On Feb. 4, 2022, the U.S. Food and Drug Administration (FDA) approved Sanofi’s Enjaymo™ (sutinlimab – jome), the first therapy specifically indicated for treating adults who have cold agglutinin disease. A rare type of autoimmune disorder, cold agglutinin disease causes red blood cell (RBC) hemolysis – meaning that RBCs disintegrate faster than normal. Patients develop anemia and other symptoms when they encounter air temperatures that are lower than about 40˚F. To treat it, Enjaymo will be administered by intravenous (IV) infusions at a dose of 6,500mg (six vials) for patients who weigh between 39kg (about 86 pounds) and 75kg (165 pounds) or 7,500mg (seven vials) for those weighing more. The first two doses are given one week apart, then they change to once every two weeks. Wholesale acquisition cost (WAC) is $1,800 per vial. An exact launch date is not yet available, but it is expected in the coming weeks. Here is prescribing information.
At a Glance
- Brand (Generic) Name: Enjaymo (sutinlimab – jome)
- Manufacturer: Sanofi, which bought the original developer, Bioverativ Therapeutics
- Date Approved: Feb. 4, 2022
- Indication: to decrease the need for RBC transfusions due to hemolysis in adults who have cold agglutinin disease
- Dosage Forms Available: single-dose vials containing 1,100mg of Enjaymo in 22mL of solution for reconstitution and IV infusion
- Launch Date: Within the coming weeks
- Estimated Annual Cost: After the first year, which needs one additional vial, yearly WAC for a patient who weighs less than 75kg is about $281,000; for a patient who weighs 75kg or more, about $328,000.
- In the U.S., approximately one adult per one million – or roughly 260 individuals – is diagnosed with cold agglutinin disease each year. Patients mostly are 40 years old or older. About two-thirds are women and around 70% of patients have predisposing factors such as some types of cancer or an inflammatory disease.
- Symptoms may be mild, but they can include dark urine, dizziness, fatigue, jaundice and pale skin. Premature destruction of RBCs often causes low hemoglobin, the protein that transports oxygen throughout the body.
- Typically, RBCs survive for around four months before they wear out. For patients who have cold agglutinin disease, a normal antibody, immunoglobulin M (IgM), incorrectly attacks RBCs when patients are exposed to temperatures below about 40˚F. As a result, RBCs form clusters that attract proteins known as complements and other components of the immune system, which cause the cells to degrade too early.
- Currently, no other drug is FDA approved to treat cold agglutinin disease. Rituximab, a cancer drug, may be used off label along with certain chemotherapy (chemo) drugs or prednisone for patients with severe symptoms.
- Many patients need blood transfusions or plasma exchanges if RBCs are destroyed too rapidly.
- By inhibiting complement 1 (C1), Enjaymo decreases the destruction of red blood cells.
- In the CARDINAL clinical trial, all 24 patients received Enjaymo infusions for 26 weeks. Fifteen patients had increases of at least 2gm/dL in hemoglobin, 17 did not need transfusions and 22 did not need any additional treatment.
- Side effects included infections, diarrhea, coughing, aching and swollen hands and feet.
- Designated as an Orphan Drug, Enjaymo was approved under the FDA’s Breakthrough Therapy and Priority Review processes.
Vaccine, Spikevax, Gains Full FDA Approval
On Jan. 31, 2022, full U.S. Food and Drug Administration (FDA) approval was granted to Moderna’s Spikevax (COVID-19 vaccine, mRNA) injection for patients 18 years of age and older. The vaccine, which has been available in the U.S. under Emergency Use Authorization (EUA) since Dec. 18, 2020, was fully approved with Priority Review, well ahead of schedule. Marketed as Spikevax™, it is given as a primary series of two 100mcg (0.5mL) intramuscular (IM) injections spaced one month apart — the same dosage and schedule as in the EUA version. Approval was based on real world data that supports the total submission package provided by the company. In the decisive clinical trial, the vaccine was shown to be over 93% effective for preventing COVID-19. On Nov. 19, 2021, Moderna’s vaccine was given EUA as a single shot booster for individuals who are at least 18 years old. Administered five months or more following the primary series, the booster dose is one-half of the primary series dose (50mcg). For full prescribing information see here. The factsheet for caregivers and patients can be viewed here. And for prescribers the factsheet is here.
