MNK Response to CNN

6.22.18

Any of the following sections may be attributed to Mallinckrodt or "a spokesperson for the
company."
Summary response:
H.P. Acthar Gel makes a significant difference in the lives of very sick patients with
unmet medical needs. We are proud of the drug and the important investment we are
making in it. Currently approved in the U.S. for 19 indications, HP. Acthar Gel is largely
used as a later line treatment, prescribed by skilled healthcare providers to a small
subset of appropriate patients who need an alternative treatment option. For infantile
spasms patients, H.P. Acthar Gel is FDA-approved as a monotherapy treatment.
Mallinckrodt has invested substantially in H.P. Acthar Gel since acquiring it in 2014,
generating further data supporting its use, and has made only modest price adjustments.
The company has acted and continues to act responsibly and ethically in its dealings
with healthcare practitioners and others.
Physician Payments/Travel Expense Reimbursement:
In the period of 2013-2016, of all healthcare practitioners prescribing H.P. Acthar Gel to whom
Mallinckrodt or the prior owner made payments, more than 95% received only modest meals
or nominally priced clinical reprints - well within regulations and guidelines. For the
remaining ~5%, the vast majority were engaged for peer-to-peer speaking engagements, with a
small fraction involved in other consulting services for the company, such as speaking to
employees or investors and participation in expert Physician Advisory Boards - again, all within
regulations and guidelines. It is our belief that many physicians prefer peer-to-peer
presentations and dialogue over other methods of learning about the value a product may bring
to appropriate patients they are treating. The physicians who present to their peers must take
time away from their practice and frequently travel to other cities - incurring normal, but
sometimes substantial travel expenses. Any payments reported include reimbursement for
these expenses.
Mallinckrodt designs our policies to be consistent with applicable legal and regulatory
requirements, the PhRMA Code, and industry best practices. We have instituted controls and
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MNK Response to CNN

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strict guidelines regarding the selection and training of speakers; the conduct of such programs,
including requirements related to the individuals that may attend such programs; and guidelines
to ensure that the venues selected for such programs are appropriate and conducive to the
educational focus of these programs, and payments are based on fair market value.
H.P. Acthar Gel is FDA-Approved for 19 Indications:
While H.P. Acthar Gel has been used to treat patients for more than 50 years, the U.S. Food
and Drug Administration (FDA) reviewed its label most recently in 2010, at which time the FDA
determined there was existing, sufficient scientific and clinical evidence to support its use in the
19 various indications contained in the current H.P. Acthar Gel label.
One of these indications is for use of H.P. Acthar Gel in the treatment of Infantile Spasms
(IS),1 for which it is considered the gold standard for treatment. Two randomized clinical trials
were submitted in support of FDA approval of the drug and its effectiveness as a treatment for
IS, one of which compared H.P. Acthar Gel to prednisone. In that trial 86.7% of patients had a
positive response to H.P. Acthar Gel vs. 28.6% that responded to prednisone. Patients who
responded in the pivotal study treated with a two-week course of H.P. Acthar Gel therapy
experienced complete suppression of the two key measures of disease – spasms and
hypsarrhythmia. The IS clinical trial results appear in Section 14 of the full prescribing
information for the drug.
Aside from treatment of IS, H.P. Acthar Gel is often prescribed by doctors predominantly as a
later-line treatment to a small subset of patients suffering from various devastating diseases for
whom other approved FDA treatment options have failed.
Significant Clinical Evidence Supports the Efficacy of H.P. Acthar Gel:
There is significant clinical evidence to support the effectiveness of H.P. Acthar Gel. This
evidence is the result of company-sponsored controlled clinical trials, investigator-initiated
research conducted in top hospitals and medical centers by some of the country's preeminent
physicians, and health economic and outcomes research data. Equally important, there are
decades of clinical experience that doctors have with the product as a proven therapy for
appropriate patients.
The JAMA letter you referenced is merely “a letter” to the editor submitted by a physician who,
for years, has been critical of the drug. H.P. Acthar Gel is an FDA-approved therapy for acute
exacerbations of MS (or MS relapses) in adults. Steroids are commonly used as a first line
treatment of MS relapse; however, North American Research Committee on Multiple Sclerosis
(NARCOMS) data indicates 30% of MS relapse patients had no response to steroids.2

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Because symptoms of IS can be subtle and are generally not widely recognized, Mallinckrodt invests resources to
support education of the medical and patient community to ensure IS babies are getting diagnosed promptly. We also
invest in ongoing clinical research to further understand the disease and since treating infantile spasms is so urgent
once diagnosed Mallinckrodt has established an entire support team to usher each baby’s prescription through the
coverage process to ensure quick access to the product.
2

Nickerson, M., et al., Impact of multiple sclerosis relapse: The NARCOMS participant perspective. Multiple sclerosis
and related disorders, 2015. 4(3): p. 234-240.

