone. There's no paper works. The certain paperwork can be submitted later, you can proceed quickly. So, you will send the paperwork, which is required after the treatment has started—within 15 days of treatment initiation. And the same applies when there is not sufficient time to secure IRB review prior to treatment, you may proceed just after obtaining informed consent that is required. And then the IRB must be notified within 5 working days of emergency use. There is a separate phone line to contact FDA when you're requesting emergency use, and they also work after hours, so that's a good resource to know about.

Family expectations for compassionate use. So patients cannot submit compassionate use request themselves. This leads to expectations—the expectations that the physician will be on board and will pursue the request. One study of pediatric oncologist found that in 73% of cases, conversations about compassionate use, they're initiated by a healthcare provider. So that the doctor alluded the family that there is such an option. But many families are very knowledgeable about drug development, and about what's on the market, and most are willing to do everything in their power to obtain a therapy they believe might save or prolong a child's life.

Unfortunately, often companies deny compassionate use requests. There have been numerous cases, instances of families fighting the denial of a compassionate use drug. That was the case of Josh Hardy. When social media, and television, and journalists, and Congress people were involved and trying to get a drug for Josh. I believe that Josh's case was the start of the Compassionate Use Movement and the Patient Advocacy Community.

Families now sent pleas to drug companies. They create energetic social media campaigns. They seek help from politicians, from celebrities. They offered to pay for an investigational drug. That was often offers that a company received when the drug for Josh was requested. The advocate said, like, "Well is at all about the cost? You know, we will cover the costs." Or I know about the cases when the families tried to buy a drug from an overseas pharmacy, if it's available there. This is why, you know, because families are willing to fight like that, this is why it is encouraging for the family when the provider the becomes a family's advocate.

As an example, I'd like to read you an excerpt from an actual email exchange—a letter an oncologist sent in response to a drug company denying his request. So, hear this: "I know the reality. The family most definitely knows the reality of this disease, and I know that this may not work or do anything for the patient. But all we ask is for a chance. In conclusion, I hope you all can understand where the family's coming from. I will continue to support them. Especially the patient during this process and will advise them the best I know how. But I cannot and will not tell them to stop continuing to fight."

Physician considerations for compassionate use. Families look to their pediatric oncologist for direction, and emotional, and medical support. At the same time, physicians must balance uncertainty about the potential benefits and toxicities of a drug against risks of the disease itself. Some physicians may be reluctant to engage in discussions about compassionate use. The reasons for this may be: inability to identify promising investigational drug, concerns about unproven effectiveness or potential toxicities of the drug, lack of clinical evidence to justify investigational treatment for a specific indication, or safety concerns related to the condition of a patient.

Because the compassionate use application requires knowledge of the regulations and administrative process, there have been instances when an oncologist, who has never submitted the request, is intimidated by their unfamiliar process and the presumed time commitment. So we encourage doctors to educate themselves, or seek assistance from organizations that provided from the FDA, and research the investigational drugs, and advocate for their patients.

For the assistance for physicians and families, this slide is about our Compassionate Use Navigator. It can navigate the program before Project Facilitate was initiated by FDA. We work directly with families and have experience with denials. We can explain the process like a drug manufacturers contact information, provide templates, and helped draft initial request to drug manufacturers. They can help us in Form 3926, although we obviously do not have access to clinical information of the patient, and they can answer questions. My contact information is on this slide.

Another resource is another organization that provides assistance, is Reagan-Udall Foundation for the FDA. They provide guidance and expanded access to physicians and patients. On their website, there is an explanation of the application process, including a link to clinical trials that would include those expanded access programs for multiple patients, that I mentioned in the beginning when I explained terminology.

The companies included in the directories of Reagan-Udall provide, they submit information themselves, so the directory may not be comprehensive, but that's a very good resource to start. And there is also a link to an electronic submission for non-emergency request to FDA. But that company, as well, will send just by email to the FDA. And I provide the contact information for Reagan-Udall here.

