Important Facts About H.P. Acthar® Gel
November 27, 2018
- Mallinckrodt is fully committed to H.P. Acthar® Gel (corticotropin respository injection). We believe strongly in the value it can provide to a variety of appropriate, often refractory patients suffering from difficult to treat diseases and conditions who often have few remaining options.
- Mallinckrodt has invested more than $400 million in the drug since 2014, and that investment includes seven ongoing company-sponsored, placebo-controlled clinical trials. The areas of focus for the trials include focal segmental glomerular sclerosis (a nephrotic condition), multiple sclerosis, pulmonary sarcoidosis, rheumatoid arthritis (RA), systemic lupus erythematosus, uveitis, and amyotrophic lateral sclerosis.
We are beginning to see the results of this work come to fruition, illustrated, in part, by interim data reported from our Phase 4 RA trial. This trial has completed enrollment of more than 250 patients, but the most recent data reported at the midpoint of the study showed 61% of patients with persistently active RA achieved low disease activity at 12 weeks . We look forward to reporting data from the completed trial in 2019, along with data from other H.P. Acthar Gel studies. This clinical data can provide insight to prescribers into the clinical utility of the drug across its approved indications, further guiding appropriate patient use.
- IIRs are not company-sponsored clinical trials. Like other companies that support investigator-initiated research (IIR), Mallinckrodt provides financial support to independent physicians who conduct other clinical studies into H.P. Acthar Gel. As the sponsor, we have no formal input into the design and conduct of the study, which is intended to be independent. We also have no input into publication of the study results. Those activities are the responsibility of the investigators, who routinely publish the data in clinical journals or present abstracts and posters at medical conferences.
In some cases, the sponsor may disagree with key trial design elements, as is the case with an IIR study in nephrotic syndrome publicly presented by the investigator at a medical conference in Toronto in May of this year. H.P. Acthar Gel is generally used in steroid-refractory, adult patients. That particular study targeted steroid-dependent, pediatric patients, which we believe likely impacted the results due to the rapid withdrawal of steroids in the dependent population.
- The goal of the proposed Acthar Hospital Starter Program for Infantile Spasms is to ensure that infants newly diagnosed with IS get the treatment they desperately need as quickly as possible. In the hospital systems across America where sick babies suffering from IS initially seek treatment – sometimes presenting with hundreds of seizures a day -- there is a delay of 3 to 5 days until they receive H.P. Acthar Gel, the U.S. Food and Drug Administration (FDA)-approved "gold standard" treatment for this condition.
To address this urgent newborn patient need for timely access to treatment, Mallinckrodt proposed the Acthar Starter Program for Infantile Spasms. Under the proposed program qualified healthcare professionals would have access to a vial of H.P. Acthar Gel in the hospital setting, at no cost to the hospital, the patient, or payer so as to avoid detrimental delays in treatment while reimbursement determination is pending. We designed the program similar to others used in the industry and proactively sought feedback from the OIG to ensure we would meet the appropriate guidelines. We're disappointed with the opinion rendered by the Office of Inspector General's Advisory Committee and are evaluating appropriate next steps.
IS is a rare condition affecting approximately 2,000 - 2,500 children in the U.S. each year, most of them under age 2. Sometimes called West Syndrome, IS demands immediate treatment to help limit lasting effects such as permanent development delays, physical limitations and intellectual impact. H.P. Acthar Gel is U.S. Food and Drug Administration-approved since 2010 as monotherapy for the treatment of IS in infants and children under 2 years of age. Mallinckrodt is committed to ensuring that any infant under the age of 2 suffering from IS who is prescribed the gold-standard therapy for IS to treat their disease receives treatment.
1 Full details on the interim data report and limitations can be found in the press release on http://mallinckrodt.com/about/news-and-media/
Visit www.mallinckrodt.com/acthar to learn more. About H.P. Acthar Gel (Repository Corticotropin Injection) Indications
H.P. Acthar Gel is an injectable drug approved by the FDA for the treatment of 19 indications. Of these, today the majority of Acthar use is in these indications:
- Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in RA, including juvenile RA (selected cases may require low-dose maintenance therapy)
- Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age
- Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
- The treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown H.P. Acthar Gel to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease
- Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus
- Treatment during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis)
- The treatment of symptomatic sarcoidosis
- Treatment of severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation
IMPORTANT SAFETY INFORMATION
- Acthar should never be administered intravenously
- Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar
- Acthar is contraindicated where congenital infections are suspected in infants
- Acthar is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction or sensitivity to proteins of porcine origins
Warnings and Precautions
- The adverse effects of Acthar are related primarily to its steroidogenic effects
- Acthar may increase susceptibility to new infection or reactivation of latent infections
- Suppression of the hypothalamic-pituitary-axis (HPA) may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. During recovery of the adrenal gland patients should be protected from the stress (e.g. trauma or surgery) by the use of corticosteroids. Monitor patients for effects of HPA suppression after stopping treatment
- Cushing's syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms
- Acthar can cause elevation of blood pressure, salt and water retention, and hypokalemia. Blood pressure, sodium and potassium levels may need to be monitored
- Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and for a period following discontinuation of therapy
- Acthar can cause GI bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain gastrointestinal disorders. Monitor for signs of bleeding
- Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression, and psychosis. Existing conditions may be aggravated
- Patients with comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar in patients with diabetes and myasthenia gravis
- Prolonged use of Acthar may produce cataracts, glaucoma and secondary ocular infections. Monitor for signs and symptoms
- Acthar is immunogenic and prolonged administration of Acthar may increase the risk of hypersensitivity reactions. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH activity
- There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver
- Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients
- Decrease in bone density may occur. Bone density should be monitored for patients on long-term therapy
- Pregnancy Class C: Acthar has been shown to have an embryocidal effect and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
- Common adverse reactions for Acthar are similar to those of corticosteroids and include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain
- Specific adverse reactions reported in IS clinical trials in infants and children under 2 years of age included: infection, hypertension, irritability, Cushingoid symptoms, constipation, diarrhea, vomiting, pyrexia, weight gain, increased appetite, decreased appetite, nasal congestion, acne, rash, and cardiac hypertrophy. Convulsions were also reported, but these may actually be occurring because some IS patients progress to other forms of seizures and IS sometimes mask other seizures, which become visible once the clinical spasms from IS resolve
Other adverse events reported are included in the full Prescribing Information.
Please see full Prescribing Information.
Mallinckrodt is a global business that develops, manufactures, markets and distributes specialty pharmaceutical products and therapies. Areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; analgesics and gastrointestinal products. To learn more about Mallinckrodt, visit www.mallinckrodt.com.
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CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS CONTACTS Investor Relations
This release includes forward-looking statements concerning H.P. Acthar Gel including expectations with regard to the study described in this release, as well as future research plans and potential impact on patients. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; and other risks identified and described in more detail in the "Risk Factors" section of Mallinckrodt's most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.
Daniel J. Speciale, CPA
Investor Relations and Strategy Officer
Senior Communications Manager
Chief Public Affairs Officer
Mallinckrodt, the "M" brandmark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. © 2018 11/18
Full details on the interim data report and limitations can be found in the press release on http://mallinckrodt.com/about/news-and-media/