Xaciato Gets FDA Approval

Daré Bioscience received approval from the U.S. Food and Drug Administration (FDA) on Dec. 7, 2021, for its first product, Xaciato™ (clindamycin phosphate) vaginal gel, 2%. It is an antibacterial that is indicated to treat bacterial vaginosis for patients at least 12 years old. Given intravaginally in a single dose, it is dispensed in disposable applicators containing 100mg of clindamycin. Caused by an overabundance of natural vaginal bacteria, vaginosis is estimated to affect about 21 million women between the ages of 14 years and 49 years in the U.S. Although about one-half of patients have no or only mild symptoms, it can cause vaginal secretions that have a distinctive smell, as well as itching or pain in the vagina. Several other clindamycin agents and other antibacterials, such as metronidazole, are available in both topical and oral formulations to treat bacterial vaginosis. About four out of five women who have been treated experience another bacterial vaginosis infection within 90 days of treatment, however. In clinical studies, Xaciato had cure rates up to 80% as compared to between 37% and 68% for current standard treatments. Approved under the FDA’s Fast-Track process, Xaciato also was designated as a Qualified Infectious Disease Product (QIDP), bringing its exclusivity period to eight years. Pending the selection of a marketing partner, launch is expected in 2022 at a cost that is yet to be determined.

FDA approves Lyvispah

Long available as oral tablets, the skeletal muscle relaxer, baclofen, was approved by the FDA in a new formulation on Nov. 22, 2021. Saol Therapeutics received approval for Lyvispah™ (baclofen) oral granules to treat patients who are 12 years old or older for spasticity caused by multiple sclerosis (MS). Noting that it also may be helpful for some patients who have spinal cord injuries, Saol states that Lyvispah is particularly effective for relieving pain and rigidity due to flexor spasms (muscle cramps at the ankles, knees and hips). In 2022, Lyvispah will be available in packets containing 5mg, 10mg or 20mg of baclofen. Directions are to dissolve the granules in the mouth or mix them with about a tablespoon of liquid or soft food and swallow them. Doses begin at 5mg three times daily, then increase by 5mg per dose at three-day intervals to the recommended maintenance level of three 20mg doses daily. Some patients may need the maximum dose recommended of 80mg taken in four equal 20mg parts daily. Cost has not yet been made public.

Emergency Use Authorized for Evusheld

A combination of new long-acting monoclonal antibodies, Evusheld™ (tixagevimab 150mg co-packaged with cilgavimab 150mg) was granted an emergency use authorization (EUA) by the FDA on Dec. 8, 2021. It is the first drug indicated to prevent COVID-19, and it will be used for immunocompromised patients who are 12 years old or older, who weigh 40kg (88 pounds) or more and who have not been exposed to COVID-19. Patients who cannot be fully vaccinated against COVID-19 due to a severe reaction to the vaccine also are candidates for use of Evusheld. It is not approved to treat the infection or to prevent COVID-19 after exposure to it. Unlike the intravenously (IV) infused monoclonal antibodies that treat COVID-19, Evusheld will be administered as separate intramuscular (IM) injections of one antibody followed closely by the other. In the PROVENT clinical trial, the chance of developing a COVID-19 infection within six months was 83% lower for patients who received Evusheld injections than for patients who got placebo injections. Whether injections will be needed more than one time is not yet known. AstraZeneca plans to release doses of Evusheld as soon as possible, but no exact date is available. Fact Sheets for its use are here for healthcare providers and here for patients and caregivers.

Emergency Use Extended for Bamlanivimab with Etesevimab

Originally issued in February 2021, the EUA for Eli Lilly’s antibody combination, bamlanivimab with etesevimab, was expanded on Dec. 3, 2021. Now, it includes children, including new babies, who are at high-risk for severe cases of COVID-19. It can be used to treat mild-to-moderate COVID-19 and to prevent it after known exposures. Patients hospitalized for COVID-19 and those who need oxygen to treat it should not be given bamlanivimab with etesevimab, and it is not available in areas that have more than 5% of resistant variants. The FDA maintains a list of allowed locations here. Look here for the revised Provider Fact Sheet and here for the Patient/Caregiver version.

New Ages Added to Eligibility for a Comirnaty Booster

The EUA for Pfizer/BioNTech’s COVID -19 vaccine, Comirnaty® (COVID-19 vaccine, mRNA), also has been expanded. On Dec. 9, 2021, the FDA included 16- and 17-year olds in the range of individuals eligible for boosters with the vaccine. Six months or longer after their last dose of any FDA-approved COVID-19 vaccine, 16-year olds and 17-year olds now can receive one booster dose of Comirnaty. No other COVID-19 vaccine currently has EUA in the U.S. as a booster for patients under the age of 18. Here is the updated Comirnaty Provider Fact Sheet and here is one for Patients and Caregivers.

