Merck Vaccine and Other FDA Updates

Keytruda gets a full approval in endometrial cancer; while Xeljanz will miss another PDUFDA date.

Pneumococcal vaccine approved. Merck announced late July 16 that the FDA had approved Vaxneuvance (Pneumococcal 15-valent Conjugate Vaccine), a vaccine that provides protection against invasive disease caused by several serotypes of Streptococcus pneumoniae. It is approved for adults 18 years of age and older, based on data from seven randomized clinical trials that showed immune responses elicited by Vaxneuvance were non-inferior to the currently available 13-valent pneumococcal conjugate vaccine (PCV13) for the 13 shared serotypes. Merck’s new vaccine 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.

Full approval for Keytruda in endometrial cancer. Merck on Thursday 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. Approval is based on results from the pivotal phase 3 KEYNOTE-775/Study 309 trial, which showed the combination significantly improved 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. Previously, the combination received accelerated approval.

Real-world evidence used in Prograf approval in lung transplants. On Tuesday, the FDA approved Astellas’ Prograf (tacrolimus), the first approval of an immunosuppressant drug to prevent organ rejection in adults and peditatric patients who receive lung transplant. Approval is based on an observational study using 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 who received 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. The safety profile for lung transplant patients treated was consistent with the safety profile in liver, kidney and heart transplant patients treated with Prograf.

Approval for AstraZeneca’s pediatric diabetes therapy Bydureon BCise. The FDA on Friday 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 action was based on findings from a 24-week phase 3 trial with a 28-week open-label extension involving patients aged 10 to 17 years, which found those taking the study drug alongside a regimen of diet and exercise alone or diet, exercise and oral agents and/or insulin achieved a greater average reduction in A1C compared with placebo. Previously, Bydureon BCise was approved in the United States as a once-weekly single-dose autoinjector device for adults with type 2 diabetes.

Another missed PDUFA date for Xeljanz. Pfizer announced Wednesday that the FDA will not meet the goal date for a decision under the Prescription Drug User Fee Act (PDUFA) 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.

First therapy for rare skin and muscle disease. On Tuesday, the FDA granted approval to Octapharma USA for Octagam 10% [Immune Globulin Intravenous (Human)], the first intravenous immunoglobulin (IVIg) to be indicated for the treatment of adult dermatomyositis, a rare immune-mediated inflammatory disease. 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. In the initial 16-week phase, 78.7% of patients receiving Octagam responded positively to treatment, compared with 43.8% 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 that affects adults between age 40 and 60 years old, who suffer from skin rashes, chronic muscle inflammation and progressive muscle weakness. 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. Also on Tuesday, the FDA approved Albireo Pharma’s Bylvay (odevixibat), for treatment of pruritus, which causes a severe urge to scratch in patients aged three months and older who have 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.