Genentech announced this week that positive top line results from the Roche-sponsored Phase III PEMPHIX study evaluating the efficacy and safety of Rituxan® (rituximab) compared to mycophenolate mofetil (MMF) in adults with moderate to severe pemphigus vulgaris (PV). The study met the primary endpoint, and demonstrated that Rituxan is superior to MMF in achieving sustained complete remission.
“The PEMPHIX study provides additional clinical evidence for the use of Rituxan for the treatment of pemphigus vulgaris,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “These data also demonstrated that Rituxan may provide complete remission rates and successful tapering of corticosteroid therapy that is superior to MMF in adults with pemphigus vulgaris.”
On Thursday, June 7th, the FDA approved Rituxan for the treatment of adults with moderate to severe pemphigus vulgaris (PV).
Rituxan is the first biologic therapy approved by the FDA for PV and the first major advancement in the treatment of PV in more than 60 years. The FDA previously granted Priority Review, Breakthrough Therapy Designation and Orphan Drug Designation to Rituxan for the treatment of PV. With this decision, Rituxan is now approved to treat four autoimmune diseases.
“It is our hope that this announcement will open the door to approval for other indications in our diseases and usher in a renewed focus on available treatments,” said Marc Yale, Executive Director of the International Pemphigus & Pemphigoid Foundation.
The FDA approval is based on data from the Ritux 3 trial, a Roche-supported, randomized, controlled trial conducted in France that used Roche-manufactured, European Union (EU)-approved rituximab product as the clinical trial material. The study compared the Ritux 3 regimen (EU-approved rituximab product plus short-term corticosteroids [CS]) to CS alone as a first-line treatment in patients with newly diagnosed, moderate to severe pemphigus. The primary endpoint of the study was complete remission at month 24 without the use of steroids for two or more months. (Complete remission defined as complete epithelialization and absence of new and/or established lesions.)
Results of the study showed that 90 percent of PV patients treated with the Ritux 3 regimen met the endpoint, compared to 28 percent of PV patients treated with CS alone. These results supported the efficacy of Rituxan in treating patients with moderate to severe PV, while tapering off of CS therapy. These results were published in The Lancet in March 2017.
An international panel of experts called the International Bullous Disease Consensus Group recently provided new recommendations on the diagnosis and management of pemphigus in the Journal of the American Academy of Dermatology. Based on existing European treatment guidelines, a Delphi survey process was used to help achieve international expert consensus. The consensus includes the recommendation to use an anti-CD20 monoclonal antibody (Rituxan) and corticosteroids as first line therapy options for moderate to severe pemphigus.
The Role of the IPPF
The IPPF aims to serve as a primary source of information for you regarding this approved treatment and is available to help answer your questions in the upcoming months. If you are considering Rituxan as a potential therapy, please consult your healthcare provider. Inform them of your medical history, and ask about the potential side effects.
The IPPF’s Peer Health Coaches (PHC) are pemphigus and pemphigoid patients who help more than 1,200 patients and caregivers each year. These specially trained PHCs reduce patient anxiety and uncertainty while providing unbiased disease and treatment knowledge. You can find our PHCs engaging the community through social media, emails, phone calls, and in-person support. The goal of our PHC program is to ensure we help every person who needs assistance in the shortest amount of time possible.
Genentech Access Solutions
Genentech is the drug company that produces Rituxan (rituximab). Genentech Access Solutions is a resource for people considering Rituxan as a treatment option. It may be worth contacting Access Solutions directly regardless of whether or not you have health insurance.
Genentech recently announced an important FDA decision that could potentially impact future treatment options for pemphigus. Here at the IPPF, it’s especially exciting when we get to share good news related to research and treatments. The full press release from Genentech can be found here. The following is an excerpt:
The U.S. Food and Drug Administration (FDA) has accepted Genentech’s Supplemental Biologics License Application (sBLA) and granted Priority Review for the use of Rituxan® (rituximab) for the treatment of pemphigus vulgaris (PV). Last year, the FDA granted Breakthrough Therapy Designation and Orphan Drug Designation to Rituxan for the treatment of PV.
