Wednesday, August 30, 2017

APF is #Houston Strong!

The American Porphyria Foundation office located in Houston, TX remains closed due to the extreme flooding from Hurricane Harvey. All office staff are safe. Please continue to contact us with any needs as we will be checking voicemail and email on a regular basis. We will inform you when the office has re-opened. For those with questions that need to be answered with urgency please contact Desiree Lyon, Executive Director at 713.857.0995. Thank you.
WOODWAY DRIVE - Directly across the street from where the APF office is located.

NIH Part 1 101 on Porphyrias (Updated Info)

Part 1


What are porphyrias?

Porphyrias are rare disorders that affect mainly the skin or nervous system and may cause abdominal pain. These disorders are usually inherited, meaning they are caused by abnormalities in genes passed from parents to children. When a person has a porphyria, cells fail to change body chemicals called porphyrins and porphyrin precursors into heme, the substance that gives blood its red color. The body makes heme mainly in the bone marrow and liver. Bone marrow is the soft, spongelike tissue inside the bones; it makes stem cells that develop into one of the three types of blood cells—red blood cells, white blood cells, and platelets.
The process of making heme is called the heme biosynthetic pathway. One of eight enzymes controls each step of the process. The body has a problem making heme if any one of the enzymes is at a low level, also called a deficiency. Porphyrins and porphyrin precursors of heme then build up in the body and cause illness.

What is heme and what does it do?

Heme is a red pigment composed of iron linked to a chemical called protoporphyrin. Heme has important functions in the body. The largest amounts of heme are in the form of hemoglobin, found in red blood cells and bone marrow. Hemoglobin carries oxygen from the lungs to all parts of the body. In the liver, heme is a component of proteins that break down hormones, medications, and other chemicals and keep liver cells functioning normally. Heme is an important part of nearly every cell in the body.

What are the types of porphyria?

Each of the eight types of porphyria corresponds to low levels of a specific enzyme in the heme biosynthetic pathway. Experts often classify porphyrias as acute or cutaneous based on the symptoms a person experiences:
  • Acute porphyrias affect the nervous system. They occur rapidly and last only a short time.
  • Cutaneous porphyrias affect the skin.
Two types of acute porphyrias, hereditary coproporphyria and variegate porphyria, can also have cutaneous symptoms.
Experts also classify porphyrias as erythropoietic or hepatic:
  • In erythropoietic porphyrias, the body overproduces porphyrins, mainly in the bone marrow.
  • In hepatic porphyrias, the body overproduces porphyrins and porphyrin precursors, mainly in the liver.
Table 1 lists each type of porphyria, the deficient enzyme responsible for the disorder, and the main location of porphyrin buildup.
Table 1. Types of porphyria
Type of PorphyriaDeficient EnzymeMain Location of Porphyrin Buildup
delta-aminolevulinate-dehydratase deficiency porphyriadelta-aminolevulinic acid dehydrataseliver
acute intermittent porphyriaporphobilinogen deaminaseliver
hereditary coproporphyriacoproporphyrinogen oxidaseliver
variegate porphyriaprotoporphyrinogen oxidaseliver
congenital erythropoietic porphyriauroporphyrinogen III cosynthasebone marrow
porphyria cutanea tardauroporphyrinogen decarboxylase (~75% deficiency)liver
hepatoerythropoietic porphyriauroporphyrinogen decarboxylase (~90% deficiency)bone marrow
erythropoietic protoporphyria*ferrochelatase (~75% deficiency)bone marrow

How common is porphyria?

The exact rates of porphyria are unknown and vary around the world. For example, porphyria cutanea tarda is most common in the United States, and variegate porphyria is most common in South America.1

What causes porphyria?

Most porphyrias are inherited disorders. Scientists have identified genes for all eight enzymes in the heme biosynthetic pathway. Most porphyrias result from inheriting an abnormal gene, also called a gene mutation, from one parent. Some porphyrias, such as congenital erythropoietic porphyria, hepatoerythropoietic porphyria, and erythropoietic protoporphyria, occur when a person inherits two abnormal genes, one from each parent. The likeliness of a person passing the abnormal gene or genes to the next generation depends on the type of porphyria.
Porphyria cutanea tarda is usually an acquired disorder, meaning factors other than genes cause the enzyme deficiency. This type of porphyria can be triggered by
  • too much iron
  • use of alcohol or estrogen
  • smoking
  • chronic hepatitis C—a long-lasting liver disease that causes inflammation, or swelling, of the liver
  • HIV—the virus that causes AIDS
  • abnormal genes associated with hemochromatosis—the most common form of iron overload disease, which causes the body to absorb too much iron
For all types of porphyria, symptoms can be triggered by
  • use of alcohol
  • smoking
  • use of certain medications or hormones
  • exposure to sunlight
  • stress
  • dieting and fasting

What are the symptoms of porphyria?