Rituxan’s Indications Extended

On Dec. 2, 2021, the FDA approved Biogen/Genentech’s Rituxan® (rituximab) injection as first-line treatment along with chemotherapy (chemo) of patients as young as six months old for four cancers. It now can be used for children and teens who have advanced cases of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, Burkitt-like lymphoma or mature B-cell leukemia. Doses for pediatric patients are administered at 375mg/m2 in six IV infusions – four during induction phases of therapy and two more during consolidation phases. A boxed warning for Rituxan cautions that some patients have died as a result of infusion reactions – usually within the day after the first dose. It also may cause reactions on the skin and mucous membranes, and very rare cases of brain damage due to progressive multifocal leukoencephalopathy (PML). Since using it may rekindle hepatitis B virus (BV), patients using it should be tested for HBV before and during therapy. They should have regular complete blood counts (CBC), too. Rituxan is given by intravenous (IV) infusions in healthcare facilities that can manage any reactions that may occur. Its previous FDA indications include treating adults who have non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA) and pemphigus vulgaris (PV). It also is approved to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for both adults and children age two and older. Look here for updated prescribing information.

FDA Approves Keytruda to Treat Stage II Melanomas

Merck’s programmed death receptor 1 (PD-1) inhibiting immunotherapy, Keytruda® (pembrolizumab), was FDA approved on Dec. 3, 2021, for the treatment of patients who are at least 12 years old and who have stage IIB or IIC melanoma. Its indication for stage III melanoma also was broadened to include patients age 12 and older. For adults, it will be used as an adjuvant (post-surgical tumor removal) therapy at a dose of 200mg once every three weeks or 400mg once every six weeks. Pediatric doses are calculated according to the patient’s weight at 2mg/kg (but no more than 200mg) and given once every three weeks. Administered as a 30-minute IV infusion, Keytruda is used alone or in combination with one of several other oncology drugs for multiple previous indications that include treating some esophageal, head and neck, kidney, lung and stomach cancers; as well as Merkel cell carcinoma (MCL) and non-Hodgkin lymphoma (NHL). It also treats cancers that have specific genetic characteristics (biomarkers), rather than developing from a particular body tissue. Here is its full, revised prescribing information.

Pediatric Indication and Flexible Dosing for Cutaquig

Cutaquig ® (immune globulin subcutaneous [human] – hipp), 16.5% solution, was approved in 2018 to treat adults who have primary humoral immunodeficiency (PI). On Dec. 7, 2021, its manufacturer, Octapharma, announced that its use has been extended to treat PI for children as young as two years old. A group of inherited conditions that involve a partial or nonfunctioning immune system, PI predisposes patients to have serious, chronic and/or recurrent infections. Cutaquig is administered subcutaneously (SC) to replace missing natural immunoglobulin (IG). Doses of Cutaquig depend on the patient’s blood levels of IG. The FDA also approved giving Cutaquig on varying schedules ranging from small doses once a day to larger ones once every two weeks depending on the response to therapy, the prescriber’s clinical judgement and the patient’s preference. A boxed warning that using any IG product can cause blood clots is required on the labeling of all IG replacements. Check here for Cutaquig’s complete prescribing information.

Zynrelef Gets New Approvals

Heron Therapeutics received additional FDA approvals on Dec. 8, 2021, for its combination of a local anesthetic and a non-steroidal anti-inflammatory drug (NSAID), Zynrelef® (bupivacaine/meloxicam) extended-release solution. It is given as one dose instilled into the soft tissue around a surgical site or joint to relieve pain for as long as 72 hours. Originally FDA approved in May 2021, it initially was indicated for adult patients following surgery for removing bunions, repairing inguinal hernias or replacing knee joints. Its indications now include for foot and ankle operations, small-to-medium open abdominal procedures and lower extremity total joint arthroplasties. Products that contain a prescription-strength NSAID have boxed warnings about possibly life-threatening blood clots and gastrointestinal (GI) side effects that may be associated with using them. Zynrelef should not be used for patients under the age of 18 or for patients having coronary artery bypass grafts (CABG). Its current prescribing information may be found here.

Withdrawal for One Copiktra Indication

Copiktra® (duvelisib) capsules, is an oral phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma inhibitor with a recommended dose of 25mg twice daily. With the stipulation that post-marketing clinical trial results confirmed its preliminary benefits, the FDA gave it Accelerated Approval in September 2018 for treating adults who have follicular lymphoma (FL). After considering the other therapies that are available to treat FL and the obstacles that are involved in conducting clinical trials, Secura Bio, the present manufacturer of Copiktra has made the business decision to withdraw the drug’s indication for FL. The drug’s effectiveness and safety are not factors in the withdrawal. Secura Bio is working with the FDA and with physicians to assure that patients taking Copiktra for FL are moved to other appropriate therapies. Copiktra’s full FDA approval as third-line therapy for adult patients who have relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is not affected. It will remain available for that indication and it is in clinical studies for treating peripheral T-cell lymphoma (PTCL), and several other blood cancers, as well as some solid tumors. A boxed warning on the labeling for Copiktra and an associated Risk Evaluation and Mitigation Strategy (REMS) outline the possibility for potentially deadly infections, diarrhea, colitis, skin reactions and pneumonitis that may be associated with its use. Here is prescribing information.