27 July 2018
`EMA/CHMP/510214/2018
`Media and Public Relations
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`Press release
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`New medicine for hereditary rare disease
`Onpattro addresses unmet medical need for treatment of hereditary
`transthyretin amyloidosis
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`The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has
`recommended granting a marketing authorisation for Onpattro (patisiran), for the treatment of
`hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or
`stage 2 polyneuropathy (a condition in which the peripheral nerves are damaged). This medicine is
`expected to affect the course of the disease and improve patient functioning and quality of life.
`
`hATTR amyloidosis is an inherited, rare, life-threatening disease. It is caused by mutations in the
`transthyretin (TTR) gene that result in misfolded TTR proteins accumulating as amyloid fibrils in
`multiple sites, including the nerves, heart and gastrointestinal tract. Patients with this condition usually
`have heart problems and symptoms such as muscle weakness in the limbs and, at later stages,
`inability to walk, problems affecting the stomach and the gut (leading to malnutrition), and bladder
`dysfunction. hATTR amyloidosis is more frequent in men than women.
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`Onpattro contains patisiran, a medicine made of a small strand of synthetic genetic material called
`‘small interfering RNA’ (siRNA) designed to attach to the genetic material of the cells responsible for
`producing the TTR protein and block its production in the liver. This decreases TTR production, thereby
`reducing the accumulation of TTR amyloid in the tissues and slowing down the progression of the
`disease. Onpattro is administered via intravenous infusion once every three weeks.
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`The safety and efficacy of Onpattro was evaluated in a pivotal trial involving 225 patients with hATTR
`amyloidosis and symptomatic polyneuropathy. The study showed clinically-relevant improvements in
`the neurological manifestations of the disease and on patients’ quality of life, as well as a positive
`impact on cardiac parameters. The efficacy of this treatment in patients with stage 3 polyneuropathy
`has not yet been demonstrated. The most common adverse events observed were infusion-related
`reactions like flushing, back pain, nausea, abdominal pain, dyspnoea (shortness of breath) and
`headache.
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`Onpattro is the second medicine recommended for authorisation in this disease, following the positive
`opinion for Tegsedi (inotersen) in May 2018. These two medicines considerably widen the therapeutic
`options for this disease, which currently include liver transplant, treatment with tafamidis and off-label
`use of non-steroidal anti-inflammatory drugs (NSAIDs). All of them have considerable limitations for
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`PROTIVA - EXHIBIT 2025
`Moderna Therapeutics, Inc. v. Protiva Biotherapeautics, Inc. - IPR2018-00739
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`patients with stage 2 and stage 3 polyneuropathy, meaning there is a clear unmet medical need.
`Therefore, the CHMP considered that Onpattro was of major interest for public health and agreed to
`the applicant’s request for an accelerated assessment of this medicine.
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`Onpattro was designated as an orphan medicine in April 2011. As always at time of approval, EMA’s
`Committee for Orphan Medicinal Products (COMP) will review the orphan designation to determine
`whether the information available to date allows maintaining Onpattro’s orphan status and granting
`this medicine ten years of market exclusivity.
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`The opinion adopted by the CHMP is an intermediary step on Onpattro’s path to patient access. The
`CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-
`wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price
`and reimbursement will take place at the level of each Member State, taking into account the potential
`role/use of this medicine in the context of the national health system of that country.
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`Notes
`1. This press release, together with all related documents, is available on the Agency's website.
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`2. The applicant for Onpattro is Alnylam Netherlands B.V.
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`3. More information on the work of the European Medicines Agency can be found on its website:
`www.ema.europa.eu
`
`Contact our press officers
`Tel. +44 (0)20 3660 8427
`E-mail: press@ema.europa.eu
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`New medicine for hereditary rare disease
`EMA/CHMP/510214/2018
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