Some people with porphyria-causing gene mutations have latent porphyria, meaning they have no symptoms of the disorder. Symptoms of cutaneous porphyrias include
  • oversensitivity to sunlight
  • blisters on exposed areas of the skin
  • itching and swelling on exposed areas of the skin
Symptoms of acute porphyrias include
  • pain in the abdomen—the area between the chest and hips
  • pain in the chest, limbs, or back
  • nausea and vomiting
  • constipation—a condition in which an adult has fewer than three bowel movements a week or a child has fewer than two bowel movements a week, depending on the person
  • urinary retention—the inability to empty the bladder completely
  • confusion
  • hallucinations
  • seizures and muscle weakness
Symptoms of acute porphyrias can develop over hours or days and last for days or weeks. These symptoms can come and go over time, while symptoms of cutaneous porphyrias tend to be more continuous. Porphyria symptoms can vary widely in severity.

How is porphyria diagnosed?

A health care provider diagnoses porphyria with blood, urine, and stool tests. These tests take place at a health care provider’s office or a commercial facility. A blood test involves drawing blood and sending the sample to a lab for analysis. For urine and stool tests, the patient collects a sample of urine or stool in a special container. A health care provider tests the samples in the office or sends them to a lab for analysis. High levels of porphyrins or porphyrin precursors in blood, urine, or stool indicate porphyria. A health care provider may also recommend DNA testing of a blood sample to look for known gene mutations that cause porphyrias.

How is porphyria treated?

Treatment for porphyria depends on the type of porphyria the person has and the severity of the symptoms.

Acute Porphyrias

A health care provider treats acute porphyrias with heme or glucose loading to decrease the liver’s production of porphyrins and porphyrin precursors. A patient receives heme intravenously once a day for 4 days. Glucose loading involves giving a patient a glucose solution by mouth or intravenously. Heme is usually more effective and is the treatment of choice unless symptoms are mild. In rare instances, if symptoms are severe, a health care provider will recommend liver transplantation to treat acute porphyria. In liver transplantation, a surgeon removes a diseased or an injured liver and replaces it with a healthy, whole liver or a segment of a liver from another person, called a donor. A patient has liver transplantation surgery in a hospital under general anesthesia. Liver transplantation can cure liver failure. More information is provided in the NIDDK health topic, Liver Transplantation.

Cutaneous Porphyrias

The most important step a person can take to treat a cutaneous porphyria is to avoid sunlight as much as possible. Other cutaneous porphyrias are treated as follows:
  • Porphyria cutanea tarda. A health care provider treats porphyria cutanea tarda by removing factors that tend to activate the disease and by performing repeated therapeutic phlebotomies to reduce iron in the liver. Therapeutic phlebotomy is the removal of about a pint of blood from a vein in the arm. A technician performs the procedure at a blood donation center, such as a hospital, clinic, or bloodmobile. A patient does not require anesthesia. Another treatment approach is low-dose hydroxychloroquine tablets to reduce porphyrins in the liver.
  • Erythropoietic protoporphyria. People with erythropoietic protoporphyria may be given beta-carotene or cysteine to improve sunlight tolerance, though these medications do not lower porphyrin levels. Experts recommend hepatitis A and B vaccines and avoiding alcohol to prevent protoporphyric liver failure. A health care provider may use liver transplantation or a combination of medications to treat people who develop liver failure. Unfortunately, liver transplantation does not correct the primary defect, which is the continuous overproduction of protoporphyria by bone marrow. Successful bone marrow transplantations may successfully cure erythropoietic protoporphyria. A health care provider only considers bone marrow transplantation if the disease is severe and leading to secondary liver disease.
  • Congenital erythropoietic porphyria and hepatoerythropoietic porphyria. People with congenital erythropoietic porphyria or hepatoerythropoietic porphyria may need surgery to remove the spleen or blood transfusions to treat anemia. A surgeon removes the spleen in a hospital, and a patient receives general anesthesia. With a blood transfusion, a patient receives blood through an intravenous (IV) line inserted into a vein. A technician performs the procedure at a blood donation center, and a patient does not need anesthesia.

