Acquired Hemophilia A Post-COVID-19 Vaccination: A Case Report ...
Woman Told She Won't Live Past 35 As She Lives With Six Medical Conditions
Hanna Hamm is a ticking medical time bomb — the 22-year-old will likely die before she reaches age 35.
The Claremont, California, resident suffers from six grim diagnoses, and her doctors are trying to figure out a seventh mystery illness.
At the age of eight, she was diagnosed with Ehlers Danlos Syndrome, a genetic disorder that causes joint pain, an abnormal foot structure, elbow dislocations or bluish tints to the skin, according to the National Institutes of Health.
When she was 15, she was diagnosed with Hemophilia A, a genetic disorder that causes blood clot failures. For Hamm, it was particularly dangerous, as she was going through adolescence and experiencing menstrual cycles that would last for as long as 20 days.
Haemophilia A is a rare blood disorder that usually doesn't affect women (Image:
mediadrumimages/Hanna Hamm)The diagnosis for postural tachycardia syndrome came at 20 — POTS, as it is commonly referred to, causes drastic increases in patients' heart rates when they sit or stand up. The condition causes Hamm to faint as many as 10 times per day.
At 21, lupus and Raynaud's phenomenon were added to her list of ailments.
The symptoms of lupus are many and can include muscle and joint pain, rashes, fevers, hair loss, chest pain, sun sensitivity, eye disease, anemia, fatigue or memory loss, according to the Centers for Disease Prevention and Control. It's often associated with Raynaud's phenomenon, which causes numbness in the fingers or toes, the Lupus Foundation of America says.
She also possibly has an aortic aneurism.
On top of all that, she started experiencing intense, long seizures this year at age 22, and the condition has baffled her doctors, who are scrambling to diagnose the issue.
Hamm's first diagnoses occurred when she was a young child (Image:
mediadrumimages/Hanna Hamm)For up to 20 minutes at a time, she'll lay prone on the floor, unable to move or communicate, staring blankly at the ceiling. Her husband, 28-year-old firefighter Zachary, will shake her and yell her name, but she won't wake up.
When she finally does, she's often left confused and asks her husband the same questions repeatedly.
Because of her many conditions, she said she spends the majority of her time at home with Zachary or her parents looking after her.
Her mother suffered from many of the same conditions as well, which is how Hamm might have come to be diagnosed with them.
She said she's often in immense pain and struggles to perform regular daily tasks like walking or driving.
She feels isolated, too — people have gawked at her, screamed at her and treated her poorly in public, she said, in nasty displays of ableism.
Hamm's mystery seizure condition is baffling doctors (Image:
mediadrumimages/Hanna Hamm)"You would be insanely surprised how different people treat you when you're disabled," she said. "I've had people yell at my husband calling me drunk during my fainting spells. I've had someone step on me when I've fainted before. I have had people move my wheelchair out of the way so much more."
The bullying and her inability to perform simple tasks has paved the way toward severe anxiety, depression and bipolar disorder. She said she often feels worthless.
"There are a lot of days I feel like giving up, that I'm a waste of space and someone as sick as me isn't worth being around," she said. "I feel guilty staying at home sick while my husband is out saving lives."
Hamm used to be an EMT but lost her job when the fainting spells began — it was too dangerous, both for her and her patients, for her to be out trying to help people with her condition.
She had dreams of becoming a firefighter like her dad and husband.
People have bullied Hamm for her conditions (Image:
mediadrumimages/Hanna Hamm)"I miss being able to drive and work and have a normal life and I miss being able to walk around without pain or collapsing in a syncope," she said. "I feel like I don't have a 'normal' life for someone my age, that I don't get to do a lot of things people my age are doing."
Her average day now consists of her waking up every morning, taking loads of medications and drinking water. Then, she calls her parents, who pick her up and take her to their home.
She stays with her parents until the evening, and they take care of her during her episodes.
Back at home, she showers in her chair, then settles back in bed and takes more medication.
Oftentimes, she has to crawl the bathroom because her pain or episodes are so bad.
