Third Avastin Biosimilar Approved

Alymsys® (bevacizumab-maly – Amneal Pharmaceuticals) was approved by the U.S. Food and Drug Administration (FDA) on April 13, 2022. A biosimilar to Genentech’s Avastin®, it is a vascular endothelial growth factor (VEGF) inhibitor that is approved for treating some patients who have colorectal (CRC), non-squamous non-small cell lung cancer, glioblastoma, renal cell carcinoma (RCC), cervical cancer, ovarian cancer, fallopian tube cancer or primary peritoneal cancer. It is administered by intravenous (IV) infusion at doses and schedules that differ according to the cancer being treated. Other Avastin biosimilars, Mvasi® (bevacizumab-awwb – Allergan/Amgen) and Zirabev™ (bevacizumab-bvzr – Pfizer) have been on the U.S market since July 2019 and January 2020, respectively. However, none of Avastin’s biosimilars is considered to be a generic and none is automatically interchangeable with Avastin or with each other. For several of their indications, any bevacizumab product should be used along with chemotherapy (chemo). Amneal has not yet announced any pricing plans or a launch date for Alymsys. IQVIA estimated that US sales amounted to $1 billion for Avastin and $1.6 billion for its biosimilars in the 12-month period through the end of February 2022.

First True Generic for Combigan

The first AB-rated generic for Allergan’s Combigan® (brimonidine 0.2%/timolol 0.5%) eye drops was FDA approved on April 4, 2022. Used at a dose of one drop per affected eye roughly 12 hours apart, it treats elevated intraocular pressure (IOP) for patients who are at least two years old. It combines brimonidine, an alpha2-adrenergic receptor agonist, and timolol, a beta-adrenergic receptor inhibitor. Together, they decrease the formation of aqueous humor (the gel that fills the eyeballs) and accelerate the drainage of fluids from the eyes. Sandoz launched the generic immediately at a cost about 10% lower than the wholesale acquisition cost (WAC) for the brand product. An authorized generic (AG) made by Apotex has been available for over three months. In the U.S., Combigan sales were about $373 million for 2021.

Recall

On April 12, the Mylan Pharmaceuticals division of Viatris recalled one lot of Insulin Glargine-yfgn U-100, in 10mL vials. Some vials may not be labeled, which could lead to incorrect doses and episodes of high or low blood sugar. In January, one lot of Semglee® (insulin glargine-yfgn), Viatris’ interchangeable biosimilar to Lantus® (insulin glargine – Sanofi) was recalled for the same reason. However, Semglee is not included in the current recall.

Expanded Yescarta Indication

Yescarta (axicabtagene ciloleucel – Kite, a Gilead Company) won an extension to its approval from the U.S. Food and Drug Administration (FDA) on April 1, 2022. It now is indicated for treating adults who have large B-cell lymphoma (LBCL) that no longer responds to first-line chemotherapy plus immunotherapy (chemoimmunotherapy) or that recurs within one year of chemoimmunotherapy that was used as first-line treatment. A chimeric antigen receptor (CAR)-T therapy, it originally was FDA approved in October 2017 for the treatment of adult patients whose LBCL has returned or become refractory to treatment after two or more lines of systemic therapy. Yescarta also has Accelerated Approval for treating adults who have follicular lymphoma (FL) that has relapsed or become resistant to pharmaceutical therapy following at least two rounds of systemic treatment. Administered only by specially trained health professionals and only in health facilities certified to administer it, Yescarta is produced by collecting and then altering some of the patient’s T cells so that they bind specifically to CD19, an antigen generated by B cells. Processing takes about three weeks. When the modified CAR-T cells are infused back into the patient, they inactivate CD19, destroying the cancerous B cells that produce it. After three days of pretreatment with chemotherapy (chemo), the recommended dose of Yescarta is 2×106 CAR-positive viable T cells/kg of body weight, with an upper limit of 2×108 CAR-positive viable T cells. Because using Yescarta may be associated with potentially fatal neurological side effects and cytokine release syndrome (CRS), it has a patient Medication Guide, boxed warnings, and a risk evaluation and mitigation strategy (REMS). Neurological problems may include confusion headaches, seizures and tremors. CRS is a severe flu-like reaction that can result in cardiac arrest.