New Indication for Vonvendi
Takeda’s Vonvendi® (von Willebrand factor [recombinant]) won FDA approval on Jan. 30, 2022, for regular use to decrease bleeding in patients at least 18 years old who have severe cases of type 3 von Willebrand’s disease (VWD) and who are being treated on an as-needed basis for bleeding episodes. Similar to hemophilia, VWD results from the deficiency of a blood protein that helps blood to clot normally. Unlike hemophilia, however, VWD disease affects about twice as many women as men – with an estimated total of 3.2 million patients in the U.S. Type 3, the most severe form of the condition, is also the rarest form, affecting only around 3% of patients. Vonvendi, which was FDA approved in December 2015, to treat and control bleeding episodes for patients who have VWD, also has an indication to manage perioperative bleeding for adult patients who have VWD. Administered by IV infusion, doses are determined by the patient’s weight and levels of specific blood factors. For prevention, the recommended dose is 40IU/kg to 60IU/kg two times a week. Additional doses may be needed for breakthrough bleeding events. Prescribing information for Vonvendi is here.
FDA Approves New Dosing Schedule for Cabenuva
After an additional FDA approval that was granted on Jan. 31, 2022, Cabenuva (cabotegravir extended-release injection and rilpivirine extended-release injection) now can be administered once every two months. The only long-acting drug combination for treating HIV-1, it originally was approved a year ago to be given once each month. Cabenuva is used for adult patients who have had no failures with previous HIV-1 treatment and whose viral load is less than 50 copies of HIV-1 RNA/mL due to a current stable anti-HIV-1 regimen. It is dispensed in boxes containing single-dose vials of each cabotegravir and rilpivirine. They are given as separate intramuscular (IM) injections by a health professional in a healthcare setting. The dose for the new schedule is 600mg of cabotegravir and 900mg of rilpivirine beginning on the last day of a one-month-long course of lead-in dosing with the oral HIV-1 drugs Vocabria (cabotegravir – ViiV Healthcare) tablets and Edurant® (rilpivirine – Janssen) tablets taken daily. The first two injected doses are given one month apart before dosing switches to once every two months. Look here for Cabenuva’s full prescribing information.
First Generic Approved for Restasis
On Feb. 2, 2022, Mylan received approval from the FDA for cyclosporine ophthalmic emulsion, 0.05%, in single-use vials. An immunomodulator, it stimulates tear production by decreasing eye inflammation that probably results from keratoconjunctivitis sicca (dry eye disease). An estimated 16.4 million Americans who are 18 years old and older have been diagnosed with dry eye disease. About twice as many women as men are affected and incidence increases with age. The condition causes blurred vision, light sensitivity and burning, irritated, red and/or scratchy eyes. No launch date or pricing information have been announced, yet, for the generic. Mylan is not expected to have an exclusivity period because several other generic companies may have settlement agreements from legal challenges of Restasis patents. Some manufacturers may be able to introduce authorized generics, as well. The multi-dose bottle of Restasis has a unique cap, filter and valve system that is patent protected until 2034. It remains brand only.
Zohydro ER Discontinued
Most recently marketed by Currax Pharmaceuticals, Zohydro® ER (hydrocodone extended-release capsules) has been removed from sale in the United States. A C-II controlled substance, it was FDA approved in 2013 as the only single-ingredient hydrocodone product for managing severe pain that needs continuous, long-term treatment and that has not responded to prior treatment. In 2015, it was reformulated to incorporate a proprietary technology called BeadTek™ that creates thick, sticky goo if the capsules are opened or crushed and the contents dissolved in liquids or solvents. Its use still was problematic, including lawsuits when some states attempted to ban its use at a state level. Now, the manufacturer has stopped distributing Zohydro ER and the FDA rescinded approval for it effective in late February. Any patients who have been taking it should be switched to another pain reliever.
Numerous Prescription Drugs Withdrawn from Sale
In addition to Zohydro, FDA approval for 28 other drugs also is being retracted. The manufacturers of the products have asked the FDA to discontinue approval because the drugs are no longer sold in the U.S. The withdrawals are for business reasons, such as low sales, not for effectiveness or safety issues with the drugs. They comprise a variety of infrequently used products that include some pain relievers, a few eye drops and a couple of topical antimicrobial skin cleansers. Products currently in stock at wholesalers or retail pharmacies can still be sold until supplies run out or the products reach their expiration dates. Patients can keep using any of the withdrawn products that they may have on hand, but they will need to consult with their prescribers for alternate treatments if they need to continue care. A full list of affected drugs is here.
Updated “COVID Vaccines” Issues Document Available
The Emerging Therapeutics department has updated the “Coronavirus Disease 2019 (COVID-19) Vaccine Update” issues document. The revision includes full FDA approval of Moderna’s Spikevax.
