FDA Approval Gives New Hope to Patients With Rare Genetic Disease

By Pat Anson, PNN Editor

Lisa Kehrberg was once frightened about her future. For years the retired family practice doctor and mother of two would suffer severe bouts of unexplained abdominal pain, headaches and nausea that would leave her hospitalized for weeks at a time.

“I was doubled over, rocking, vomiting and crying with the worst pain of my life. Worse than labor, appendicitis, or anything else I'd experienced. It was a hot, burning pressure that was like lava and hot razor blades filling up my abdomen,” Lisa recalled.

She was eventually diagnosed with a rare genetic disease called acute intermittent porphyria, which causes toxic molecules to build up in the body. The same disease killed Lisa’s brother in 2011. And she thought the same fate awaited her.

“One of the most common causes of death from porphyria is suicide. This isn't surprising. I always wonder how people who are sick like me keep surviving. To live in continuous excruciating pain every minute of every day with no end in sight is quite the challenge,” Lisa wrote in a 2016 column for PNN.

It was about that time that Lisa entered a clinical trial program. Every four weeks she’d travel to Houston from her home near Chicago for injections of an experimental drug. Over time, her symptoms began to improve and the porphyria attacks that used to occur monthly became less frequent.

LISA KEHRBERG, MD

Like other participants in clinical studies, Lisa wasn’t allowed to talk publicly about the drug she was getting – until now.  

The Food and Drug Administration has just approved the use of Givlaari (givosiran) for the treatment of adult patients with acute hepatic porphyria (AHP). Approval was granted based on results from placebo controlled trials involving 94 porphyria patients. Those who received Givlaari experienced 70% fewer porphyria attacks compared to patients receiving a placebo.  

“Prior to getting givosiran I was bed-bound for close to 6 months straight from severe muscle weakness and paralysis issues. I no longer have paralysis and most of the muscle weakness has resolved,” Lisa said in an email. “The rate of new attacks has decreased greatly, finally giving my nerves a chance to heal after 22 years of attacks and 6 years of back-to-back attacks.”

“These attacks occur suddenly and can produce permanent neurological damage and death,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in a statement Wednesday. “Prior to today’s approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks. The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients.”

The FDA approved Givlaari under its breakthrough therapy, priority review and orphan drug designations, which provide incentives to companies in the development of drugs for rare diseases. Approval was granted to Alnylam Pharmaceuticals, which expects Givlaari to be available to healthcare providers by the end of the year.

There are about 3,000 people diagnosed with active porphyria in the U.S. and Europe. Due the wide array of symptoms the disease has, it can take years before an accurate diagnosis is made.

“The FDA approval of Givlaari is an important milestone for our community, as we now have a new treatment option for adults living with acute hepatic porphyria,” said Kristen Wheeden, Executive Director of the American Porphyria Foundation.

Image courtesy of Alnylam Pharmaceuticals

“AHP can have a profound impact on the lives of patients and their families. Porphyria attacks are associated with severe, incapacitating pain, often requiring hospitalization for management. In addition, many patients struggle on a daily basis with chronic symptoms related to their disease. The approval of Givlaari is exciting for our community.”

Lisa Kehrberg isn’t out of the woods just yet. She has permanent nerve damage from years of porphyria attacks. But her future is a lot brighter than it was.  

“For newly diagnosed patients, I strongly believe this treatment has the ability to stop the progression of the disease and will allow patients to lead a normal, functional life,” she says. 

Opioid Hysteria Has Gone Too Far

By Lisa Kehrberg, MD, Guest Columnist

I’m a 43-year-old physician who retired due to illness at the age of 39. I have a rare genetic disease called acute intermittent porphyria (AIP), an extremely painful and disabling condition.

Due to an enzyme deficiency, AIP causes toxins to buildup in the liver. The symptoms of porphyria are primarily neurological with the most notable being abdominal pain -- a burning sensation that is almost unbearable. The pain is similar to what I’d imagine it would feel like to have a blowtorch placed against my stomach and back.

Acute porphyria also causes peripheral neuropathy in the hands and feet. Along with the pain comes severe nausea, vomiting, headaches, fatigue, muscle weakness, motor neuropathy, and fluctuations in blood pressure and pulse. About 10 percent of AIP patients have a severe form of the disease referred to as “high excreter, recurrent attacks.”

Unfortunately, I am in that 10 percent.

Initially, I only had monthly attacks lasting 3-5 days, starting in my teenage years. Somehow, I managed to complete my education and training and became a physician despite that.