Secondary Porphyrinurias

Conditions called secondary porphyrinurias, such as disorders of the liver and bone marrow, as well as a number of drugs, chemicals, and toxins are often mistaken for porphyria because they lead to mild or moderate increases in porphyrin levels in the urine. Only high—not mild or moderate—levels of porphyrin or porphyrin precursors lead to a diagnosis of porphyria.

Friday, August 25, 2017

Biotech AHP News

Alnylam heads for phase 3 with acute porphyria program
by Phil Taylor | 
Jun 26, 2017 10:25am

Alnylam porphyria drug reduces annualized relapse rate by 73% in phase 1 study.
RNA interference (RNAi) specialist Alnylam has hit the accelerator on its candidate drug for ultrarare porphyria diseases, prepping for phase 3 trials later this year after unveiling initial results in 12 patients.
Alnylam's givosiran achieved a dramatic reduction in annual attack rates in the phase 1 trial reported at the International Congress on Porphyrins and Porphyrias in Bordeaux, France, and could become the first drug to be approved for preventing attacks, according to the biotech.
It's a needed boon for Alnylam, which was hit hard last year after it was forced to drop its hereditary ATTR amyloidosis drug revusiran. More patient deaths were seen on that drug versus placebo in the late-stage ENDEAVOUR trial, forcing a switch to new lead drug patisiran.
Porphyrias are a group of disorders that result from a build-up of substances—called porphyrins—that can damage organs and the nervous system. As the name suggests, acute hepatic porphyrias damage the liver, and are among the most common forms of the disease, but are still very uncommon. Taken together, all forms of porphyria afflict fewer than 200,000 people in the U.S., according to the American Porphyria Foundation (APP).
The most common symptom is intense abdominal pain, but some people also suffer muscular weakness, sensory disturbances or convulsions, and as a group the diseases are "devastating for patients" with attacks lasting for days and often requiring admission to hospital, according to Akshay Vaishnaw M.D., Ph.D., Alnylam's head of R&D, who discussed the data on a conference call this morning.
At the moment, the only drug approved for use in porphyria is hemin, which is labeled as a treatment for attacks but is given off-label to some patients for prevention. Intravenous glucose therapy is also used, but both treatments have limited activity in preventing or hastening recovery from attacks, according to the APP.
Enter givosiran, a gene-silencing drug designed to switch off the aminolevulinic acid synthase 1 (ALAS1) gene. The drug reduces levels of two porphyrin precursors (ALA and PBG), which researchers hope will prevent attacks.
The RNAi switched off ALAS1 in the trial and achieved a 73% reduction (PDF) in annualized attack rate compared to placebo in the 12-patient phase 1 trial, with a 73% reduction in annualized hemin doses. Clinicians have suggested a 30% reduction in attacks would be clinically meaningful, according to Barry Greene, president of Alnylam.
Importantly, the reduction in attacks appeared to be dose-dependent and matched reductions in ALA/PBG levels, suggesting these could be used as biomarkers for the drug's activity in future studies, said Vaishnaw.  There was one death among patients in the treatment group (due to hemorrhagic pancreatitis) as well as three other serious adverse events that the investigators concluded were not linked to the study drug.
Data from an eight-patient open-label extension study found a further reduction in attacks and suggested control could be better with longer-term dosing, said Vaishnaw, although he stressed the results are still preliminary with such a small patient cohort. That said, there is no evidence for this with hemin, but some data suggest that control gets worse in hemin-treated patients over time, he added.
Either way, "there is no question these annualized attack rate reductions have a big impact on the lives of patients," said Vaishnaw on the conference call.
"We are very encouraged by the data … and the potential for the givosiran program," said Greene, noting that the drug could offer a once-monthly, low-volume subcutaneous injection therapy for patients with porphyrias.
On the thorny topic of pricing, Alnylam is thinking ahead and already reckons it can make a big impact on the costs of acute hepatic porphyrias. Treatment currently costs between $400,000 and $650,000 per patient per year, according to a natural history study (EXPLORE) due for presentation at the ICPP meeting on Wednesday
The phase 3 program will get underway in the fourth quarter and focus on attack rates—the most devastating element of the disease—said Alnylam. It will, however, also include a pharmacoeconomic analysis to take into account direct healthcare costs as well as indirect factors such as loss of work days, etc.