Hyftor Receives FDA Approval

The FDA approved Nobelpharma America’s Hyftor™ (sirolimus topical gel) 0.2% on March 22, 2022. Applied twice a day to affected areas, it is indicated to treat facial angiofibromas for patients who have tuberous sclerosis complex (TSC) and who are at least six years old. Believed to affect about 50,000 patients in the U.S., TSC is an inherited condition caused by mutations in specific genes. It results in damage to the eyes and internal organs. The majority of patients have skin lesions that include facial angiofibromas, which begin as tiny red patches and develop into small bumps on the face – usually around the nose and cheeks. Although they are not cancerous, angiofibromas can itch and bleed. They can be embarrassing, reducing the quality of life for patients who have them. Early treatment helps keep them from enlarging. Currently, dermabrasion, laser therapy and surgery are used to manage them. Hyftor is the first drug treatment to be FDA approved for treating angiofibromas on the face. Sirolimus, which also is available in oral forms, is an immunosuppressant that blocks some interleukins, T cell production and antibody formation. In a clinical trial of 62 patients, the size of facial angiofibromas decreased by 75% or more and redness was reduced by three points or more for 10% of those who were treated with Hyftor for 12 weeks. Only 3% of patients using an inactive gel achieved similar results. An additional 13% of actively treated participants had at least some visible improvement, as compared to 3% applying the placebo. Nobelpharma hopes to make Hyftor, which has an Orphan Drug designation for treating facial angiofibromas, widely available within the next few weeks. No cost information has been announced.

Igalmi Approved to Treat Agitation

BioXcel Therapeutics received FDA approval on April 5, 2022, for Igalmi™ (dexmedetomidine), a sublingual formulation of the selective alpha2-adrenergic agonist. Igalmi is indicated as acute treatment for agitation that is related to schizophrenia, bipolar I disorder or bipolar II disorder in adults. In intravenous (IV) form, dexmedetomidine is used to induce and maintain sedation for patients undergoing surgery and for those who are intubated or mechanically ventilated – usually in an intensive care unit (ICU). The new dose form, which can be placed under the tongue or against the inside of the lower lip, will be available in boxes of 10 or 30 individually packaged 120mcg or 180mcg films. Doses depend on the severity of the agitation, the age of the patient and any liver conditions the patient may have. Treatment should be given by a health professional, who can watch the patient for any signs of low blood pressure or other potentially serious adverse effects. The recommended dose is one film dissolved in the mouth. If needed, a second dose may be taken at least two hours after the first and then a third at least two hours later. Because subsequent doses of Igalmi typically are lower than the first, films may be cut in half. No more than a total of 360mcg should be used in any 24-hour period. In clinical studies, either strength initial dose of Igalmi decreased symptoms such as impulsiveness, hostility, tension and excitement within 20 to 30 minutes. Some patients experienced mild-to-moderate side effects that included dizziness, dry mouth, low blood pressure, oral numbness and sleepiness. With plans to introduce Igalmi in the second quarter of 2022, BioXcel has not yet announced pricing.

Aduhelm Coverage Limited

On April 7, 2022, the Centers for Medicare and Medicaid Services (CMS) released its policy on Medicare coverage for anti-amyloid monoclonal antibodies that are used to treat Alzheimer’s disease. In line with its draft strategy, CMS will cover drugs in the class, including Aduhelm™ (aducanumab – Biogen/Eisai), under Medicare Part B, but only if they are fully FDA approved as safe and effective. Because Aduhelm, the only one currently available in the U.S., received the FDA’s Accelerated Approval based on interim results from unfinished clinical trials in June 2021, its results must be verified in ongoing studies before full approval is granted. Medicare will cover the cost of treatment for patients who are enrolled in those studies, as well as for participants in National Institute of Health (NIH) or FDA-approved trials for other amyloid-focused antibodies that are still in development. It will not reimburse for anti-amyloid antibody treatment for individuals who are not in approved clinical trials.