I was not finally diagnosed with AIP until the age of 39, when I suffered a life-threatening porphyria attack. It was almost too late for me at that point, as the attack was so severe that I was no longer able to work or do much at all. There is a one percent mortality rate during each AIP attack and I’ve had hundreds of them, so I’ve been lucky.

My older brother died unexpectedly at the age of 39. Genetic testing of autopsy samples later determined he had the same AIP gene mutation as I have. He died prior to my diagnosis and his gene mutation was discovered as I lay in a hospital bed being told my diagnosis.

LISA KEHRBERG, MD

At first, I felt such strong relief that my life was saved and sadness for my brother. But as the months passed, and I became sicker and more in pain, I started feeling a bit jealous of my brother. He was able to at least die with some dignity and is no longer suffering.

The pain that I experience is severe and the only thing effective enough to bring it down to tolerable levels is opioid medication. I’ve tried everything possible. Pain is a subjective experience and only the person experiencing it can know the severity and what helps to improve it.

I have difficulty understanding the response from some in the medical community, government, media and general public, who are so focused on “opioid addiction” that they are unable to see patients like me and empathize with us.

The media’s response has been extremely damaging. It seems people do not understand that addiction is a separate issue from pain management. Why is it that every time prescription pain medication is discussed, it's only in reference to addiction and the opioid epidemic? What about people like me who live with a life-threatening and severely painful disease? Not many reporters seem interested in that side of the story.

I have watched now as countless pain patients have taken their own lives due to discontinuation of their pain medication, often without any warning or consent. Physicians are not the problem in this. Physicians want to help patients. Physicians are being misled, brainwashed and even punished into thinking that prescription opioids usually lead to addiction.

Fortunately for patients like me, palliative care is a growing field and I’m so appreciative of my palliative care physician. I’m frightened for the future, not only for myself, but really for everyone. Pain affects everybody at some point in their lives. Whether it’s you, a family member or a friend -- pain will be there.

Everybody should be afraid of the direction where things are going. Even cancer patients at end of life are being denied appropriate pain treatments. Insurance companies are denying coverage for pain medications and getting away with it. I encourage everyone to please use common sense in this climate where the pendulum has swung too far in the wrong direction.

Lisa Kehrberg, MD, is a retired family practice physician who specialized in pain management. You can read more about Lisa at the American Porphyria Foundation’s website.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

My Journey From Doctor to Chronic Pain Patient

By Lisa Kehrberg, MD, Guest Columnist

I'm a 41-year old family practice physician living in the Chicago area. I worked in private practice directly after residency and then worked for the Veterans Administration in an outpatient clinic the remainder of my short career.

Much of my work involved treating patients with chronic, non-cancer pain. Little did I know at the time, this was more of a training course for me to become the very patient I was treating. 

In 2011, my 39-year old big brother died suddenly and unexpectedly at home. He was a criminal defense attorney living in our home state of Oklahoma at the time. His death was shocking since I was unaware he had any serious medical conditions. Getting his medical records was even more shocking. His physical symptoms were attributed to psychological causes. 

His death was the worst life situation I had experienced. I'd never felt such emotional pain. I also began to have physical symptoms. I had bouts of severe abdominal pain, headaches, vomiting, dark urine, numbness in my hands, and fatigue. 

In 2013, when I was the same age my brother died, I had very severe abdominal pain with vomiting and foot drop. This time the pain was too intense to tolerate and I went to an emergency room. I was admitted and had a CT scan, endoscopy, and a colonoscopy. All of these tests were unremarkable, yet I was getting sicker each day.

Initially, when speaking to the hospital doctors involved with my care, I assumed the diagnosis would be found and I'd receive appropriate care. The first surprise was, after admission, they refused to treat my excruciating pain. I was doubled over, rocking, vomiting, and crying with the worst pain of my life. Worse than labor, appendicitis, or anything else I'd experienced. It was a hot, burning pressure that was like lava and hot razor blades filling up my abdomen. My stomach distended to appear 9 months pregnant.

LISA KEHRBERG, MD

Doctor after doctor walked in and witnessed this and continued to refuse ordering opioids. After all the tests were complete and normal, the doctors were very rude to me and implied this was all a psychological problem.

I was shocked and in disbelief. How could my colleagues not believe me? Did they think I was lying? And why would I lie? I had a busy life with two young children, a husband and worked full time as a physician. I had rarely gone to doctors in my life and only taken opioids after the few surgeries I had.

Clearly the doctors didn't listen or believe me, because on day 3 of the first hospital stay, I was discharged home, doubled over in the most excruciating pain ever. I was unable to tolerate even liquids and vomited continuously. At home I never even made it upstairs. I lay on my couch getting sicker and sicker. I was getting short of breath and having palpitations. My pulse was very rapid and blood pressure high.