Alnylam—which said it plans to self-develop and commercialize the drug—has already secured breakthrough registration for the drug in the U.S. and PRIME (priority medicine) status in the E.U., so if the phase 3 program goes well, givosiran is in line for speedy review by regulators.

Wednesday, August 23, 2017

A Little Bit Of History of Porphyria

Medical Moment~ History of Porphyria

A Little Bit of History

1841 - The term ‘porphyrin comes from the Greek word, porphyus, meaning reddish-purple. It was first thought that the reddish color of blood was from iron. One early scientist performed an experiment to prove that this was not the case. He washed dried blood with concentrated sulfuric acid to free the iron. He then treated it with alcohol and the resulting iron free residue took on a reddish purple color though it contained no iron compound

1844 - Gerardus Johannes Mulder determined the chemical composition of this purplish, iron free substance, which he named "hematin," He also illustrated that hematin took up oxygen.

1867 - J.L.W. Thudichum described the beautiful spectrum and fluorescence of these red porphyrins after he published his first book on the analysis of urine.
1871 - Felix Hoppe-Seyler crystallized hematin and described its spectrum. He then demonstrated that the crystalline form differed from one animal species to another. Using his own newly constructed gas pump, he found that oxygen formed a loose, dissociable compound with hemoglobin, which he called "oxyhemoglobin." He renamed the iron free hematin ‘hematoPorphyrin’.

1874 - Dr. J.H. Schultz described a case of a 33-year-old male weaver who suffered from skin sensitivity, an enlarged spleen and reddish urine since he was an infant. He called the condition pempigus leprosus. His was most likely the first description of protoporphyria. Dr. Schultz was later credited with giving the disease its name.

1880 - MacMunn described a patient’s dark reddish urine of a patient with symptoms of an attack of acute Porphyria.

1888 - Shortly after, sulphonal was introduced as a hypnotic drug, Joseph Stokvis had a patient who, after taking the drug, excreated the tell-tale dark reddish urine typical of porphyria. The elderly woman then became paralyzed and died. Stokvis deducted that the pigment in her urine was the hematoporphyrin.

1889 - B.J.Stokvis published the first case and clinical description of acute hepatic porphyria.

1890 - George Harley (1829-96) studied a 27-year-old who also excreted reddish urine and an "unusual nerve disturbance after taking sulphonal.

1898 - T.McCall Anderson described two brothers had eruptions with burning and pruitus on the sun exposed areas of their skin so severe that they lost part of their ears and nose. They exhibited dark urine.

1898 - Alfred F. Harris demonstrated that the urine of both brothers contained the hematoporphyrin group.

1906 - Dr. Max Dobrschansky described the first case of acute porphyria after a patient had a barbiturate.

1911 - H. Gunther classified the diseases of porphyria, including congenital erythropoietic porphyria (CEP), which he called congenital hepatoporphyria, the rarest porphyria.

1913 - Dr. Friedrich Meyer Betz injected himself with hematoporphyrins to determine their photodynamic impact. He subjected himself to the sun and became so photosensitized that the extremely painful photosensitive effect lasted several months. The photos of Dr. Betz taken hours after he injected himself illustrated his badly swollen face. He was unrecognizable until the swelling decreased. The-experiment is used today in dermatology text books. View these photos on the APF website.

1915 - Hans Fischer studied one of H. Gunther’s patients, Mr. Petry, who had the rare type of Porphyria, CEP. Using data from Mr. Petry’s case, Fischer provided significant insight into the chemistry of porphyrins. He also found that uroporphyrins and coproporphyrins were different from hematoporphyrins and subsequently suggested that the hemato prefix be dropped.

1923 - A. E. Garrod credits H. Gunther with first recognizing that hematoporphyria was, in fact, an inherited metabolic problem in his manuscript, Inborn Errors of Metabolism. This is the first time the term "inborn errors" of metabolism had been ever used for a group of inherited metabolic disorders and the year CEP was first identified.

1937 Dr. Jan G. Waldenstrom suggested that the name of the diseases of porphyrin metablolism be porphyrias rather than Hematoporphyrias. Using Paul Ehrlich’s aldehyde reagent, Waldenstorm identified 103 patients with acute porphyria by testing their urine and noting the red color. He discovered that asymptomatic family members of these patients also had the same reaction if they ingested even small amounts of barbiturates and sulphonal.

