Getting the treatments we need to market

-Written by Tiffany Westrich Robertson

In August 2017, IFAA attended a meeting at the Food and Drug Administration (FDA) so that we could speak on behalf of those patients who are running out of treatment options and who may benefit from new therapies that target a different mechanism of action.  This article is based on that visit.  Note: Each country has its’ own regulatory process to evaluate the safety and efficacy of drugs, which includes a similar format to what is described below.  

 

The need for new treatments

Patients living with autoimmune & autoinflammatory types of arthritis are often treated with biological products that are designed to target specific molecules that block the actions of cells, which in turn, helps control the inflammation associated with these diseases [1]. The first biologics were TNF- inhibitors (Tumor Necrosis Factor) but since they came to market other products have been developed that target different molecules, or have “different mechanisms of action”.  Examples include B-cell inhibitors, T-cell inhibitors, Interleukin-6 (IL-6) inhibitors, Interleukin-1 (IL-1) inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase 4 (PDE4) inhibitors – and more are currently being tested in clinical trials.  But why so many and why are the different targets important to patients?

Disease Individuality. While there are several autoimmune and autoinflammatory diseases where arthritis is a component (“autoimmune arthritis”/”autoinflammatory arthritis”), in a handful of these diseases the arthritis is a major clinical feature – and therefore, these diseases are often treated with the same types of treatments.  But even within the same disease class, there is no one-size-fits-all solution, because no two patients have the same percentage of genetic predisposition combined with the same environmental triggers.  Therefore, patients with the same diagnosis may respond very differently to treatments.  Having different mechanisms of action opens up options to patients, particularly to those who are not responding well to one or more commonly prescribed therapies.

Duration of Efficacy.  Biologic treatments typically have a lifespan of 2-3 years before efficacy diminishes (in most patients, not all).  But this is one reason why more treatments are needed, as some patients who have been using biologics for some time will eventually run out of options.  Additionally, between 30 – 40% of patients fail to respond or become intolerant to anti-TNF therapy.  When this happens, the strategy is usually to try another TNF inhibitor or switch to a medication with a different mechanism of action [2, 3].

Disease Progression.  In these diseases, structural damage is permanent and irreversible. Therefore, finding the right treatment, and mechanism of action, is necessary to avoid additional disease progression and disability.

 

The regulatory process (U.S. Food and Drug Administration – FDA)

20525289_10155561037289556_6714436075980852470_nIt takes an average of 8-10 years for a biologic to get to market once the drug is developed and tested in the lab.  After initial studies are done in animals, a plan is designed to test the product in humans (via clinical trials) and then submitted to a regulatory agency for review and approval to proceed (See Figure 1).  In the United States, this is done at the Food and Drug Administration (FDA). At the end of the second phase clinical trials, the FDA and the pharmaceutical company meet to review findings and to determine how the larger “phase three” trial will be done. After some additional written communications between both parties, and if the trials are approved to move forward, the final phase of testing the product on humans will begin.  This last phase of trials will help the pharmaceutical company create product safety and efficacy treatment profiles and determine recommended dosage.

 

pre market FDA after phase 3
Click on image to view on FDA website

 

When the clinical trials are completed, the pharmaceutical company applies to present their data to the FDA – in what is called an Investigational New Drug (IND) Review (Figure 1 – red circle). In the United States,  the information is first presented to an Arthritis Advisory Committee (AAC) [4], who convenes to review all submitted data and offer their professional opinions regarding safety and efficacy of the proposed drug prior to the final FDA ruling. In August of 2017, IFAA attended one of these Investigational New Drug (IND) Reviews, both to better understand the process and to speak on behalf of patients who need access to new treatments.  This following information is a summary of that experience. 

 

Investigational New Drug (IND) Review

FDA-panel
Photo:  Advisory Committee Meeting at FDA The AAC consisted of 13 voting members including the Chair, authorities knowledgeable in rheumatology, orthopedics, epidemiology or statistics, analgesics, related specialties and consumer reviewers (patients). 

