First Microbiome Product Approved

Rebyota^™ (fecal microbiota, live-jslm – Ferring Pharmaceuticals) suspension received approval from the U.S. Food and Drug Administration (FDA) on Nov. 30, 2022. The first FDA-approved biotherapeutic (a treatment that contains living organisms), it is a fecal transplant indicated as a single dose given rectally one to three days following a course of antibiotics used to treat a Clostridioides difficile infection (CDI) that occurs after the patient already has had at least one prior CDI. Responsible for as many as 500,000 infections and 30,000 deaths in the U.S. each year, CDIs cause diarrhea, fever, nausea, and other symptoms, which can include inflammation of the colon. Typically, they are treated with antibiotics, which frequently result in another infection with CD due to disruptions in the microorganisms that inhabit the intestinal tract (the gut microbiome). Up to 65% of patients – particularly institutionalized patients, seniors, and those who have immune deficiencies – have repeated CD infections. By restoring a more normal balance of microorganisms in the gut, Rebyota prevents recurring CDIs for adults who have had them. Clinical trials of its use included about one thousand patients. In the most recent one, Rebyota prevented a new CD infection for at least eight weeks for 70.6% of patients who received it, as compared to 57.5% of patients who got a placebo treatment. Among the responders to active treatment, over 90% were still CDI-free six months after therapy. Rebyota is derived from human feces that are donated by individuals who have been screened to rule out infectious diseases. Although very slight, it does still have the potential for transmitting a disease or a food allergy. A specialty product, it is shipped and maintained at extremely cold temperatures before being thawed and administered. Rebyota will be dispensed in kits that contain one dose (150mL) plus an administration set. The FDA awarded it Breakthrough Therapy, Fast Track, and Orphan Drug designations. Distribution will begin in mid-December through a small network of specialty pharmacies that includes Accredo. The cost has not yet been announced. Another company, Seres Therapeutics, is developing an SER-109, an oral product that contains a live microbiome derived from spores of a normal gut bacterium, Firmicutes, that also come from fecal material donated by individuals who have been vetted. It is taken in four capsules once each day for three days in a row. Clinical study results of its use have been similar to those of Rebyota. SER-109 is under the FDA’s Priority Review with an action date of April 26, 2023.

Rezlidhia Approved

On Dec. 1, 2022, the FDA approved Rezlidhia™ (olutasidenib) capsules for the treatment of adults who have acute myeloid leukemia (AML) that has returned or become unresponsive to previous therapy (r/rAML). Patients also must test positive for mutations in isocitrate dehydrogenase-1 (IDH1) enzymes. According to the American Cancer Society (ACS), approximately 21,000 patients – mostly adults over 45 years of age – are diagnosed with AML in the United States each year. Relapses or resistance to treatment eventually affect as many as one-half of patients. Between 6% and 16% have IDH1 mutations. Normally, IDH1 helps to break down fats from food, regulate glucose levels and protect against oxidative stress. Mutated IDH1 converts normal substances into 2-hydroxyglutarate (2-HG), which promotes cancer cell formation. By blocking the production of 2-HG, Rezlidhia lessens the creation of AML cells. In its decisive clinical trial, 35% of patients taking it achieved a complete response with at least some recovery of peripheral blood counts (CR+CRh). On average, CR lasted for 28.1 months. It is taken as one 150mg capsule twice a day, one hour or more before or two hours or more after eating. Its labeling has a boxed warning because about 16% of patients using Rezlidhia in clinical trials developed differentiation syndrome, a potentially fatal condition caused by the very fast production of immature myeloid cells in the bone marrow. Additionally, around one-fourth of patients in studies had some degree of liver damage that mainly was corrected with changes in dosage. Rigel Pharmaceuticals has not released the cost or launch plans for Rezlidhia. The first IDH1 inhibitor, Tibsovo^® (ivosidenib – Sevier Pharmaceuticals) tablets, initially was FDA-approved in July 2018 for treating adults who have r/rAML confirmed as having IDH1 mutations. Later, it also was approved alone to treat IDH1-mutated cholangiocarcinoma (cancer in the bile ducts) and along with azacitidine injection as initial treatment for new cases of IDH1-positive AML in patients who are at least 75 years old or who have coexisting medical conditions that preclude induction doses of chemotherapy (chemo).

New Brexafemme Indication

The FDA approved a new indication for Brexafemme^® (ibrexafungerp – Scynexis) tablets on Nov 30, 2022. Originally approved in June 2021, it is indicated to treat vulvovaginal candidiasis (VVC), which often is called yeast infections. Now, it also can be used to decrease the number of recurring vulvovaginal candidiasis (RVVC) episodes. A triterpenoid antifungal drug, it destroys yeast cells by blocking an enzyme needed for building strong cell walls. Recommended dosing is two 150mg tablets in the morning and two more about 12 hours later, for a total of 600mg in one day. To treat VVC, treatment lasts only one day; for RVVC the four-tablet regimen is repeated once a month for a total of six months. Brexafemme has a boxed warning that it should not be prescribed for women who are pregnant because it may damage a developing fetus. Women of childbearing age should consistently use a reliable contraceptive during treatment and for at least four days after the last dose. Girls who have not yet started having periods also should not take it. Dispensed as four blister-packed tablets, its retail cost averages about $500 per package. Check here for current prescribing information.