“We are committed to developing medicines for rare diseases with limited treatment options, such as pemphigus vulgaris,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We look forward to continued work with the FDA to hopefully provide patients with a new treatment for this serious and potentially life-threatening disease.”
The sBLA submission is based on data from a Roche-supported randomized trial conducted in France which evaluated Rituxan plus a tapering regimen of low dose oral corticosteroid (CS) treatment compared to a standard dose of CS alone as a first-line treatment in patients with newly diagnosed moderate to severe pemphigus. Results of the study show that Rituxan provides substantial improvement in pemphigus vulgaris remission rates and successful tapering and/or cessation of CS therapy. These results were published in The Lancet in March 2017. Genentech is currently conducting another Phase III study in PV which is evaluating Rituxan plus a tapering regimen of CS compared to Cellcept (PEMPHIX, NCT02383589).
My name is Rudy Soto. I am from the great state of Texas and have lived there all of my life. I am married to a wonderful woman, Jennifer, who is my greatest supporter. We have four awesome children—two girls and two boys who range in age from 5 to 23. My motto is Can’t Grind Me Down, which I took on after I achieved remission in November of 2016. To me, it means that no matter how long my journey has been, this disease is not going to beat me. I am going to continue to live my life to the fullest and enjoy myself, my family, and my friends. This disease will not control me. I will control this disease.
My journey with pemphigus began almost eight years ago, and it has been a long one. One summer, as we were set to go on a cruise, I noticed a small lesion on my chest. I did not pay much attention to it, but I applied an antibiotic cream so as not to get infected. My wife and I went on our cruise, and I never thought twice about the lesion. After returning home, I noticed the lesion was still there and that I also was starting to get a few on my scalp. This got my attention because it was painful to get a haircut. I went to my family doctor who said it was a type of virus and prescribed a topical cream. I applied the cream daily as prescribed, but to no avail. After three weeks, I went back to my doctor. He said it was a staph infection and prescribed a steroid cream. All the while, I noticed blisters appearing on my arms and torso. I continued to apply the cream for a month or two. Still no improvement, and it was getting worse. I went back to my family doctor, and he prescribed a more potent steroid cream. After another two months, he finally said I needed to see a dermatologist. This was almost a year after I first noticed symptoms.
Can’t Grind Me Down: To me, it means that no matter how long my journey has been, this disease is not going to beat me. I am going to continue to live my life to the fullest and enjoy myself, my family, and my friends. This disease will not control me. I will control this disease.
The dermatologist ordered a biopsy and prescribed a topical steroid ointment. He said the results would take a few days to come back from the lab and that he would contact me. After four days, he said I needed to see him right away. Well, that brought fear and stress because the questions began: Is it cancer? What will I do? Is it treatable?
When we met, he said it was pemphigus vulgaris (PV). I asked him what that was and how I got it. He explained that it was not contagious, that it was an autoimmune disease, and it was treatable. He went into great detail, and we discussed the treatment options. We started with a high dose of prednisone—80mg per day—and also started methotrexate. I began using a series of different ointments, shampoos, soaps, and lotions to see what would help the healing.
The prednisone helped, but as we tapered down weekly, the lesions/blisters began to reappear. I also noticed new ones. With the new lesions came questions from family and friends because the disease activity had now appeared on my face. As I continued high doses of prednisone, I noticed that my moods changed. I became irritable, felt more stressed, even depressed at times. I began to shut myself off from everybody.
I also began to gain weight. At the beginning I weighed 165 pounds, but gained almost 40 pounds while on prednisone. My family also noticed the mood swings and the changes in my appearance. My dermatologist had warned me about the side effects of prednisone, but I didn’t believe him. I was wrong. Along with all of the side effects, I had weekly blood work to be sure my liver was functioning correctly.
Every few weeks, we would taper the prednisone. When I reached 30-40 mg, I had a flare up. We tried different types of oral medication—Imuran, dapsone, and methotrexate, to name a few. We would increase and decrease doses of prednisone to find a comfort zone, but that did not work. I stayed on this roller coaster ride for about four years. Different medications, ointments, lotions, etc. You name it, I’ve tried it.