IFAA was interested in attending this meeting so that we could speak on behalf of those patients who are running out of treatment options and who may benefit from new therapies that target a different mechanism of action.  To do this, we first had to find funding to get to the FDA; once secured, we registered online to reserve a ten minute time slot during the Public Comments segment of the meeting. The particular drug under review was tested to treat Rheumatoid Arthritis (RA), so we then reached out to fellow RA patients to ask why they want – or need – more therapeutic options.  Their responses were used to help formulate our presentation.

The meeting began promptly at 8am, with the AAC seated in the center of the room, the pharmaceutical company representatives to their left, and the FDA and media to their right.  As a registered speaker, I sat in the audience near the center aisle, so I could easily access the podium when it was my time to speak.  After brief introductions of the AAC members, it was time to begin.

The pharmaceutical company presented information about the product, the method of application (injection form with a syringe), and how it was different from – or similar to – other biologics currently on market.  Then they proceeded to review each individual clinical trial and the outcomes that were tested.  Outcomes included:

  • Testing efficacy based on the ACR 20/50/70 – which refers to the American College of Rheumatology rating on disease improvement. 20 = you are 20% improved, 50 = you are 50% improved, 70 = you are 70% improved. The main target in these trials was to achieve an ACR 50.
  • Testing the drug in patients “of unmet need”, particularly those who have failed more than one other biologic agent prior to the trial.
  • Quality of life measures – specifically how the drug impacted a patient’s daily experience with symptoms, such as fatigue and mental clarity.

The FDA then reviewed issues they felt were of particular importance regarding safety and efficacy.  When both parties were finished, the AAC members were invited to ask “clarifying questions”.  For each question, the correlating slide that was shown during the presentations was brought back up on the large screen.   Once all questions were answered, we broke for lunch.

 

Public Comments

When the meeting resumed, it was time for Public Comments.  At this time IFAA was called to the podium to testify on behalf of RA patients.

Excerpt from our testimony:

“While many patients do have success using existing treatments available, a significant percentage do not. This is especially important given the progressive nature of the disease and the potential for permanent and irreversible damage that can happen if the right treatment is not applied.  RA is not a one-size-fits all disease; therefore, what works for one patient may not work for another. Many patients either do not respond initially or stop responding when a treatment loses efficacy over time.

“Over the past years, IFAA has had the opportunity to speak with 100’s of patients who have tried and failed 3, 4, 5, 6 – and, in some cases, who have exhausted or are near to exhausting all treatment options.  While they all have unique stories, one similar sentiment unites them: “I’m scared. What if I fail again?  What am I going to do?”

“In a patient population where the disease is so varied per individual, access to new mechanisms of action are necessary so a greater percentage of patients can achieve clinical improvements and an acceptable quality of life. The longer patients have to wait for the right mechanism of action that will work best for them, the more irreversible damage and unnecessary disability is possible.  This will only lead to higher long term complications and a larger financial burden to our healthcare system.”

 

The AAC Discussion

Once Public Comments concluded, the AAC began deliberating about efficacy findings, safety findings, and the overall benefit-risk profile of the drug for treatment in patients with RA.  Below were specific topics for discussion:

  • Discuss the safety findings in the Phase 3 trial.
  • Discuss the dose selection for the Phase 3 trial.
  • Discuss the design of the placebo-controlled study and consider what optimal study design should be when assessing radiographic progression in rheumatoid arthritis.
  • Did the data provide substantial evidence that the drug provides a clinically meaningful benefit in the treatment of rheumatoid arthritis?
  • Is the safety profile adequate to support approval in adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs (DMARDs)?
  • Do you recommend approval at the proposed dose?

 

AAC Voting

At the end of an intense discussion, the AAC members were asked to vote first on the efficacy of the proposed drug, then on safety.  They each had a voting device with two buttons, one for yes and one for no.  Once the vote was generated electronically, the results appeared on the screen behind the panel.  Then the Moderator asked each AAC member how they voted; at this time, they had the opportunity to disclose their rationale for voting as they did.  The committee unanimously agreed that the drug was efficacious in treating RA.  However, in the vote on its’ safety profile, there were still too many unanswered questions for the committee to give their full support.

What Happens Next?

While the FDA is not bound by the committee’s recommendation, it does take its advice into consideration.  The pharmaceutical company will continue their discussions with the FDA, which will include providing any additional information necessary so a decision regarding the safety of this drug can be established.  At that time, if the FDA determines the drug can be released for market, it will become another therapeutic option for treating RA. It is also under review in other countries by their regulatory agencies.

