FDA Updates: Merck’s Pneumococcal Vaccine Leads the Week

New vaccine for pneumococcal disease, an sNDA approved based on real-world data, a new therapy for skin and muscle disease, Keytruda combination receives full approval in endometrial cancer, a new diabetes therapy is approved, and another JAK inhibitor misses PDUFA date round out this week’s FDA news.

FDA approves Merck’s vaccine for pneumococcal disease. Merck announced the FDA has approved Vaxneuvance (Pneumococcal 15-valent Conjugate Vaccine), a vaccine to prevent pneumococcal disease in adults 18 years of age and older. The vaccine provides immunization for the prevention of invasive disease caused by several serotypes of Streptococcus pneumoniae.

The approval was based on data from seven randomized, double-blind clinical studies assessing safety, tolerability, and immunogenicity in adults. Clinical data showed that immune responses elicited by Vaxneuvance were non-inferior to the currently available 13-valent pneumococcal conjugate vaccine (PCV13) for the 13 shared serotypes.

Vaxneuvance is administered as a single dose via intramuscular injection. Common adverse reactions include pain at the injection site, fatigue, muscle pain, headache, redness and swelling at the injection site, and arthralgia.

“The FDA approval of Vaxneuvance builds on Merck’s more than 40 years of experience in pneumococcal disease prevention with a new option that includes serotypes responsible for substantial disease burden in adults, like serotype 3, as well as serotypes 22F and 33F, which are associated with a high degree of invasiveness and antibiotic resistance,” Roy Baynes, MB BCH, Ph.D., senior vice president and head of global clinical development, chief medical officer, at Merck Research Laboratories, said in a statement.

In January 2021, Vaxneuvance received Priority Review designation.

FDA approves Astellas’ Prograf for new use with real-world evidence. The FDA has approved Prograf (tacrolimus) for use in combination with other immunosuppressant drugs to prevent organ rejection in adult and pediatric patients receiving lung transplantation. This is the first approval of an immunosuppressant drug to prevent rejection in adults and pediatric patients who receive lung transplant.

This approval is based on a retrospective, observational study providing real-world evidence (RWE) of effectiveness. The data are from the U.S. Scientific Registry of Transplant Recipients, which captures data on all transplants performed in the United States. The study analyzed outcomes based on discharge immunosuppression treatment regimens in recipients of a primary lung transplant between 1999 and 2017.

In patients receiving Prograf in combination with azathioprine, the one-year graft survival estimates from time of discharge were 90.8% for adults and 84.7% for pediatric patients. Based on the SRTR study results, published clinical trials and postmarketing reports, the safety profile for lung transplant patients treated is consistent with the safety profile in liver, kidney and heart transplant patients treated with Prograf.

Prograf, originally approved to prevent organ rejection in patients receiving liver transplants, was later approved to prevent organ rejection for kidney and heart transplants.

Keytruda receives full approval in endometrial cancer. Merck has announced full FDA approval for the combination of Keytruda (pembrolizumab) in combination with Eisai’s Lenvima (lenvatinib) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy.

The approval is based on results from the pivotal phase 3 KEYNOTE-775/Study 309 trial, in which the combination of the two therapies demonstrated statistically significant improvements in overall survival, reducing the risk of death by 32%, and progression-free survival, reducing the risk of disease progression or death by 40%, versus chemotherapy.

The combination was previously approved under the FDA’s accelerated approval process, as well as under the agency’s Real-Time Oncology Review pilot program and its Project Orbis initiative, for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR.

FDA approves therapy for rare skin and muscle disease. The FDA has granted approval to Octapharma USA for Octagam 10% [Immune Globulin Intravenous (Human)], the first and only intravenous immunoglobulin (IVIg) to be indicated for the treatment of adult dermatomyositis, a rare immune-mediated inflammatory disease.