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Additionally, some patients cannot tolerate steroids. Nearly 20% of patients consider avoiding
relapse therapy due to steroid adverse events (AEs).3
Both the American Academy of Neurology and the National Multiple Sclerosis Society have said
that alternative treatment options are needed for patients with MS relapse who cannot tolerate
steroids, do not respond to steroids or do not want to take steroids.4 5 Accordingly, H.P. Acthar
Gel may provide an option for patients who need an alternative treatment option.
Mallinckrodt has a company-sponsored clinical trial underway to further assess the efficacy and
safety of H.P. Acthar Gel in patients with MS relapse, and is conducting an observational
registry to evaluate the use of the drug for treatment of MS relapse. You can access a recent
interim report on those findings here. Similarly, as part of the company’s significant investment
into H.P. Acthar Gel, a number of other clinical studies are ongoing, including one in rheumatoid
arthritis patients. We recently provided an interim report on those findings as well which can be
found here.
The Price of H.P. Acthar Gel:
In 2007, H.P. Acthar Gel’s previous owner was near bankruptcy and raised the price of the drug
substantially in order to keep the drug on the market and to ensure the long-term supply of the
drug for treatment of children afflicted with infantile spasms and other small groups of patients
suffering from complex, devastating diseases. They did this only after extensive consultation
with the FDA.6
Today the price per vial of H.P. Acthar Gel is $38,892. Since acquiring H.P. Acthar Gel,
Mallinckrodt has only made modest price adjustments in the mid-single digit percentage range.
Additionally, Mallinckrodt provides discounts to this list price to payers, which the prior owner
generally did not offer. We would encourage you to review Mallinckrodt's pledge on drug pricing
and innovation, which we take very seriously.
Mallinckrodt’s Investment in H.P. Acthar Gel:
In contrast to the drug’s prior owner, since acquiring H.P. Acthar Gel in 2014 Mallinckrodt has
invested nearly $400 million into the drug. Specifically: building on substantial clinical
experience as well as previously completed and largely independent clinical case series and
smaller trials; modernizing manufacturing; expanding medical affairs and research activities;
3

Jongen, P.J., et al., Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment: a
prospective web-based multi-center study in multiple sclerosis patients with a relapse. Journal of Neurology, 2016: p.
1-11.
4

Society, N.M.S. Managing Relapses Understand the definition and cause of MS relapses (exacerbations) and learn
about medications and rehabilitation strategies to manage them.; Available from:
http://www.nationalmssociety.org/Treating-MS/Managing-Relapses.
5