Approving new treatments that are safe and effective for patients who rely on biologic therapies to prevent permanent, irreversible damage is necessary.  IFAA is glad to have had this opportunity to speak out on behalf of those who need it most.  We will continue following this, and all potential therapeutic options, as they find their way to market.

 

Did you know YOU can get involved in this process, too?

It’s true!  Not only can you attend FDA meetings (FOR FREE) in person, you also have opportunities to submit your comments online – which then become part of the official records used by the FDA to make their final decisions on whether or not a product goes to market.

To get started, subscribe to the ‘new’ FDA patient newsletter.  It will notify you when and how you can get more involved, in addition to alerting you about important safety warnings and product approvals.


Click here to access link to register for the newsletter.

 

Make Sure to Submit Your Comments Online When it Matters to YOU!  In just a couple of clicks you can tell the FDA why you believe a drug should – or shouldn’t – be considered for market.  All you have to do is subscribe to the newsletter and when a public meeting – like the one we told you about in this post – is happening, you have until the day prior to write your comments and submit them for the record.  You can even attach photos!

Apply to be a Patient or Caregiver Advisor.  In 2017, the FDA created the first advisory committee made up solely of patients and caregivers, who can provide advice on complex issues related to medical devices.  They also developed the Patient Representative Program. This program brings patients – and their caregivers – and the extraordinary breadth of knowledge and personal experience in more than 300 diseases and conditions they possess, directly into the regulatory medical product development and review process. They serve on 47 FDA Advisory Committees and panels to advise on drugs, devices and biologics currently being considered for approval or clearance.  Learn more.

Patient Focused Drug Development (PFDD).  Efforts to further patient engagement at the FDA have expanded, including this major initiative that started in 2012.  The PFDD heavily relies on Patient Centered Outcomes Research (PCOR) to provide information about what outcomes are most important for patients.

LUPUS PATIENTS GET INVOLVED

In September 2017, a meeting for lupus patients is convening and IFAA will be there.  If you are a lupus patient (any type) you can register to be there in person (you would have to pay your own expenses) OR PARTICIPATE ONLINE.  Patients who participate will have the opportunity to answer questions via live polls and those responses will be used to help the FDA better understand the treatment needs in patients living with lupus. Both options have limited seating, so RSVP now!  There was one for Psoriatic Disease in March 2016 (IFAA was there too!)  You can view the archives here.

 

Get Involved Outside of the US

In Europe?  Learn more about your regulatory process and how you can get involved as a Patient Advisor:  European Medicines Agency (EMA)

In Canada?  Learn more about your regulatory process.

Learn about the Common Drug Review in Canada.

Other Locations:  You can find a list of all regulatory agencies, by country, HERE. Then search their website to learn more about how you can get involved!  (Please let IFAA know if you do this and if/how you get involved!)

 


 

IFAA works hard to be patients who are “at the table” – and aim to bring those experiences to you through this blog, Systemically Connected.  Thank you for your continued support, which enables us to continue attending conference, events, & meetings that help advance care for our community and enable YOU to get more involved in your own healthcare. 

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References

[1] the next phase to our award-winning project that advances patient involvement in research

[2] Scott DL. Biologics-based therapy for the treatment of rheumatoid arthritis. Clin Pharmacol Ther 2012;91:30-43.

[3] Smolen, JS and Aletaha, D. Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheum. 2015; 11: 276–289.

[4] https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/default.htm

Happy 6th birthday IFAA!

Written by Tiffany Westrich-Robertson, CEO of IFAA, patient with Rheumatoid Arthritis, Axial Spondyloarthropathy, Sjögren’s Syndrome

6th birthday

Ahh to be six.  We see the world as hopeful, so many things to experience, so many things to try – often with little fear of being hurt or rejected.  We are open to relationships, people like the mail man or the checker at the grocery store are super cool and we get excited when we know we can see them soon.  Our knowledge of science is limited, mostly doing fun problem solving experiments, like how to make the glue in our desks into molding clay.  Oh, and people who are 40 are SOOOOOOO old.

Today, May 7th, 2017, IFAA is six years old.  While we are a nonprofit, we aren’t much different than “being six” as a human.