Hanna's Raynaud's Syndrome causes her problems mostly in the colder months (Image:
mediadrumimages/Hanna Hamm)To manage her conditions, Hamm eats lots of salt in her diet, which theoretically helps her minimise her seizures. She also uses mobility aids, gets IV transfusions and goes to physical therapy.
Because of her Hemophilia, she had the lining of her uterus cauterised to prevent excessive bleeding.
But amid the pain and chaos, Hamm has found happiness and has a positive outlook on life. She thoroughly enjoys going to Disneyland.
"I am a pass holder and Disney has a lot of great accommodations for disabled people and it's fun to escape it all at the happiest place on Earth," she said. "When I spend most of my days at home extremely sick, it's nice to get a break from it all at Disney."
BioMarin: Roctavian For Hem A Likely To Patients By End Of Summer
The approval by the U.S. Food and Drug Administration (FDA) of BioMarin Pharmaceutical's Roctavian (valoctocogene roxaparvovec-rvox) late last month means that eligible adults with severe hemophilia A will soon have access to a gene therapy for the first time.
"Adults with severe hemophilia A live with several limitations, including … a high risk of health complications," Hank Fuchs, MD, president of worldwide research and development at BioMarin, said in a written Q&A with Hemophilia News Today.
"As a one-time, single-dose treatment, Roctavian has the potential to transform care for eligible adults with severe hemophilia A," Fuchs said.
Roctavian is now being manufactured at a site in California that is "one of the largest gene therapy manufacturing facilities of its kind," according to Fuchs. The therapy will become commercially available at the end of August — two months following its approval in the U.S.
"Because there are several steps required from the time a patient expresses interest until that person receives treatment with Roctavian, we anticipate that is the earliest we'd begin to see patients being treated commercially," Fuchs said.
One-time Roctavian treatment expected to replace prophylaxisRoctavian works to supply hemophilia A patients with a functional version of the F8 gene via a single, into-the-vein (intravenous) infusion. Mutations in this gene cause hemophilia A patients to lack factor VIII, known as FVIII, a key blood clotting protein.
By giving patients a healthy version of the gene encoding FVIII, Roctavian "addresses the underlying root cause of hemophilia, enabling people with severe hemophilia A to produce their own FVIII," Fuchs explained.
Typically, hemophilia A patients rely on regular infusions of FVIII replacement therapy or other prophylactic treatments to prevent bleeds.
"We know that many patients have difficulty keeping up with the burden of chronic therapy," Fuchs noted. For these patients, the one-time gene therapy offers "the possibility of freedom from years of prophylaxis [preventive treatment] that can require weekly injections or infusions."
Still, gene therapies come with a high price, and are considered to be among the most expensive medical treatments in the world.
Roctavian's list price will be $2.9 million, based on the weight of a typical patient, according to Andrew Villani, executive director of product communications and media at BioMarin.
For reference, Hemgenix, a gene therapy for hemophilia B that was approved in the U.S. In November 2022, and granted approval in Europe in February, has a list price of about $3.5 million.
But in light of the fact that Roctavian only requires a one-time infusion and appears highly effective, the gene therapy still "brings value to individuals and healthcare systems," Villani said.
We set a price that both captures the value of Roctavian and results in material savings to the healthcare system.
To give perspective, Villani noted that standard-of-care hemophilia treatment costs about $800,000 per year for a typical patient. That means that in about four years, the cost of routine preventive therapy already exceeds the one-time cost of Roctavian.
"We set a price that both captures the value of Roctavian and results in material savings to the healthcare system," Villani said.
Given its cost, some insurance companies might be hesitant to offer overage. To generate confidence from insurance companies in Roctavian's value, BioMarin is offering an outcomes-based warranty to both public and private insurers.
That means that the company would reimburse insurers by up to 100% should a patient fail to respond to the gene therapy or stop responding to it in the first four years following dosing.