My last slide is about other [inaudible] to try. So I want to say a few words about this, it's a federal law. So for decades, the mechanism of expanded access to investigational therapies, has been criticized for blocking access to investigational therapies because it was very difficult to get compassionate use. A lot of advocates were not satisfied with how it was working. So, the result of this criticism, Right to Try Laws were passed in many states. And in 2013, a Federal Right to Try Law was enacted.

Similar to compassionate use, Right to Try is intended to provide patients with terminal illnesses access to unapproved drugs. So what are the differences? Unlike under the single-patient IND, under the compassionate use program through FDA, under the Right to Try, eligible drugs must have completed phase 1 trial process and phase 2. So it's earlier in the clinical studies process. Right to Try also cutout FDA's oversight from the whole process.

FDA does not review approve requests for Right to Try Act Use, because a lot of criticisms was coming, mistakenly blaming FDA for not granting the request. That was not the case, because the first step to receive authorization to use compassionate use drug was always drug manufacturer. Also individual Right to Try Act request do not require IRB review approval. So both of those steps are cut out, and patients can submit the request themselves rather than going through a physician.

So why not consider this strategy? Because it sounds genuinely quite good, right? So, first of all Right to Try, 'cause no [inaudible] comes the major obstacle to obtaining access, which is the Drugs Board denials of compassionate use request. You still have to ask the manufacturer to provide the drug. Because it does not require drug sponsor to provide an investigational product, some people say that the Right to Try actually provides only the right to ask. In this regard, it's not different from the existing compassionate use pathway.

Some pharmaceutical companies oppose Right to Try, even though it shields them from liability because companies prefer to proceed with the expanded access mechanism that provides FDA safeguards. They want to know that the FDA has revealed required, that they have the agreed and authorized.

There is no reliable data, but year after Right to Try was enacted, [inaudible] I believe in 2019 only handful of patients reportedly received drugs for Right to Try, they can submit the request. But in my experience, it's highly likely that the company will tell them to go through the compassionate use mechanism. So, this is the [inaudible] mentioned that is an option, but I personally have no knowledge of successful request, or of patients using this pathway. So this was my brief overview about compassionate use. And I'd like to thank you, and I will be glad to answer your questions.

Mia: Yeah, thank you so much. That was great. I've got a question coming up. So, this happened to me as well because I had to, you know, use some investigational drugs, but I did not go through the compassionate use program. Often drug manufacturers offer financial assistance program for drugs, which is what I did, that aren't covered by insurance, how was applying for compassionate use different from applying for a discounted price or no-cost drugs from the Drug Manufacturers Foundation, or financial assistance program? So, how would it be compared of the two?

Elena: It's a very good question. There are several differences. First of all, compassionate use drugs are free, and they would most likely be issued for the condition of single course of therapy. It won't be an ongoing, it won't be for something chronic. And that would be for the patient who cannot access it some other way. So their financial assistance program for patients, usually come because the patient's go to those programs, because their insurance doesn't cover. That make me think that most likely the drug has been approved, because if the insurance has a right to consider coverage and, you know, support or deny the coverage, that would be for the approved drug. Compassionate use is for the unapproved drugs, those that have not come to the market yet—those which are in the clinical trial. But in the clinical trials, issue of insurance is not rising.

So this is, I guess, for the different stages of the product development that [inaudible] approved versus unapproved drug. And then for the length of the therapy, to some extent not necessarily. Usually the compassionate use drugs will not be even considered by the insurance, because insurances exclude all experimental drugs. The drug needs to be approved. Going through the assistance program at the company is a very good pathway for those who are fighting the insurance company. And in my experience companies are quite generous and really trying to provide help to patients who cannot afford their drugs otherwise.

Christina: Elena, can I just clarify? So when you say an approved a drug, because there's just over all FDA approved, but especially for a disease like Osteo, a lot of, especially when you're looking at, you know, targeted therapies, a lot of those drugs may be FDA approved but not for Osteo, so they're considered off-label drugs. So does the compassionate use off-label drugs, so it may be an FDA-approved drug, but not approved for use in Osteo. Or?