I went to a different hospital emergency room within 24 hours of discharge from the first hospital. After about a week of tests, the doctors were able to diagnose me with a rare genetic metabolic disease called acute intermittent porphyria.

Before figuring out the cause of my pain, doctors at this second hospital not only listened to me, but believed me. My pain was very aggressively treated the entire time I was there. I was believed, as all patients should be. Time wasn't wasted on judging and all energy went towards helping me.

Eventually I received hemin, which is an infusion used to treat porphyria. I was diagnosed and received treatment just in time and fortunately I survived, unlike my brother. 

Learning to Live with Porphyria

Because the disease had became so severe before being diagnosed and treated, I have permanent nerve damage. I have severe abdominal pain from visceral neuropathy every day. I have also had back-to-back porphyria attacks since 2013. Porphyria attacks are known to be excruciating and a patient experiencing one will normally be hospitalized and get IV morphine.

What happens to patients like me who have back-to-back attacks without a break ever? Do I live in a hospital? I spent the first 3 months of this ordeal hospitalized the majority of the time. I began to wonder if I would spend the rest of my life as an inpatient. But I wanted to live and go back to my life somehow.

The only way to stay out of the hospital is palliative care; treating the symptoms at home. I've been unable to work and spend most of my time too sick to leave my house or do much. The disease is very unpredictable, so it's impossible to plan much. At least I can see my children every day. I survive by putting my energy into loving my children and taking things hour by hour. Just making it through one day is a challenge. 

One of the most common causes of death from porphyria is suicide. This isn't surprising. I always wonder how people who are sick like me keep surviving. To live in continuous excruciating pain every minute of every day with no end in sight is quite the challenge. Now imagine living this way with no pain medication. I will tell you that it's not possible. The pain from this disease if left untreated is not compatible with life.

At that first hospital, I tried to find a window I could open and jump from. I felt like I was on fire. I wasn't depressed. I was in pain. How would someone like me exist in life without pain medication? I couldn't. Impossible. It would be like performing abdominal surgeries on patients without anesthesia. It's so beyond my comprehension how the medical community can have such little empathy for those who are sick, in pain, and disabled. 

My palliative care doctor is wonderful. He has compassion and listens to me. He believes me and doesn't judge. He has saved my life and the reason I'm able to attempt living life and not continuously be readmitted to the hospital.  

Last summer I went to a new doctor who specializes in pain and is a physiatrist. I was hoping he may have some ideas. He listened to my story, then said he couldn't help me since I took opioids. He told me my pain must be "emotional.” He said patients without cancer should not be taking opioids chronically.

I asked him what someone like me can do. I explained it’s like having a blow torch in your colon all of the time and how do you exist that way? He shook his head and rolled his eyes. I left crying.

I still cry when I think of that interaction. How could a physician, a person supposedly trained to offer healing and compassion, treat any human being this way? If I was healthy and was working in the same hospital as this doctor, he would be inviting me to lunch. But because I met him while sick and disabled, I'm judged. No compassion, much less treatment. 

Now that I've entered the world of chronic pain, I've had the opportunity to talk to hundreds of patients suffering like me. The majority have uncontrolled pain. They are forced to jump through many hoops each month just to get the medication needed to offer a little relief. I've talked to many who plan suicide someday, because they are unable to get appropriate pain management. This isn't depression. It's pure physical torture. I can't imagine people needlessly dying because they are unable to get medication to ease their suffering. Medication that's available. These people have children, are someone's child, have siblings, friends, etc. 

Physicians see a patient for 10-15 minute appointments and don't understand that the person’s pain continues after that office visit. Physicians who think opioids shouldn't be prescribed for chronic non-cancer pain are wrong. Ask these same doctors how they plan to treat the pain and you learn there is no plan.

I suspect these doctors don't understand the concept of continuous pain. If a doctor refuses to treat a patient’s chronic pain and that patient commits suicide from pain, then somebody should be held accountable. This is criminal and completely preventable. 

I'm saddened to see what's happening with the CDC's opioid prescribing guidelines. I would really like the CDC to suggest how to treat my severe back-to-back porphyria attacks. Too many doctors are being investigated for opioid prescribing. This is meant to scare doctors not to prescribe. Doctors should be receiving training on how to prescribe opioids and treat chronic pain patients. Doctors who treat chronic pain patients are saving lives everyday. They should receive only praise.

Lisa Kehrberg, MD, is a family practice physician who specialized in pain management. You can read more about Lisa at the American Porphyria Foundation’s website.

Lisa is also featured in this report on Acute Intermittent Porphyria:

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.