BioMarin believes such a program "will help enable the greatest number of eligible patients to receive treatment," according to Villani. "We have been working with payers to educate them on the clinical and economic value to help drive coverage as soon as possible following launch. "
Patients looking for additional support on accessing Roctavian can reach out to BioMarin Rare Connections for more information.
Hem A gene therapy 1st to be approved in USRoctavian's approval in the U.S. Had been years in the making. BioMarin first applied for clearance of the gene therapy about 3.5 years ago, based on three-year data from a Phase 1/2 dose escalation study (NCT02576795). That application also included six-month interim findings from the ongoing pivotal Phase 3 GENEr8-1 trial (NCT03370913), which is slated to run through November 2024. GENEr8-1 enrolled 134 men with severe hemophilia A on routine preventive treatment.
Upon the FDA's request, BioMarin resubmitted the application with two-year findings from GENEr8-1 in 2022, prompting the agency to additionally request three-year data. That data, which became available this year, backed the FDA's eventual approval of Roctavian last month.
Three-year data showed that participants had an 82.9% reduction in bleeds that required treatment compared with the period before the trial. Most participants had not experienced any clinically relevant bleeds, and 92% were able to stop using preventive treatments, the data showed.
FVIII activity remained high, and patients were able to lower their use of FVIII replacement therapy by 96.8%.
"Most study participants continued to respond to treatment through year three and beyond, without supplemental use of regular prophylaxis," Fuchs said.
To best understand why those findings are meaningful, "it's important first to acknowledge how devastating untreated hemophilia is and what patients were up against," Fuchs said.
According to Fuchs, when left untreated, hemophilia patients will bleed without cause about 30-60 times per year. In the long term, bleeds can lead to joint damage and immobility, or become life-threatening.
"For patients that live with this disease on a daily basis, a treatment like Roctavian may address significant unmet needs … by way of fewer bleeds, without the burden of chronic therapies," Fuchs said, adding, "Our hope is that these people can live life more fully and engage in activities they enjoy, like traveling or spending time with their family."
Patients given gene therapy will be followed for up to 15 yearsWhile it's not known for certain whether the treatment's effects will wane over time, patients in the Phase 1/2 trial have now been followed for more than six years.
Findings to date indicate that most patients are still off preventive therapy, which "may provide insight into the longevity of response," Fuchs noted.
To learn more about Roctavian's effects over the long term, GENEr8-1 participants will continue to be monitored for up to 15 years. A post-approval, real-world study will similarly follow patients for 15 years or more.
A number of other clinical studies also are ongoing to evaluate the potential use of Roctavian across different patient populations.
Specifically, two Phase 1/2 trials are underway to investigate Roctavian's safety and effectiveness in patients who have antibodies against AAV5, the therapy's viral carrier (NCT03520712), or who have neutralizing antibodies, or inhibitors, against FVIII (NCT04684940).
The presence of these antibodies could potentially compromise the therapy's effectiveness. Hemophilia A patients who have these inhibitors were not included in GENEr8-1 and thus are not now eligible to receive treatment with Roctavian. All patients are screened for these antibodies prior to being given the infusion.
Patients also must be screened for liver health prior to receiving the gene therapy. Most patients in GENEr8-1 required the use of corticosteroids to combat elevations in certain liver enzymes that were observed after they received treatment. Individuals with pre-existing liver problems will need to consult a specialist to see if they are eligible to receive Roctavian.
BioMarin looking to expand access to RoctavianAnother open-label Phase 3b trial, called GENEr8-3 (NCT04323098), is investigating the use of Roctavian when given alongside anti-inflammatory corticosteroids.
According to Fuchs, BioMarin will provide data for these studies as it becomes available, "building on what already constitutes the largest clinical data package for gene therapy in hemophilia."
"We look forward to sharing the findings of these studies and their implications on Roctavian's eligibility population," Fuchs said, but noted that it is too soon to speculate as to whether these studies will affect regulatory decisions about who is eligible to receive the hem A gene therapy.
Roctavian has earned conditional approval in the European Union for adults with severe hemophilia A who do not have antibodies against AAV5 or FVIII inhibitors. Conditional approval means that while the company can market a therapy, more data are still required by regulatory authorities to confirm its clinical benefits.