Elena: Right. So it's approved for a different indication, and therefore insurance would decline coverage, correct? Yes, that happens. Unfortunately. When the FDA set up compassionate use program, it was not for this purpose. It was not for those circumstances. It was exclusively for people who cannot get through clinical trial. That's why, you know, some of the terminology for it, it's still called pre-approval, access.

Christina: Okay.

Elena: We're talking about before the drug was approved. But I hear about more and more cases when people go through the compassionate use pathway to get the drug because insurance is not covering, and the companies are questioning and always by themselves they say like, "Well, they don't know what to do. The drug is approved, the drug is on the market, the doctor can prescribe it. You know, why are you applying to compassionate use?" That's a loophole in the whole sedation. It hasn't been resolved yet, and I think this is something we, as a patient advocates, need to work on. You know, about coverage of cancer drugs, because waiting for the peer review studies be to be published, to prove that this indication, so the drug box, you know, for some expanded indications, you know, takes time.

And we need to create a mechanism. And now it's actually happened to be compassionate use to come and apply for the approved drug, just because it's for a different indication. Yes, patients, do that.

Christina: So people do that, but was it kind of the primary and...

Elena: It was not the primary goal. I think it was not even anticipated that that's what's going to be happening. You know, my guess only could be that we are learning this such a speed, you know, the discovering, you know special it is a targeted therapy, precision medicine, rediscovering different genes and mutations, and enrich, "Oh the drug could be actually effective against this, and this one." You know? And I think it's a result of the recent scientific progress. But yes, they are basically seeing patients asking for compassionate use for approved drugs now as well.

Christina: Thank you.

Mia: All right. I have the next question based off personal experience that I had. So I was treated with Mepact, also known as MTP-PE or mifamurtide in 2017. My family and my physician went through about an 8-month process to obtain it, and I ultimately did receive the treatment. Mifamurtide is widely used in other places outside of the US, but for some reason it's not FDA-approved here. So, I'm wondering is the process any different or easier if there are a lot of established precedence of patients with a specific disease applying for a drug?

Elena: If there are a lot of patients with specific disease applying for a drug which is not approved in the United States or for approved drug, that would be, I think, the first distinction. You know, there is a provision, which I'm not very familiar with, since it's outside of compassionate use about personal drug importation from another countries for personal use, this is something that FDA handles. And, I guess, if the drug is approved in another country and it's needed for a patient here and for some reason it's not approved here yet, I believe there is a pathway to import the drug.

For the multiple-patients here applying for that unapproved drug, you know, FDA actually likes to collect this information, because it would allow FDA to consider suggesting to a company opening of a new clinical trial. For instance, if you take an example with another indication, you know that there is a drug which is being studied for one indication, but then, you know, we seeing more and more patients applying for it to compassionate use because they have a different indication, but they have reasons to believe that the drug is working.

That might lead FDA to join to the company and say, "Look, you know, I've been seeing so many of them, why don't you open a trial?" And the trial can be very small, it could be 5 patients, 10 patients, to start with. And, as far as I know, that has happened. Sometimes it's even happened within the same hospital, you know, I would talk to an oncologist because there's, "You know I have such and such patient who is looking for this drug." And while they're working on getting such drug, I get a message saying, "Oh, now I have two patients looking for this drug." So I would hope that that encourages companies to open more trials and to look into studying the drugs in different indications.

Mia: I have another question come in. You had mentioned that the biggest hurdle is getting drug manufacturer approval, based on your experience and working with patients and their families, what are the best strategies to secure compassionate use approval from the drug manufacturer?

Elena: That's an excellent question. It's actually [inaudible] I like to talk about that, you know, and I wish I knew the best strategy, but I can tell you what works if that's possible. The best one is a proof that this drug is going to help the patient. So if there are previous instances of this company providing drug to somebody needed compassionate use, and seeing good results, basically saving patient life or prolonging patient life, they're more likely to provide it again. You know, so good justification.