Empowered Diagnostic’s COVID-19 Tests
The FDA released a safety communication on Jan. 28, 2022, concerning COVID-19 testing kits made by Empowered Diagnostics. The tests, CovClear COVID-19 Rapid Antigen Test and ImmunoPass COVID-19 Neutralizing Antibody Rapid Test, have not been evaluated or authorized by the FDA. They may be more likely than approved tests to deliver inaccurate results. Empowered Diagnostics is removing them from distribution in the U.S. New tests are not necessary for all patients. However, testing sites are advised to consider repeating antigen tests given less than two weeks previously or antibody tests, if the initial results from one of the Empowered Diagnostics’ tests are in question. More information can be found in an FDA notice here.
In another safety communication that was posted on Feb. 3, 2022, the FDA warned about possibly increased risks of death among patients who take Ukoniq® (umbralisib) tablets. A kinase inhibitor, Ukoniq blocks the action of two different enzymes, phosphoinositide 3 kinase (PI3K)-delta and casein kinase 1 (CK1)-epsilon. Its indications are to treat adults whose cancer has returned or become resistant to treatment despite previous therapy with a CD20 inhibitor for marginal zone lymphoma (MZL) or with at least three systemic therapies for follicular lymphoma (FL). Until further evaluations are completed, the FDA has stopped new patients from entering ongoing clinical trials. Patients who are taking Ukoniq should discuss different treatment options with the physicians who prescribed it. Check here for more information.
Genentech received approval from the U.S. Food and Drug Administration (FDA) on Jan. 28, 2022, for Vabysmo™ (faricimab-svoa) injection. A bispecific (affecting two separate antigens) antibody, it is indicated to treat both neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME). A 6mg dose will be injected into the affected eyes by a healthcare professional. Separate vials should be used if the patient needs injections in both eyes. After patients receive their first four treatments at four-week intervals, dosing can be adjusted to once every eight, 12 or 16 weeks for AMD or once every four or eight weeks for DME, depending on the patient’s response to therapy. Launch is planned in the next few weeks at a wholesale acquisition cost (WAC) of $2,190 per dose (each treated eye). Full prescribing information is here.
At a Glance
- Brand (Generic) Name: Vabysmo (faricimab-svoa) injection
- Manufacturer: Genentech
- Date Approved: Jan. 28, 2022
- Indication: treatment of nAMD and DME
- Dosage Forms Available: single-dose vials containing 0.05mL of a 120mg/mL solution for intravitreal (back of eye) injection
- Launch Date: in the coming weeks
- Estimated Annual Cost: WAC is $2,190 per dose. Total cost will depend on whether one or both eyes are treated and dosing intervals that are appropriate for each individual patient.
- An estimated 1.1 million Americans have nAMD, which distorts central vision. It is caused by abnormal growth of blood vessels in the maculas, the parts of the retinas responsible for clear central vision. Roughly 40% of cases involve both eyes at diagnosis, but up to 20% of patients progress to bilateral involvement each year. Approximately 750,000 patients have DME, which results from swelling due to blood seeping from damaged blood vessels in the macula. DME is more likely to affect both eyes — as many as 80% of patients at diagnosis. Without treatment, either condition can lead to blindness.
- Both conditions are diseases of aging, with most patients in their 60s or older. AMD is more common for patients who have cardiovascular (CV) disease, hypertension, light-colored eyes and/or obesity. DME may be diagnosed for more middle-aged adults than nAMD does, and it is more prevalent for patients who have had diabetes for long periods and/or whose diabetes is not well controlled.
- Vabysmo blocks the activity of neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), to decrease blood seepage and inflammation in the eyes by strengthening blood vessels.
- VEGF inhibitors currently approved to treat one or both eye conditions include Eylea® (aflibercept – Regeneron), Lucentis® (ranibizumab – Genentech) and Beovu® (brolucizumab-dbll – Novartis). In addition, Avastin® (bevacizumab – Genentech) is used off-label for certain eye conditions. Indications and dosing intervals among these products vary.
- In two completed phase III clinical trials of Vabysmo, which included 1,300 patients who had new diagnoses of nAMD, results after two years of using Vabysmo administered either once every eight, 12 or 16 weeks were comparable to those from Eylea given once every eight weeks. At the beginning of each study, loading doses of both drugs were given monthly for four doses (Vabysmo) or five doses (Eylea). Two additional clinical studies that involved about 1,900 patients who had DME also tested Vabysmo against Eylea for two years. After four or six monthly loading doses, Vabysmo was given once every eight, 12 or 16 weeks, based on the patient’s response to treatment. Eylea was administered once every eight weeks following five monthly doses. Again, the effectiveness and safety of Vabysmo were comparable to those of Eylea.
- About 7% of patients using Vabysmo in clinical trials had transient hemorrhages in the conjunctiva (the membrane lining the fronts of the eyes and the eyelids) making the white parts of the eye look red. Other mostly mild and temporary side effects included floaters, increased intraocular pressure and temporary eye pain.