The conditional approval, granted last year, was based largely on two-year data from the GENEr8-1 trial, as well as six-year data from the Phase 1/2 trial.
According to Fuchs, conversion to a full approval "will be contingent on the provision of additional data from currently ongoing Roctavian clinical studies, including longer-term follow up of patients enrolled in the pivotal trial GENEr8-1."
"We are continuing to engage with regulatory agencies around the world with the goal of expanding access to Roctavian," Fuchs said.
"On behalf of all of us at BioMarin, I would like to thank the community — individuals living with hemophilia, as well as their caregivers and the healthcare providers whose contributions led to the development and approval of Roctavian," he said.
$2.9 Million Gene Therapy For Severe Hemophilia Is Approved By FDA
WASHINGTON -- U.S. Officials on Thursday approved drugmaker BioMarin's gene therapy for the most common form of hemophilia, a $2.9 million infused treatment that can significantly reduce dangerous bleeding problems.
The Food and Drug Administration approved Roctavian for adult patients with severe cases of hemophilia A, the inherited blood-clotting disorder that can lead to bleeding after minor injuries or scrapes. It's the first gene therapy for those patients.
The IV therapy is a long-awaited alternative to current treatments, including weekly doses of a protein needed to help blood clot. Some patients take a newer, longer-acting biotech drug that replaces the protein.
BioMarin said in a statement that the FDA approval was based on a three-year study showing a 50% reduction in annual bleeding incidents among 134 patients who received the treatment. Most patients continued to respond to the treatment beyond three years, without needing regular IV infusions, the company said.
BioMarin said Roctavian's $2.9 million price tag reflects "the possibility of freedom from years" of infusions, which cost about $800,000 annually for a typical patient. The price is less than the $3.5 million announced last year for a similar gene therapy for hemophilia B, a less common form of the disease.
Like most medicines in the U.S., the new treatment will mainly be paid for by insurers, not patients.
BioMarin said it estimates about 2,500 U.S. Patients will be eligible to receive the therapy under the terms of the FDA's approval. Patients with certain underlying health problems and conditions are excluded under the prescribing information.
Hemophilia is caused by mutations that prevent the production of proteins needed for blood clotting. Hemophilia A is the most severe variant of the condition, and some patients can experience spontaneous bleeding even without any injury. Left untreated, the condition can cause bleeding that seeps into joints and organs, including the brain.
Roctavian uses an inactivated virus, created in a lab, to deliver a replacement gene to the liver cells that produce the clotting protein. When the therapy is successful, patients can then produce the protein themselves. The label warns that rare, severe allergic reactions can occur.
Dr. Margaret Ragni called Roctavian "a major improvement in terms of reducing the burden of disease." But she notes that many patients are comfortable with their current treatments and may be hesitant to try a new gene therapy.
"I think there's a group that will want to do this, but patients need to hear what the risks and benefits are," said Ragni, who treats patients at the Hemophilia Center of Western of Pennsylvania in Pittsburgh.
BioMarin was among the first companies to begin testing an experimental gene therapy in patients more than six years ago.
The San Rafael, California-based company excluded patients with certain potentially complicating conditions, including liver disorders and resistance to the standard blood clotting protein, which often develops in some hemophilia patients. BioMarin's president for research and development, Dr. Henry Fuchs, said the company is conducting studies in some of those excluded groups to see if they can safely receive the therapy.
Another key question is how long the therapy's benefits last. BioMarin has followed the patients for more than three years and they continue to experience reduced bleeding. But levels of the clotting protein in the bloodstream fall over time, suggesting additional treatments may eventually be needed.
"Let's make sure the expectation isn't that this is taken one time, forever and it will work perfectly for the rest of your life," Fuchs said, adding "at some point we'll know a lot more about durability."
Roctavian was approved in Europe last August, but the therapy has faced pushback from government health programs over its cost.
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute's Department of Science Education. The AP is solely responsible for all content.
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