You know, I had a case once, when the company said, "No." They declined to provide the drug for a patient for whom they were advocating, and what helped us, we found a doctor in a different institution across the country who said, "You know what, you know, I actually use this drug for my patient." And then we asked him to get on board with the treating physician of our patient, and talk to the company together. And when they did that, the company change their course and provided the drug.

I mean, it wasn't like that. It wasn't until one conversation. It wasn't very easy. We didn't locate the physician right away. It all took time. But you know, I saw that it worked, you know, if we would have stopped at the first denial, the patient probably wouldn't get the drug.  But we kept looking, you know, and they found somebody who's done it. So that's very helpful. It has to be some kind of clinical justification that the drug you're asking for has a potential to help, and the company will look at that.

And in my experience, companies developing the drugs for patients because they want to save lives. So they are not just declining to provide the drug for no reason. There is usually some justification, unless, you know, as it was in the Josh's case, it was supply issues. It's much harder for smaller companies, because they don't have enough drug manufacturer.  But, you know, that I believe the former had speaker of the biotechnology industry organization a while ago, you know, several years ago when I was at a conference. told drug companies that if you are developing a cancer drug, you have to prepare yourself for the fact that you will be asked to provide compassionate use. So you just start thinking, how you're going to do it, you know, at the same time, when you starting to develop the drug.

And I think that most of them do and create those expanded access programs when they can. So, I think we're seeing positive dynamics, at least, you know, from a time when Josh needed the drug, which was in 2014.

Mia: All right. I have the next question from the audience. The care teams are so busy and the application process seems like a lot of work and extra administrative work, how can patients and caregivers help their oncologist/care team during the application process? And what types of resources does Kids v Cancer offer oncologists to ease the burden and help them through the process?

Elena: It's also very good question, we hear it a lot. I tried to stress. that the time commitment is not so huge, but, you know, I don't want to minimize it—from looking for the company's contact, and sending some email, and summarizing clinical history. Yes, it takes some time. Absolutely. If there is staff, who are able to help with that, that's excellent. You know, most large academic medical centers do have the staff and they do have experience. But certainly, there are doctors who have never submitted that request, who don't have, you know, administrative resources to do that.

And as I said, FDA can guide, they can help with filling out of the form. We have templates. FDA has templates, how to write a letter to the drug manufacturer, You know, this is just like really an email, you can send it on very short email, if you don't have time right away. "I wanted to apply such and such drug, you know, I will provide you the clinical information later," you know, just like to initiate the process, and I'm more than happy to do that. That's what I've been brought on board to Kids v Cancer to do in 2016, that's when I joined the organization. I can help fill out the form, but not fully. But I will guide, I will explain.

And when you actually, you know, I guess when you're listening to presentation, it seems like, "Yes, look at that, the drug manufacturers, the FDA, IRB, and researching the drug, it all takes time." After you've done it and you know what drug you want, it's not that time consuming. The difficulty will come if you are denied the drug, because you would need to go back and forth. You know, I would encourage every physician to go back and forth with the company, not just take no for an answer on the first try. It doesn't mean that the drug will be provided, that depends on every single case. But yes, it makes advocacy on the part of the physician, and I tried to say that they believe this is what families now expect, that the doctor would be an advocate for a patient. And in my experience, most oncologists are advocates to their patients.

Christina: And Elena, to that point, you had given us a nice anecdote about that instance, where you were able to pair up the 2 doctors—one that had experienced a good outcome with one of the drugs with the other to help them get approval, which was a very encouraging, but I was just curious, do you have a sense of, kind of, what the success rate is after getting the first denial? Like is there a pretty encouraging rate once you have that back-and-forth conversation?