Cortese, I., et al., Evidence-based guideline update: Plasmapheresis in neurologic disorders Report of the
Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology, 2011.
76(3): p. 294-300.
Please see the Questcor’s 10-K filing for 2007. Additionally, Questcor issued many new shares the year before,
presumably to raise capital. Moreover, articles have appeared, including one in Investor’s Business Daily in
November of 2013 in which the former CEO of Questcor publicly discussed the company’s challenges to stay afloat
during this time period.
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and initiating six well-designed, company-sponsored randomized, controlled clinical studies,
targeting combined enrollment of nearly 1,100 patients.7
Adverse Events:
As an FDA-approved drug, H.P. Acthar Gel is deemed safe and effective for its labeled
indications by the agency.
Mallinckrodt annually provides the FDA with data about adverse events related to its marketed
products. As we approach our yearly filing, we are pleased to report that the positive benefit-risk
of H.P. Acthar Gel has remained unchanged across all marketed indications and is consistent
with previous years. To derive meaningful conclusions of this topic, adverse event reports for
H.P. Acthar Gel need to be considered within the appropriate context.
H.P. Acthar Gel is typically prescribed to patients with very serious medical conditions, often as
a third or fourth line of treatment when other treatments have failed. It is well known that many
of these patients suffer from diseases in which co-morbidities are high, and often they are on
other medications that may be contributing factors. The frequency of adverse event reports also
does not necessarily correlate to an increase in the actual prevalence or relative severity of any
particular side effect or event. Each event is reported and counted whether it relates to a
relatively minor event such as a headache or a more serious event such as anaphylaxis.
Furthermore, the FDA itself cautions on its website that reporting of a side effect or adverse
event occurring while taking a drug doesn’t establish a causal relationship between the adverse
event and the medicine.
Over the past years, the number of patients using H.P. Acthar Gel has increased significantly.
Critically, however, company-generated H.P. Acthar Gel data on adverse events over the last
four calendar years indicates that the number of serious adverse events as a proportion of the
number of H.P. Acthar Gel prescriptions (measured by vials sold) has remained very low and
consistent with the FDA’s independent analysis.
H.P. Acthar Gel Advisory Committee Results
Regarding your questions on this topic, these are the facts: On May 11, 2010, a meeting of the
FDA’s Peripheral and Central Nervous System Drugs Division held an Advisory Committee
Meeting (AdCom) to review/discuss the data Questcor was submitting/had submitted in support
of use of H.P. Acthar Gel in treatment of patients with Infantile Spasms. The Committee voted
22 to 1 that H.P. Acthar Gel was an effective treatment for patients with IS and voted 20 to 1 the
drug was safe in the intended patient population at an effective dosing regimen, inclusive of a
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The six ongoing clinical trials are referenced below. Each link takes you to the announcement of the first patient
enrolled in the clinical trial. Within each press release, in the “About the Trial” section, you will see a link to further
details about the study that can be found on www.clinicaltrials.gov. These important investments will build upon the
existing body of clinical evidence to support the effectiveness of H.P. Acthar Gel.
• Phase 2B trial in Amyotrophic Lateral Sclerosis
• Phase 4 trial in Pulmonary Sarcoidosis
• Phase 4 trial in Multiple Sclerosis Relapse
• Phase 4 trial in Lupus
• Phase 4 trial in Rheumatoid Arthritis
• Phase 4 trial in Focal Segmental Glomerulosclerosis (Nephrotic Syndrome)
Studies conducted prior to Mallinckrodt’s acquisition of Acthar, as well as more recently completed research activities,
are listed in the bibliography section of Mallinckrodt’s website.

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Risk Evaluation and Mitigation Strategy (REMS). The REMS was a part of the agency’s
eventual approval of the drug for this indication (along with the reaffirmation of 18 others) in
2010. Two years later, the FDA removed the REMS requirement based on H.P. Acthar Gel’s
demonstrated safety in the market in IS patients.
Synacthen, H.P. Acthar Gel and the FTC Settlement:
Synacthen® (tetracosactide) is not a generic competitor to H.P. Acthar Gel. The two products
are very different drugs. While the two drugs may share mechanistic effects through the ACTH
component, H.P. Acthar Gel is much more. H.P. Acthar Gel is a naturally sourced complex
mixture of purified adrenocorticotropic hormone analogs and other pituitary peptides – not a
steroid – and amongst its many components includes a 1-39 peptide chain, meaning it includes
more than simply ACTH. Synacthen is a synthetic ACTH 24-peptide chain.
The company believes the regulatory path for any corticotropin-type new drug application
requiring clinical trials and FDA approval and could take many years if successful. Mallinckrodt
did not pursue commercialization of Synacthen for IS, as the barriers to completion were, in our
view, virtually impossible to overcome.
Notably, Synacthen has never been approved by the FDA for use in the U.S. for any indication
and it is not an alternative treatment for IS in the U.S. In all the time that Synacthen has been
commercially available in select foreign countries, it has never been commercialized in the U.S.
and no owner of Synacthen (including the owner prior to Questcor) ever undertook U.S.
development of the drug in IS or any other indication.
Even in Canada, where Synacthen is approved and used in certain indications, it is not
approved for use in IS patients. In Canada, the label contains a warning against use in infants or
children under 3 years old due to the product containing benzyl alcohol.
Once Mallinckrodt acquired the prior owner of Synacthen, we began developing the drug and in
2016, prior to the U.S. Federal Trade Commission (FTC) settlement. Mallinckrodt is developing
the drug (MNK-1411) in an indication where there is both high unmet medical need and, if
successful, potential for greatest impact for patients – Duchenne Muscular Dystrophy.
The Rockford Lawsuit:
Mallinckrodt strongly believes that none of the company actions outlined in the plaintiff’s
complaint constitute a violation of any law and, therefore, believes that the complaint should be
dismissed in its entirety. We will vigorously defend the company in this matter.
Treating physicians prescribe what they believe is best for their patients and the doctor(s) in
Rockford, Illinois chose to prescribe H.P. Acthar Gel.
Whistleblower Matter:
When Ms. Dhaliwal made the allegations outlined in her lawsuit known to Mallinckrodt, the
company promptly engaged the services of an outside legal counsel, who conducted a thorough
review of her concerns. We believe the company has acted responsibly at all times, strongly
disagree with these allegations and intend to vigorously defend this matter.
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