  • We are hopeful.  We believe strongly that if the world (public, peers, family, doctors, media, policy makers) is properly educated about DIFFERENT TYPES of arthritis that they will see that the second most “common” (word used sarcastically, as many of these are rare diseases) type of arthritis is autoimmune/autoinflammatory – or the arthritis associated with having an autoimmune or autoinflammatory disease, they will understand these diseases require a different type of research, treatment plan, and management protocol.  Doing this will result in earlier detection, referrals, diagnosis, and treatment.  It will help secure funding for treatments that are more personalized to our individual journeys.  It will help to alleviate misunderstandings among family, friends, peers, co-workers, the medical community, and policy makers.  It will make a difference. (Learn how YOU can make a difference this May 19th-21st during World Autoimmune/Autoinflammatory Arthritis Day’s virtual online race between your favorite nonprofits!)
  • We believe in relationships.  IFAA is unique in that no program or effort we take on is by ourselves.  We believe in other nonprofits, advocates, coalitions and the great work they do – and we believe that if we unite our efforts only good things can happen.   This “global network” philosophy that in ingrained in all we do has enabled us to establish solid relationships with dozens of groups all over the world – from the US, Canada, Europe, Australia, New Zealand and counting.  We think they are so cool and we look forward to working with them every chance we get.
  • We are leaders in the patient-researcher partnerships movement.  Other than awareness and education about arthritis differentiation, our other strongest initiative is involving patients ON the research team.  We get to learn about science in new ways, and be part of the solution.

Six years ago today, on my 40th birthday, I opened the mailbox to find the letter that stated IFAA was officially a nonprofit.  Today, at 46, I look back on the last few years and all that IFAA has accomplished in a very short period of time.   But one thing that is different between being a six year old human and a six year old organization is 40 is NOT old.  And 46???  I’ve only just begun.  And the same with IFAA – watch out world, here we come!

What route would you take to my party? Explaining autoimmunity

Written by Tiffany Westrich – Robertson

When I was first diagnosed with Rheumatoid Arthritis (RA), I was perplexed.  I was relatively young, athletic, ate healthy, exercised – I did not understand how this happened to me.  After some research, I learned that these diseases are partly caused by genetics, and that any family history of autoimmune disease of the 80+ possibilities constituted ‘genetic predisposition’.  There are people in my family with autoimmune issues (not RA), so that makes sense.  But autoimmune diseases are also the result of a faulty  acquired immune system, which means they are triggered by a learned, or adapted, response that is generated by something in the environment*.  Examples of some environmental triggers include smoking, infections, gut bacteria, dental decay, and even extreme emotional or physical stress.  But as of now, researchers cannot prove any one environmental trigger as the cause, and they admit some triggers are still unknown.

confusedSo how can patients understand how this happened to them, and more so, how do they explain it to others?

 

Explaining autoimmunity

Shortly after diagnosis, I heard Dr. John O’Shea, Scientific Director at the National Institute for Arthritis and Musculoskeletal and Skin diseases (NIAMS), give a presentation about autoimmunity.  Much to my surprise, it was not a speech riddled with scientific jargon, but rather an analogy that brilliantly answered the question how does autoimmunity happen.

“What if I invited every person in this room to come to a party at my house next month?” Dr. O’Shea asked.  “How would you get there?  Would you take a plane, a train, a bus, a cab?  Which route would you take?  The highway or the side streets?  Direct route or scenic?”  He gave everyone some time to ponder that answer, then continued by guessing that most of us did not live together, hence our starting points would vary and so would our paths to arrival.  “This is much the same way autoimmunity works,” he added.  The explanation that followed helped me learn an easy way to understand and describe it to others.

Here’s what I took away from the analogy:

Let’s sahouse partyy that everyone reading this post is genetically predisposed to possible autoimmune disease and you are all invited to my house for a party.  Your house is the starting point, which symbolizes your unique genetics – no one else is starting from your house except for you.  The different methods of travel and routes you take to get to the party represent the potential environmental influences – smoking, infections, gut bacteria, dental decay, and even extreme emotional or physical stress, etc.  Even though you all will leave from different places, at certain times some of you will cross paths – or in the case of the analogy, will be exposed to similar environmental triggers. Upon arrival, some of you will develop an autoimmune disease and some of you will not, even though you all were genetically predisposed and some of you, at times, even took similar “environmental routes”.   Additionally, in those who do develop disease, even if it’s the exact same diagnosis, you will still have your own individual genetic + environmental journey and, therefore, will have a slightly unique presentation and treatment response.

wow my reaction

 

 

 

 

dr oshea lab 800
 

Dr. John O’Shea giving IFAA a personal tour of his lab.  This will be the subject of a future post. 