Another Neupogen Biosimilar Launched

Amneal Pharmaceuticals and its partner, Kashiv BioSciences, have announced the launch of Releuko (filgrastim-ayow), which was FDA-approved on Feb. 25, 2022. A biosimilar for Amgen’s Neupogen^®, it is a colony-stimulating factor (CSF) that promotes the production of neutrophils, key components of the immune system. Releuko’s indications are to decrease infection risk for patients who are undergoing myelosuppressive chemo for non-myeloid cancer, to accelerate neutrophil recovery for patients receiving induction or consolidation chemo for AML, to shorten the duration of neutropenia for patients who are having bone marrow transplants and to mitigate their conditions for patients who have congenital, cyclic or idiopathic neutropenia. Doses, which differ according to the condition being treated, may be injected intravenously (IV) or subcutaneously (SC). Releuko is available in single-dose vials and prefilled syringes each containing either 300mcg/0.5mL or 480mcg/0.8mL. Along with the brand product, two other Neupogen biosimilars,Zarxio^™ (filgrastim-sndz – Sandoz), released to the U.S. market in September 2015, and Nivestym^™ (filgrastim-aafi – Pfizer), introduced in October 2018, also are available in the U.S. For 2021, IQVIA estimates that U.S. sales for all filgrastim products amounted to $407 million, which includes $275 million for biosimilars. Releuko’s full prescribing information can be found here.

Tecentriq’s Bladder Cancer Indication Withdrawn

With the stipulation that further data from ongoing clinical trials confirmed an advantage for using it, Tecentriq^® (atezolizumab) injection was given an Accelerated Approval from the FDA in May 2016. A programmed death receptor-ligand 1 (PD-L1)-blocking antibody made by the Genentech division of Roche, it was approved at that time as initial treatment for some adult patients who have metastatic urothelial carcinoma (bladder cancer). When study results recently showed that Tecentriq was not more effective in extending overall survival (OS) times than chemo for patients in the trial, Genentech decided to withdraw the indication. Genentech will collaborate with prescribers to assure that patients who are being treated with Tecentriq for the withdrawn bladder cancer indication are changed to appropriate alternate therapies. Two other indications — as second-line treatment after chemo for advanced bladder cancer and for triple-negative breast cancer (TNBC) – were withdrawn in 2021. But, it still is FDA approved to treat some melanomas, some liver cancers, some extensive-stage small cell lung cancers (ES-SCLC), and some non-small cell lung cancers (NSCLC). The revised prescribing information will be available here.

Sulfamylon Removed from the U.S. Market

Mylan has stopped the sale of an antimicrobial agent, Sulfamylon^® (mafenide acetate) 5% powder for topical solution, in the United States. It received Accelerated Approval from the FDA in 1998 as part of a therapy regimen to prevent and treat bacterial infections for patients who have second and third-degree burns. Available in packets of powder to be mixed with sterile water for irrigation, it is a sulfonamide antibiotic with wide activity against multiple types of bacteria. A required clinical study to confirm its effectiveness and safety was never conducted by the manufacturer, which now has informed the FDA that running such a trial is “not feasible” considering that the drug has very low sales. Sulfamylon cream, now manufactured by Rising Pharmaceuticals, remains on the market in 60gm tubes and 543.6gm jars.

Withdrawal of Emergency Use Authorization for Bebtelovimab

Because it is ineffective against COVID-19’s Omicron BQ.1 and BQ.1.1 variants, which now cause more than one-half of COVID-19 infections in the U.S., the emergency use authorization (EUA) for Eli Lilly’s bebtelovimab has been rescinded. Lilly received the EUA on Feb. 11, 2022, after data showed the monoclonal antibody was effective for treating the main Omicron variant that was circulating at the time. The FDA announced on Nov. 30, 2022, that Lilly will not distribute any new orders and that the Health and Human Services (HHS) Department’s Assistant Secretary for Preparedness and Response (ASPR) will not fill any pending orders for it. Bebtelovimab presently is not authorized for any use in any part of the country. However, it is being warehoused so that if it proves effective against COVID-19 strains that emerge in the future, its EUA will be reinstated. The FDA advises prescribers that Lagevrio™ (molnupiravir), Paxlovid™ (nirmatrelvir tablets and ritonavir tablets), and Veklury^® (remdesivir) all are appropriate for treating COVID’s Omicron current BQ strains, and they remain available for use across the nation. More information about bebtelovimab and its alternatives is here. Patients and prescribers can use this ASPR website to find nearby locations that offer COVID treatments.