The approval is based on the results of ProDERM, a pivotal randomized clinical trial and the first study to evaluate the long-term efficacy and safety of intravenous immunoglobulin (IVIg) for adults with dermatomyositis.

During the initial 16-week phase, 78.7% of patients receiving Octagam responded positively to treatment as compared with 43.8% of those receiving placebo. After switching to IVIg in the extension period, the placebo group attained a similar response rate at week 40.

Dermatomyositis is a rare idiopathic autoimmune disorder of unknown cause affecting about 10 out of every million U.S. residents. Patients commonly suffer from skin rashes, chronic muscle inflammation and progressive muscle weakness, usually affecting adults between 40 and 60 years old. The estimated incidence of dermatomyositis is 9.63 cases per million people, according to the National Organization of Rare Disorders.

FDA approves therapy for severe itching for patients with liver disease. The FDA has approved Albireo Pharma’s Bylvay (odevixibat), the first treatment for pruritus in patients aged three months and older with progressive familial intrahepatic cholestasis (PFIC), a rare progressive liver disease that typically leads to liver failure. In many cases, PFIC leads to cirrhosis and liver failure within the first 10 years of life.

Bylvay is a potent, non-systemic ileal bile acid transport inhibitor (IBATi), which does not require refrigeration and is easily administered as a once-daily capsule or sprinkled on food. The approval of was supported by from two global, phase 3 trials.

In the first trial, PEDFIC 1, Bylvay met both its pruritus and serum bile acid primary endpoints and was well tolerated with very low incidence of diarrhea/frequent bowel movements. The second trial, PEDFIC 2, reaffirmed Bylvay delivered sustained reductions in serum bile acids as well as improvements in pruritus assessments, growth and other markers of liver function in patients treated up to 48 weeks.

FDA approves AstraZeneca’s pediatric diabetes therapy Bydureon BCise. The FDA has approved AstraZeneca’s Bydureon BCise (exenatide extended-release), a once-weekly injectable suspension for the treatment of type 2 diabetes and to improve glycemic control in pediatric patients.

The approval was based on the results of a phase 3 trial in children between 10 and 17 years old. In this trial, patients were treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin were randomized to receive Bydureon BCise or placebo. Investigators found that patients who received Bydureon BCise achieved a significantly greater mean change in HbA1c from baseline compared with placebo.

Bydureon BCise was approved in the United States in October 2017 as a once-weekly single-dose autoinjector device for adults with type 2 diabetes. It was also approved for use in the EU in August 2018.

FDA to miss PDUFA date for sNDA for Xeljanz. Pfizer has announced the FDA will not meet the PDUFA goal date for a decision on the supplemental NDA for Xeljanz (tofacitinib) for the treatment of adults with active ankylosing spondylitis. The FDA had previously extended the PDUFA goal dates to early third quarter 2021. ​The FDA cited its ongoing review of Pfizer's post-marketing safety study, ORAL Surveillance, evaluating tofacitinib in rheumatoid arthritis patients, as a factor for the extensions.

XELJANZ is approved in the United States for four indications: adults with moderately to severely active rheumatoid arthritis (RA) after methotrexate failure, adults with active psoriatic arthritis, adults with moderately to severely active ulcerative colitis after tumor necrosis factor inhibitor failure, and patients 2 years of age or older with active polyarticular course juvenile idiopathic arthritis

In January, Pfizer released results from its post-marketing cardiovascular safety trial of Xeljanz in patients with rheumatoid arthritis. This study compared Xeljanz with a TNF inhibitor and included 4,362 subjects who received study treatments.

The primary analyses included 135 subjects with major adverse cardiovascular events (MACE) and 164 subjects with malignancies (excluding non-melanoma skin cancer). For tofacitinib, the most frequently reported MACE was myocardial infarction and the most frequently reported malignancy (excluding NMSC) was lung cancer. In those subjects with a higher prevalence of known risk factors for MACE and malignancy (e.g., older age, smoking), a higher occurrence of events was seen across all treatment groups.