Elena: I could not put a number on all that. But here is what I would say, I believe that situation improved dramatically in the past 7 years. We used to be seeing denials all the time. And as I said, when Nancy first asked for the drug for Jacob, no company got back to her because they were not obliged to respond to emails they get. And now they will [inaudible]. You know, especially those who posts those policies, they have people, they will get back to you. That's already was the first big step. And after that, you know, we start about why it's this drug or why not this drug, and will it help the patient or not? You know, and I believe if there is a medical justification for that there is a chance that the drug is going to help, most likely the patient will be provided the drug.

That the social media campaigns that we had to do for Josh, you know, going in CNN, FOX, and France. That's how it actually ended up. Or, you know, in enlisting a Washington football team player, you know to treat all of his supporters of over a million people, you know, saying that they need help for Josh. I think this is no longer needed. So I would say that the success rate is increasing. That's what I would say. You know, I'm much more optimistic now, if you would get a compassionate use requests than it was in the beginning when I just started working on that.

Christina: All right, that's encouraging. Thank you. Mia do you want to

have one more question before we wrap up?

Mia: Sure. What is the typical turnaround time once you contact the drug company for compassionate use to when the patient has the drug in hand or I guess in, you know, the nurses' or oncologist's hand to start treatment? Is it easy to get an emergency use exception for the 30-day waiting period?

Elena: Yes, absolutely. Emergency use does not have a 30-day period. As I said, FDA would approve it over the phone. You know, you call them at 9:00 at night, you know, and you know, if you have a agreement.

What is the time frame? Okay. So for non-emergencies, the company will get back to you, within 5 to 7 days. Sometimes it's 2 to 3, depends on the company. After that, depends on whether they agreed right away to provide the drug, let's say it will take them another week, you know, going back and forth, you know, if they'll agree. So that would be 2 weeks.

After you submit the paperwork for oncology patients, 2 to 3 days in non-emergency cases. They say that. So 3 days approval. IRB, depending on how soon you could locate the Chair of IRB, you know, I would say, you know, it could be next day if you prepare the paperwork. Again, if you have a clinical staff sack who can help fill it out, that just one person doesn't have to do all that. So we can look at that very optimistic scenario, 2 weeks in non-emergency. I would say more likely it would be a month to 2 months probably. So because all of the steps would require that, you know, all this paperwork that needs to be done.

In an emergency, it could be as soon as next day, you know. Plus, you know, we need some time for shipment of the drug; because the company ships the drug. It would be next day probably. It's also very optimistic, the day after. You know, for emergency request, Josh got his drug in a week, but that was through all the [inaudible] TV interviews, and everything. And that was for emergency. In a week. So in that case, it was actually, you know, very long because Josh was dying from the virus. So, you know, I would say it's realistically to think a month to 2 months to get the drug depending on also the condition of the patient.

If it's obvious that the patient can continue on the current therapy, but we want to explore that, you know, based on the results of the current therapies, and you know, there isn't such a hurry. But you know, let's say 2 months is a good estimate.

Christina: Okay, great. That's also not super long. So I'm sure we could sit here and ask you questions all day, because it's really good information and super helpful. And we just want to thank you Elena for joining us today and for your commitment to pediatric oncology patients everywhere. There's a wealth of information on the Kids v Cancer website, so we'll make sure to send out that link so everyone has that. Elena, can we share some of the information on your slides as well because there was a lot of great...

Elena: Absolutely. I put all this mailing addresses and everything with this idea that slides could be perused afterwards, you know, as a reference.

Christina: Great. So we'll share those with everyone who registered today. More information on this and all OsteoBites can be found on YouTube, our website:, or your favorite podcast place. And next week we are talking to Dr. Amanda Marinoff from UCSF about Myc amplification as a prognostic biomarker in osteosarcoma. So thank you again Elena for being here today. And to Mia and Camille, as always you guys are awesome, thank you. And thanks to our sponsor, BTG Specialty Pharmaceuticals, and thank all of you for joining us today. We hope to see you next week. Thank you.


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