The effectiveness of PANHEMATIN for the amelioration of recurrent attacks of acute intermittent porphyria was evaluated in five open-label studies, one compassionate-use study, case reports, and an observational study investigating patient reported outcomes in patients with acute porphyrias.

Open-Label Studies

In the initial 5 open-label studies,1-5 99 patients with acute porphyrias (72 with AIP) were treated with 3-4 mg/kg/day of hemin once or twice daily. Of the 99 patients in these studies, 30 received prior or concomitant glucose administration. Patients experienced a clinical response in 85.5% (141/165) of treatment courses (Figure 1). Clinical response was defined by improvement of symptoms and reduction in pain. All patients experienced a chemical response which was defined as normalization of urinary aminolevulinic acid (ALA) and porphobilinogen (PBG).

Watson et al.1 studied the use of hemin treatment in 15 patients with acute porphyrias, of whom 11 were with AIP. Seven patients were female and four were male with an age range of 19-45 years with biochemical evidence of AIP. Preparations of 4 mg/ kg IV of hemin were infused at 12- or 24-hour intervals for 1 to 4 days after trials of glucose of various durations and dosages in all patients. All patients, with exception of one, experienced a clear clinical response most of which was rapid after hemin infusion. All patients also demonstrated a chemical response based on 58%-100% reduction in urinary ALA and PBG levels.

Pierach et al.2 examined the use of 2 to 4 mg/kg of hemin IV in 57 patients with acute porphyrias, of whom 43 were with AIP. Out of 82 individual acute intermittent porphyria attacks with 476 hemin infusions (82 treatment courses) administered, a clinical response was seen in 74 (90%) acute attacks. A chemical response was seen for those patients who had elevated urinary ALA and PBG levels prior to hemin treatment.

McColl et al.3 reported the use of 4 mg/kg of hemin IV given either every 12 or 24 hours for three to five days in the treatment of 13 attacks of acute porphyria in eight patients. Seven of these 8 patients had AIP. Five patients with AIP were female and two were male with a mean age of 25 years (range 19-31 years). All patients had biochemical and clinical evidence of an attack of acute porphyria at the time of hemin administration. All patients had a chemical response of approximately 50% reduction in urinary ALA and PBG from pre-treatment values. In addition, clinical response was seen after hemin treatment in a total of 7 attacks in 5 AIP patients.

Lamon et al.4 reported on 12 patients with acute porphyrias, of whom 11 were with AIP. These AIP patients received 190 infusions of approximately 2 to 4 mg/kg of hemin IV given every 12 or 24 hours for 3 to 13 days as 20 separate courses of treatment, when high carbohydrate intake (300 g for a minimum of 72 hours) and supportive measures were unsuccessful. Urinary ALA and PBG levels were collected as well as clinical signs and symptoms of AIP recorded. Out of 20 treatment courses for acute attacks, there was a clinical response in 14. All patients had significant reductions in ALA and/or PBG levels after hemin treatment (p-value in the range from less than 0.001 to 0.05).

In another study by Lamon et al.5 seven patients with acute attacks of porphyria were administered 11 hemin courses (each course: 1 mg/kg every 24 hours for 3 to 13 days). Before and during hemin administration, patients were maintained on a 250-300 g/24H carbohydrate diet. Patients had elevated urinary ALA and PBG treatment and clinical evidence of an acute attack. Chemical response of a decrease in ALA and PBG occurred in every patient (except one PBG value in one patient) when treatment lasted 5 days or longer (p<0.001).

Figure 1: Efficacy Data on Hemin in Acute Intermittent   
Porphyria from 5 Open-Label Studies

Compassionate Use Study

In the compassionate use, multi-center, open-label, non-comparative study6, 130 patients were enrolled with a diagnosis of acute porphyria and were treated with hemin. The patients were administered hemin for acute attacks [N=90 (69%)], prophylaxis [N=19 (15%)], or both [N=21 (16%)]. There was a subset of patients in the "both" group (acute attacks and prophylaxis) who were treated for acute attacks prior to receiving prophylactic treatment. Seventy-two percent of the patients were female and 28% were male. Hemin was administered to 111 patients (enrolled in the "acute attack" and the "both" treatment groups) for the treatment of 305 acute attacks and to 40 patients (enrolled in the "prophylaxis" and the "both" treatment groups) for prophylactic treatment. Out of the 40 patients who received prophylaxis, 19 received prophylaxis only and 21 patients were treated for up to 3 acute attacks prior to receiving prophylactic treatment. Prophylaxis treatment varied greatly in frequency with the most common hemin regimen given once a week. Clinical response was achieved if the physician determined that the admitting symptoms were resolved, there was a clinically acceptable response, or the patient went into remission.

A physician-assessed clinical response was achieved for all acute attacks in 81 (73%) of 111 patients. Ninety-four patients (85%) of 111 had ≥1 clinical response and 17 patients (15%) of 111 had no response. Among 31 of 40 patients who received hemin prophylaxis for >1 month, 21 (68%) did not require subsequent hemin treatment for acute attacks.

Case Reports

In 234 courses, patients received hemin therapy as normally prescribed by their physicians with the majority dosed between the recommended range of 3 mg/kg/day to 4 mg/kg/day for at least one course of treatment. In these patients, hemin treatment was administered immediately in 33% of recipients, within 1 day of symptom onset in 50%, and within 3 days in 75%. These groups were not mutually exclusive. Most patients [108/111 (97.3%)] received a dose of at least 3 mg/kg/day and only 3 patients (2.7%) received a dose of hemin less than 2 mg/kg/day. There were 6 patients (5.4%) who were administered doses exceeding 6 mg/kg/day for 1 or more treatment courses.

Observational Patient Reported Outcomes Study

An observational study investigated patient reported outcomes in 108 patients with acute porphyrias.7 Out of 108 patients, 90 patients were with AIP and reported the following:

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     55% percent reported having received hemin during acute attacks, and 74% of these patients assessed PANHEMATIN therapy as very successful in the treatment of abdominal pain and other symptoms. 
•
     50% reported having received treatment with opiates during an acute attack, and 44% of these patients reported that opiates were effective. 

Hemin therapy effectiveness was assessed along with glucose infusions, high carbohydrate diets, and pain medications on a scale from zero being least effective to 10 highly effective. Hemin infusions received a 7.9, glucose infusions a 4.4 (p=0.0781), high carbohydrate diets a 4.7 (p=0.0021), and pain medications a 4.2 (p=0.0049).