The main concern for my dermatologist was that he wanted to beat this PV, or what he thought was PV, with oral medications. We finally began to discuss other options, including Rituxan infusion. I remember that visit clearly because we talked about the side effects. I asked him what the probability was for me to get one or multiple side effects from this treatment. He gave me a number that I do not remember, but I told him I needed to discuss it with my wife.
When I finally did find the IPPF, the amount of support, encouragement, and care I received was unbelievable.
I wasn’t the only one going through this. My family was confused, too. They asked questions, looked it up on the computer, and did their own research. My wife was a rock, telling me, “You will beat this, and you will get better.” She reassured me there was hope. We discussed the option of Rituxan, and at my next appointment, I asked questions: How would it be administered? Who would administer it? Is it chemotherapy? Would I lose my hair or get nauseous? My dermatologist answered all of my questions and more. He said he wanted me to see a specialist in Dallas who dealt more with pemphigus patients and get his opinion on treatment.
My wife and I drove three hours north to Dallas to see the specialist. We entered the exam room and answered the assistant’s questions. The assistant left the room and returned with the doctor, who looked at the lesions on my scalp, face, and torso and said, “You have pemphigus foliaceus.” I asked him what that was, and he explained to me in detail the difference between the two.
He asked if I would mind if he brought in some students. I said, “Sure, I don’t mind if it’s going to help others.” He stepped out of the room and brought back a team of at least six students! The doctor explained my symptoms and showed them the blisters and lesions. They all took notes. The doctor asked if he could take pictures, and I agreed. I was impressed—I actually had a team working on my case. We discussed Rituxan and treatment, and we made an appointment to for the infusion.
The day of my first infusion, my wife and I woke up early. I packed a bag with some reading material, snacks, and headphones. The oncologist said it would take eight hours to fully administer the treatment, and it would be done slowly to monitor for side effects. My wife stayed with me for a couple of hours and watched me sleep. I was exhausted after the treatment, but I still made the mistake of going to work the next day. I had a second treatment two weeks later, and it also lasted eight hours. This time, I did not go to work the next day.
I did not see any immediate results after my first two treatments. It took about two months after my second treatment to notice a change. My prednisone dosage was tapered again. This time, there was no flare. We tapered 5mg every two weeks until I reached 10mg per day, then we tapered 1mg every week until I reached 5mg per day. I was given a Rituxan treatment every 6 months for almost 3 years until I reached remission.
I have rambled on about my long journey through this ordeal. My experience has been been similar to many pemphigus patients, though we did not have the support many find after receiving a diagnosis. You see, my wife and I did not know about the IPPF and their support until two or three years after being diagnosed. When I finally did find the IPPF, the amount of support, encouragement, and care I received was unbelievable.
This is why I am so interested in helping others with this disease: so no one feels like they have to go through this journey alone. They are not alone. There is an entire family at the IPPF that will go through every step of this journey with them. Good, bad, ups, or downs, the IPPF staff and community is there.
When I was asked to join the team as a Peer Health Coach, I could not say no. It is an honor and a privilege to be working alongside Marc, Becky, Mei Ling, Jack, and all of the other staff members that make this foundation what it is. It means so much to me to be able to offer help to patients who may only speak Spanish. Knowing that there is someone to talk to who can relate to what their experiences is always a spirit-booster.
My name is Marlis Lippow, and I reside in Northern California. I participated in a randomized, double-blind, double dummy study evaluating rituximab infusions vs. 2,000 mg of mycophenolate mofetil (Cellcept®). I had previously received rituximab infusions so I had a pretty good idea of what to expect if I was to again receive it. I had three previous rounds and my doctor said the effects should last about six months, after which I would probably need another round. I was lesion-free for about seven months before the lesions started to return. I also was on CellCept and prednisone, so I know how those affect me.
Learning About the Trial
My doctor mentioned a clinical trial, answered my many questions, and asked me to think about it. I returned a month later for a followup appointment and there was another doctor present. She was talking about the trial and it seemed she expected me to be a part of it. I was still unsure and had more questions. She did explain that before I could be accepted, I’d undergo a screening (ECG, chest x-ray, and blood work). That was great, I would find out how I am doing. If I passed the tests, I could decide if I wanted to participate. The trial included a stipend, $50 for each session for gas and parking. That sounded good since I live about 45 miles away.