1949 -Dr. Cecil J. Watson identified cases in which there were excessive amounts of coproporphyrins in the stool and urine and suggested that this was caused by an inborn error of metabolism. He continued his research in the United States, where he and Dr. Samuel Schwartz discovered a fundamental test, the "Watson-Schwartz tests".

1954 - R. Schmid, Samuel Schwartz and Cecil. J. Watson classified the porphyrias according to the porphyrin content in the bone marrow and liver.

1955 - A. Goldberg and H. Berger showed that individuals with an excess of coproporphyrin had another inherited form of porphyria that they called hereditary coproporphyria. HCP is an autosomal dominant form of hepatic porphyria that is very similar to acute intermittent porphyria, except that some patients develop skin photosensitivity, too.

1960's – Earnest Porphyria research in Europe and US.

1961 - Heinrich Gustav Magnus described erythropoietic protoporphyria (EPP) as a genetic disorder arising from impaired activity of ferrochelatase, which is what adds iron to protoporphyrin to form heme.

1970-2011 - Drs. Anderson, Desnick, Bissell, Bloomer, Bonkovsky,, Bottomley, Dailey, Galbraith, ,Kappas, Kreimer-Birnbaum, Kushner, Lamon, Levere, Levine, Mathews-Roth, McDonaugh, Nichols, Peters, Sinclair, Pimstone, Pierach, Poh-Fitzpatrick, Sassa, Shedlofsky, Schmid, Sassa, Tishler, Tschudy, Watson,, Phillips and many others too numerous to name have furthered porphyria research and have bettered the health care of all of us with Porphyria. We owe all these people a great debt and a great measure of thanks.

2008-2011- The APF Protect the Future program to train the next generation of experts was initiated. We are grateful for the newest experts; Drs. Manisha Balwani, Lawrence Lui, Gagen Sood, Manish Thapar, Bradley Freilich, Charles Lourenco, Brenden McGuire, Bruce Wang, Majid Rizk, Guiherme Perini, Jennifer Guy, Jeffery Wickliffe, Aswani Singal, Sajid Mittal,Charles Parker.

Monday, August 21, 2017

EPP Have you ever wondered why you have been sunburnt on a cloudy day?

Have you ever wondered why you have been sunburnt on a cloudy day?
The total dose of UV radiation reaching the earth’s surface and hence, the potential damage to human skin and tissues, varies, depending on many factors.
The sun’s elevation in the sky depends on the time of the day and year. The shorter the distance that photons (making up the total of UV radiation) need to travel though the earth's atmosphere, the greater the intensity of UV radiation. The altitude of a location also effects UV radiation levels as the higher a location is above sea level, the shorter the distance UV radiation travels.
The thinning of the ozone layer located above Antarctica has had a considerable impact on the ability of the atmosphere to absorb UVB, a significant contributor to the increased incidence of skin cancer and other damage to human tissues which has been observed in populations bordering the ozone hole.
Clouds act on UV primarily by scattering radiation which can both reduce and enhance the UV radiation levels depending on the type of cloud cover.
Some clouds absorb infrared radiation and as a result of the diminished heat sensation, people are given a false sense of security and often change their behaviour on cloudy days, unaware that they are exposing themselves to this potential danger.
UV radiation is also reflected from surfaces such as sand, snow and water. These surfaces can increase the UV radiation at ground level and increase the amount of skin damage incurred from UV radiation exposure.
So, when all these factors are considered, it is important to recognise that the net potential UV risk is a result of these associated variables, depending an Individual’s circumstances. The only sure way to significantly reduce the risk of skin damage is with vigilant protection from UV radiation and light, known as photoprotection.