 

 

His presentation did eventually branch into the relevancy of genetic + environmental onset in research and the challenges associated with finding pathways in populations where outcomes are somewhat individualized.  But advancements in genetic mapping, such as the work being conducted in Dr. O’Shea’s lab, are sure to keep us on the road to the treatments that narrow down solutions.

 

 

Future parties

I have a better idea now how I got to the party.  I thank Dr. O’Shea for this great explanation, and additionally for the work he and other researchers are doing to identify the paths most traveled.  Hopefully, in time, the routes to the party will be filled with known roads to avoid, and more and more people will arrive without ever developing an autoimmune disease.

 

*Note:  Those affected by autoinflammatory diseases, such as Behcet’s Disease and Still’s Disease, can still use this explanation, but with minor adjustments.  Autoinflammatory diseases are a result of a faulty innate immune system, which means that genetic mutations are the primary cause of the immune response, with little environmental influence.  Learn more about the differences between autoimmune and autoinflammatory. 

 

References
Environmental Triggers and Autoimmunity, Aristo Vojdani et al.  PMCID: PMC4290643, National Library of Medicine at National Institutes of Health.  2014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290643/
Smoking and rheumatoid arthritis: What’s the risk? Chang-Miller, Mayo Clinic. 2014 http://www.mayoclinic.org/diseases-conditions/nicotine-dependence/expert-answers/rheumatoid-arthritis-smoking/faq-20119778
Rheumatoid Arthritis and Gum Disease, Dunkan A. Arthritis Foundation, 2016 http://www.arthritis.org/living-with-arthritis/comorbidities/gum-disease/ra-and-gum-disease.php

 

 

 

 

 

Are you ready to be Systemically Connected? Take a seat!

SC at the table.png

In the last six years since IFAA has been a nonprofit, we have been “the patients at the table”.  We have been the panelists and keynote speakers, focus group participants as well the moderators, grant reviewers alongside rheumatologists and researchers, and at the offices of policy makers.  We have worked alongside over 5 dozen nonprofits, patient advocates, and advisors from all over the world, and are members of over a dozen coalitions.  We have participated, both in person and remotely, in 100’s of seminars, conferences, webinars, and meetings. 

All of these experiences have built our knowledge and expanded our resources to a level we never imagined possible.  We have continuously been told, “You all are a wealth of knowledge!” so now it’s time we pass it on to the community, so you can benefit from it! So pull up a chair – we are going to connected YOU to all of the knowledge and resources we have collected, and will continue to gather.  Let’s get Systemically Connected!

 

What makes Systemically Connected Unique?

Systemically Connected will not only turn all of our past, current, and future experiences into articles that will help you gain more information about topics that are important to you, but all discussions (including your comments) that follow each post will be collected and analyzed for research purposes and future project development.

And remember, we are patients too, so these conversations will be 100% patient led.  The patient voice really does matter at IFAA!

 

What topics are on the table?

Based on our own experiences as patients and our communications with the patient community, we will talk about topics of most interest including:

  • Autoimmunity – How can I explain it to others so they will understand?
  • New Rheumatologist – What can happen?  From new diagnosis to treatment changes and how to prepare for “the change”, it’s a real situation that many of us face.
  • Autoimmune versus Autoinflammatory Diseases – What’s the difference?  Which do I have and why does it matter?
  • Biosimilars – What should I know?
  • Misdiagnosis, Re-diagnosis, Dual Diagnosis – What’s going on?!
  • “Patient-Centered Research” – It’s great the patient is being considered, but what the heck does all of this mean for me?
  • Medical Marijuana – Let’s stir the pot
  • It’s Not Your Grandma’s Arthritis – Enough said

Also, YOU can influence what comes to the table by sending us your topic recommendations via our Contact Us page!