Cambridge, Mass. – January 4, 2018 – Shire plc (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for maribavir (SHP620), a Phase 3 investigational treatment for cytomegalovirus (CMV) infection and disease in transplant patients resistant or refractory to prior therapy. By targeting a key CMV enzyme, maribavir is thought to inhibit CMV DNA replication and encapsidation, and prevent the escape of viral capsids from the nucleids of infected cells.
CMV is a beta herpes virus that, in patients with compromised immunity including organ or stem cell transplant recipients, causes clinically challenging complications that can be fatal. Existing antiviral therapies can be used to treat CMV, but their use may be limited by side effects and/or drug resistance.
“Maribavir has the potential to address critical medical needs for transplant patients who are refractory or resistant to currently available antiviral therapies, and I’m proud of the innovation and hard work that made this Breakthrough Designation Therapy milestone a reality,” said Andreas Busch, Global Head of R&D, Shire. “We are delighted that the FDA has granted Breakthrough Therapy Designation to maribavir and we continue to work every day to deliver therapies to the patients who need them most. We are eager to work with the FDA to continue development of maribavir.”
According to the FDA, Breakthrough Therapy Designation is granted to a therapy that is intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over available or existing therapy. Under the designation, the FDA provides intensive guidance on an efficient drug development program, organizational commitment involving senior managers, and eligibility, based on supporting clinical data, for rolling and priority review of the marketing application; this process helps ensure patients have access to therapies as soon as possible, pending approval. Breakthrough Therapy Designation does not guarantee that FDA will approve maribavir for the treatment of CMV infections in transplant patients, and the timing of any such approval is uncertain.
Breakthrough Therapy Designation status for maribavir was granted based on the data from two Phase 2 studies, including a Phase 2 trial in 120 patients ages 12 or older with CMV infection. In the study, 67% of patients treated with varying doses of maribavir (400 to 1200 mg twice daily) for up to 24 weeks had no detectable levels of the virus in their blood plasma within six weeks of starting treatment. Dysgeusia (taste disturbance) was the most commonly reported treatment-emergent adverse event (AE) considered to be related to maribavir. Other related treatment-emergent AEs occurring in greater than or equal to 5% of study participants for any dose included nausea, CMV infection, immunosuppressant drug level increased, diarrhea, rash, vomiting, anaemia, and pruritus (itch).
Maribavir, an investigational agent that is in a class of drugs called benzimidazole ribosides, is an orally bioavailable antiviral therapy being evaluated in patients with CMV infection after undergoing hematopoietic stem cell transplant or solid organ transplant. By inhibiting the CMV UL97 protein kinase, maribavir potentially affects several critical processes in CMV replication including viral DNA synthesis, viral gene expression, encapsidation and egress of mature capsids from the nucleus. Further research to confirm these findings will be conducted in pending Phase 3 studies.
The U.S. Food and Drug Administration (FDA) and the European Commission have granted Orphan Drug Designation to maribavir for treatment of clinically significant CMV viremia and disease in at-risk patients, and treatment of CMV disease in patients with impaired cell mediated immunity, respectively.
CMV is a common virus that infects people of all ages. In the U.S., by age 40, over half of adults have been infected with CMV, most showing no signs or symptoms. However, in people with compromised immunity, CMV infection is a serious clinical complication that can lead to tissue-invasive disease and ultimately be fatal.
Shire is the leading global biotechnology company focused on serving people with rare diseases. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.
Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest.
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- Shire’s products may not be a commercial success;
- increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire’s future revenues, financial condition and results of operations;
- Shire conducts its own manufacturing operations for certain of its products and is reliant on third party contract manufacturers to manufacture other products and to provide goods and services. Some of Shire’s products or ingredients are only available from a single approved source for manufacture. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;
- the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
- certain of Shire’s therapies involve lengthy and complex processes, which may prevent Shire from timely responding to market forces and effectively managing its production capacity;
- Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
- the actions of certain customers could affect Shire’s ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial conditions or results of operations;
- Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;
- adverse outcomes in legal matters, tax audits and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on the Company’s revenues, financial condition or results of operations;
- inability to successfully compete for highly qualified personnel from other companies and organizations;
- failure to achieve the strategic objectives, including expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all with respect to Shire’s acquisitions, including NPS Pharmaceuticals Inc., Dyax Corp. or Baxalta Incorporated may adversely affect Shire’s financial condition and results of operations;
- Shire’s growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products;
- a slowdown of global economic growth, or economic instability of countries in which Shire does business, as well as changes in foreign currency exchange rates and interest rates, that adversely impact the availability and cost of credit and customer purchasing and payment patterns, including the collectability of customer accounts receivable;
- failure of a marketed product to work effectively or if such a product is the cause of adverse side effects could result in damage to Shire’s reputation, the withdrawal of the product and legal action against Shire;
- investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire’s activities in the highly regulated markets in which it operates may result in significant legal costs and the payment of substantial compensation or fines;
- Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire’s revenues, financial condition or results of operations;
- Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which may decrease its business flexibility and increase borrowing costs; and
a further list and description of risks, uncertainties and other matters can be found in Shire’s most recent Annual Report on Form 10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in “ITEM 1A: Risk Factors”, and in Shire’s subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire’s website.
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