Thursday, August 17, 2017

EPP is CLINUVEL's lead clinical indication for SCENESSE®(afamelanotide 16mg)

EPP is CLINUVEL's lead clinical indication for SCENESSE®(afamelanotide 16mg)
Clinical and regulatory progress:
In December 2014, the European Commission approved SCENESSE® to prevent phototoxicity in adult patients diagnosed with EPP, following a recommendation from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP). You can read the announcement here.
CLINUVEL is currently working to make SCENESSE® available across Europe. If you have EPP and would like to receive updates on our program, please contact us.
About Erythropoietic Protoporphyria (EPP)
EPP symptoms on the lips
EPP is a rare life-long genetic disease found mainly in fair-skinned people. It is characterised by severe phototoxicity (intolerance of light) of the skin resulting in intolerable pain, swelling and scarring, usually of exposed areas such as the face, hands and feet. Reactions can vary from mild to extreme with hospitalisation and powerful pain killers required in the worst cases.
Children and adults living with EPP must avoid sunlight and even reflected light for life, often staying indoors or wearing protective clothing. Conventional sunscreens have little to no effect.
Since sun avoidance is recommended, patients lead lives where they are in the sun for very limited time. This can prevent normal social activities and the intense pain that is experience interferes with normal daily activities and can prevent adequate sleep.
Approximately 10,000 people globally are affected by EPP, an estimated 4,000 in the US.
Keep up to date with our clinical trials, EPP blogs and videos.
 Clinical results - EPP
In January 2009 CLINUVEL announced interim results from its lead Phase III study of SCENESSE® (afamelanotide 16mg) in patients diagnosed with EPP (CUV017). The data from the first 14 Swiss patients to complete the 12 month study period were analysed, showing SCENESSE® was of clinical benefit in EPP. For more information, see the company's announcement.
In December 2009 CLINUVEL announced preliminary results from its lead Phase III study of SCENESSE® in 100 patients diagnosed with EPP (CUV017). For more information, see the company's announcement.
CLINUVEL released full results from the CUV017 study in July 2010. For more information, see the company's announcement.
In November 2011 CLINUVEL announced results from it first US Phase II study of SCENESSE® (CUV030). You can read the results here.
In December 2011 CLINUVEL announced results from its second Phase III study of SCENESSE® (CUV029). You can view the results here.
In November 2013 CLINUVEL announced results from its US Phase III study of SCENESSE® (CUV039). You can read the results here.
 Regulatory status
SCENESSE® (afamelanotide 16mg) has been granted Orphan Drug Designation by the EMA, FDA, TGA and Swissmedic for EPP.
In May 2010, the Italian Medicines Agency allowed for the prescription and reimbursement of SCENESSE® (afamelanotide 16mg) under Law 648/96 for Italian patients diagnosed with EPP. For more information, see this page.
In December 2014, the European Commission approved SCENESSE® to prevent phototoxicity in adult patients diagnosed with EPP, following a recommendation from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP). You can read the announcement here.
CLINUVEL is currently working to make SCENESSE® available across Europe. If you have EPP and would like to receive updates on our program, please contact us.

·       Harms JH, et al. ‘Mitigating photosensitivity of erythropoietic protoporphyria patients by an agonistic analog of alpha-melanocyte stimulating hormone.’ Photochem Photobiol. 2009 Nov-Dec;85(6):1434-9.
·       Murphy GM. ‘Diagnosis and Management of the Erythropoietic Porphyrias’, Dermatologic Therapy 2003;16:57-64.
·       Thunell S, Harper P, Brun A. ‘Porphyrins, Porphyrin Metabolism and Porphyrias. IV. Pathophysiology of Erythropoietic Protoporphyria - Diagnosis, Care and Monitoring of the Patient’. Scand J Clin Lab Invest 2000;60:581-604.
·       Todd DJ. ‘Clinical Implications of the Molecular Biology of Erythropoietic Protoporphyria’, J Eur Acad Dermatol Venerol 1998;11:207-13.

Monday, August 14, 2017

New Positive Clinical Results for Givosiran (ALN-AS1) in Acute Intermittent Porphyria Patients with Recurrent Attacks

26 Jun, 2017New Positive Clinical Results for Givosiran (ALN-AS1) in Acute Intermittent Porphyria Patients with Recurrent Attacks
We reported interim results from our ongoing Phase 1 study with givosiran at the 2017 International Congress on Porphyrins and Porphyrias (ICPP), held June 25 – 28, 2017 in Bordeaux, France. Data presented were from the first three unblinded cohorts from Part C, in patients with acute intermittent porphyria (AIP) that experience recurrent attacks and initial data from the open-label extension (OLE) study.
Read our press release
View the complete Phase 1 interim and OLE data presentation
View the results from the EXPLORE natural history study
View the poster on healthcare utilization and costs
View the poster on disease burden in patients with AIP and recurrent attacks

