Summary of the safety profile: Data from two phase 3 and two phase 2 clinical studies in migraine were pooled to evaluate the safety of Pasurta in comparison to placebo up to 12 weeks after treatment initiation.
There were a total of 2656 patients (1613 Pasurta and 1043 placebo) in these studies. Of these, 893 subjects received 70 mg dose of Pasurta and 507 subjects received 140 mg dose of Pasurta.
The overall safety population including ongoing open label extension phases with Pasurta includes 2537 patients (2310.3 patient years) who received at least one dose of Pasurta: 2066 patients were exposed for at least 6 months and 1213 patients were exposed for at least 12 months.
Tabulated summary of adverse drug reactions: Table 7 summarizes all adverse reactions that occurred in Pasurta-treated patients during the 12-week placebo-controlled period of the pooled trials. Most of the Adverse Drug Reactions (ADR's) were mild or moderate in severity.
Frequency is provided by CIOMS category (e.g., Very Common (≥ 10%), Common (≥ 1% and < 10%), uncommon (≥ 0.1% and < 1%), rare (≥ 0.01% and < 0.1%), very rare (< 0.01%)). (See Table 7.)
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Description of selected adverse reactions: Injection site reactions: In the integrated 12-week placebo-controlled period of studies, in subjects treated with Pasurta the most frequent injection site reactions were injection site pain, injection site erythema, and injection site pruritus. A majority of injection site reactions were Grade 1 in severity (mild) and transient. Injection site pain typically subsided within 1 hour after administration. One subject treated with Pasurta 70 mg SC discontinued due to injection site rash and no subject treated with Pasurta 140 mg SC discontinued due to injection site reactions in the 12-week placebo-controlled period of studies.
Constipation: In the integrated 12-week placebo-controlled period of studies, 28 cases of constipation were reported out of 1400 Pasurta-treated patients. All were mild or moderate severity. A majority of the cases (23) had onset within one month after the first dose; however, some patients also presented with constipation later on in treatment. In most cases (18), constipation resolved within three months. All but one case continued treatment.
Post-Marketing Experience: Immune system disorders: Hypersensitivity reactions including rash, angioedema and anaphylactoid reactions [see PRECAUTIONS].
Gastrointestinal disorders: Constipation with serious complications [see PRECAUTIONS].
Oral sores (e.g., stomatitis, mouth ulceration, oral mucosal blistering).
Skin and subcutaneous tissue disorders: Alopecia, Rash (e.g., rash papular, exfoliative rash, rash erythematous, urticaria, blister).
Immunogenicity: As with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity of Pasurta has been evaluated using an immunoassay for the detection of binding anti-erenumab antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies.
In the four migraine prophylaxis efficacy studies [20120178, 20120295, 20120296 and 20120297], the incidence of anti-erenumab antibody development during the double-blind treatment phase was 6.3% (56/884) among subjects receiving the 70 mg dose of Pasurta (three of whom had in-vitro neutralizing activity) and 2.6% (13/504) among subjects receiving 140 mg dose of Pasurta (none of whom had in-vitro neutralizing activity). There was no impact of anti-erenumab antibody development on efficacy or safety of erenumab.
The incidence of anti-drug antibodies (ADAs) is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to erenumab with the incidence of antibodies to other products may be misleading.