Making the Decision
My doctor and I discussed the pros and cons of the assorted medications and what I’d need to take if I did not participate in the trial but still needed rituximab. Either way, the side effects are not pleasant. Basically, we talked about the lesser of the two evils.
I learned my doctor is referred to as the Principal Investigator (PI) and the other doctor is the Sub-Investigator (SI). The SI would be seeing me every month. Since the SI is not my primary doctor, it is very important she have a complete grasp of my medical history. During my visits I would have blood work and urinalysis done. The PI would get the test results and be aware of my progress and any possible problems. If he felt there was a concern, he would end my participation in the study.
I also learned I could opt out of the study at any time if I became uncomfortable.
In the end, I chose to be in the trial.
My Trial Experience
Throughout the study, I felt my doctor was most concerned about my well-being, as he should be. He even called me in between visits and that gave me a good, positive feeling.
I received two initial infusions two weeks apart. After about five months, I received two more, also two weeks apart. By the third round I no longer had any sores. I was told that I was “controlled” and after the last infusion, I’d be in remission! My doctor told me this remission should last anywhere from six months to three years. I am hoping it will be longer!
Don’t be worried about the infusions. The infusion nurses are angels and take wonderful care of you! They are kind, let you know what to expect, and give you an idea of how you will feel. If you have any questions, you will have the phone numbers for the PI and SI and are encouraged to use them.
Clinical trials are not for everyone. In fact, there are many qualifying and disqualifying criteria set by the drug manufacturer. I encourage everyone to consider participating in a trial to help advance research on new and emerging pemphigus and pemphigoid treatments. While the short-term benefits help us now, the long-term benefits may change the lives of patients for years to come.
Momentum for the Orphan Product Extensions Now, Accelerating Cures and Treatments Act (OPEN ACT) has stalled in the Senate.
In November 2014, I used the chemotherapy drug Rituxan off-label for my rare disease, Immune Thrombocytopenia (ITP). The decision was made after careful consideration of all the possible outcomes. I was desperate for relief since ITP causes internal bleeding that can be fatal. This thought stayed in the back of my mind as I watched my platelets drop and my bleeding episodes increase in severity.
Ultimately, I decided it was worth a shot to see if Rituxan could put my rare disease in remission. When it was successful, I was thrilled and shared my success with the rest of the ITP community. To my surprise, many ITP patients told me they did not have access to Rituxan because of the off-label status. When I first heard about the Orphan Product Extensions Now, Accelerating Cures and Treatments Act (OPEN ACT), I was thrilled! Finally, legislation was presented that would allow rare disease patients to have access to FDA approved drugs that are deemed safe and effective for other conditions.
During Rare Disease Week last year, I discussed my story with Congressman Gus Bilirakis of Florida, who introduced the OPEN ACT to the Energy and Commerce Committee. Congressman Bilirakis — a huge champion for patients — and his staff worked hard to have the OPEN ACT included in the 21st Century Cures Act. The bill passed the House in July 2015 by an overwhelming vote of 344-77. The momentum has stalled in the Senate though, so now patients must act. Recently, the Senate Health, Education, Labor and Pensions Committee (HELP), listed bills that were a priority for their version of 21st Century Cures, and for some reason omitted the OPEN ACT. I will be on the Hill for Rare Disease Week this year to push for the inclusion of the OPEN ACT on the HELP Committee’s priority agenda.
For the rare disease community and patients as a whole, the OPEN ACT will provide critically needed treatment options for underserved populations. It will help fill in the gaps between diseases with limited or no treatment options and new drugs under development. I encourage all patients, regardless of their illness to reach out to their Senators and express support for the bill. Repurposing FDA approved drugs will create new data that provides the foundation for further research. Ultimately, the OPEN ACT can unlock new treatments and potential cures for rare diseases. I am living proof that repurposing drugs can save lives. Looking back, the decision to use Rituxan paid off more than I could ever imagine.
I encourage everyone to join the conversation on social media using the hashtag #CuresNow on Twitter, Facebook and Instagram. Many of our representatives are participating with us. This is our time to show lawmakers that we may be rare when identified by specific disease or diagnosis, but together we are a movement!