Patients treated with givosiran (N=9) experienced a mean 63 percent reduction in the annualized number of all porphyria attacks relative to the run-in period attack rate, with consistent effects observed across a wide range of baseline attack rates. Evaluating only attacks that were treated at a healthcare facility or with hemin, givosiran administration was associated with a mean 73 percent reduction in annualized attack rate relative to placebo during the treatment period. A 73 percent mean decrease in annualized hemin doses relative to the run-in period was also reported. Additionally, in a new analysis, the observed reduction in annualized attack rate was found to be associated with the degree of ALA and PBG lowering.
Further, initial results from Cohorts 1 and 2 (N=8) of the givosiran OLE study were also presented; to date, all eligible patients have rolled over from the Phase 1 study to the OLE study. These data showed that that longer-term treatment with givosiran was associated with consistent reductions in the annualized porphyria attack rate.
Importantly, as of the data cutoff date, givosiran administration was generally well tolerated in recurrent attack AIP patients in Cohorts 1-3 in Part C of the Phase 1 study and in Cohorts 1 and 2 of the ongoing OLE study, with a mean of 169 and 111 days on study, respectively, and up to 12 months on givosiran. In Part C there were no drug-related serious adverse events (SAEs) or discontinuations due to adverse events (AEs). Excluding porphyria attacks, three patients had four SAEs; none were assessed as related to study drug. As previously reported, one death occurred in a patient in cohort 3 in the givosiran arm due to hemorrhagic pancreatitis complicated by a pulmonary embolism and following a recent hospitalization for bacteremia; the death was considered to be unlikely related to study drug by the investigator and the study’s Safety Review Committee. During the Phase 1 treatment period, all randomized patients reported at least one AE.
The majority of AEs were assessed as mild or moderate in severity. Twenty-five percent of patients had severe AEs, assessed as unrelated to study drug. AEs in three or more patients included: abdominal pain, headache, nasopharyngitis, nausea and vomiting. Four patients were assessed as having AEs possibly related to study drug, including injection site reaction (mild and self-limiting), hypersensitivity, myalgia, headache, moderate renal impairment (in a patient with a history of moderate renal impairment) and erythema. There were no other clinically significant changes in vital signs, electrocardiograms, clinical laboratory parameters (including liver function tests and lipase tests), or physical examination. The overall safety experience in the ongoing OLE study was consistent with results from the Phase 1 study. No SAEs (excluding porphyria attacks) or discontinuations due to AEs have been reported in the OLE study.
Separately, updated 12-month data from EXPLORE – a prospective, multinational, observational study characterizing the natural history and clinical management of acute hepatic porphyria (AHP) patients with recurrent attacks or who receive hemin prophylaxis to prevent attacks – demonstrate that patients suffer from both acute attacks and chronic symptoms in between attacks, that together result in a diminished quality of life. The annualized attack rate on study was approximately 5 attacks per person with a mean attack duration of 7 days. The majority of attacks (77 percent) required treatment in the hospital, urgent healthcare facility or with intravenous hemin.
Further, in the first analysis of its kind for AHP in the U.S., an analysis of direct costs associated with AHP and recurrent attacks revealed the average estimated annual expenditure per patient ranges from approximately $400,000 to $650,000 of direct costs.

We believe these latest datasets further support givosiran’s potential to transform the treatment of patients suffering from acute hepatic porphyrias, and we look forward to continuing our efforts in rapidly developing givosiran towards regulatory filings and, if approved, to patients.

Wednesday, August 9, 2017

Holly Hamilton joins the APF CEP Facebook group

Welcome Holly Hamilton as our new Moderator the the Closed Facebook CEP group.  Holly and her husband Justin are wonderful parents and folks.  Justin & Holly are the proud parents of 2 adorable children.

They also support the American Porphyria Foundation and spreading awareness.

To learn more about Justin & Holly and how they manage Justins CEP together catch the interview at this link:

To learn more about CEP:

To join the CEP FB Group:

                      Thank you for supporting the APF!

Friday, August 4, 2017


IMPORTANT!!! A new research study is starting for PCT. The Harvoni Treatment for Porphyria Cutanea Tarda study is Beginning to recruit patients now. Please contact the APF office on 1-866-APF-3635 to find out how to participate.
                                 Remember~ "Research is your key to a cure"

What is δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)?

What is δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)? ADP is more severe than the other acute porphyrias and can present in childhoo...