FDA Bestows Breakthrough Tag on Shire's Maribavir

Shire (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).

About Maribavir

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.

About CMV

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.

About Shire

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.