Ukoniq

Former Indications

Ukoniq was previously approved for use in adults to treat specific types of non-Hodgkin lymphoma when the cancer had returned or did not respond to previous therapies. These conditions included:

• Marginal zone lymphoma: For patients who had already received at least one prior treatment that included an anti-CD20 medicine.
• Follicular lymphoma: For patients who had already received at least two prior systemic treatments.

Market Withdrawal

In 2022, the U.S. Food and Drug Administration (FDA) withdrew its approval for Ukoniq. This decision followed a review of clinical trial data that indicated a possible increased risk of death in patients taking the drug. Because the risks were found to outweigh the benefits, the manufacturer voluntarily withdrew the medication from the market. It is no longer available for prescription or use.

Ukoniq works by blocking the activity of specific proteins that help cancer cells grow and multiply. It is classified as a kinase inhibitor, which is a type of drug that interferes with the signaling pathways inside cells.

The medication primarily targets two proteins:

• PI3K-delta: This protein is found in B-cells, a type of white blood cell. In certain lymphomas, this protein is overactive, sending signals that allow cancer cells to survive and spread.
• CK1-epsilon: This protein is involved in regulating cell growth and development.

By inhibiting these proteins, Ukoniq disrupts the life cycle of the cancer cells, making it harder for them to survive and potentially leading to a reduction in tumor size.

Common Side Effects

Many people taking Ukoniq experienced mild to moderate side effects. These may include:

• Nausea and indigestion
• Diarrhea
• Feeling tired or weak (fatigue)
• Muscle or joint pain
• Upper respiratory tract infections
• Skin rash
• Low levels of red blood cells, white blood cells, or platelets

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Serious risks associated with Ukoniq include:

• Severe diarrhea or colitis: Inflammation of the colon that can lead to serious complications.
• Liver toxicity: Changes in liver function tests or liver damage.
• Infections: An increased risk of developing serious infections, such as pneumonia.
• Severe skin reactions: Rashes that may be painful or cover large areas of the body.
• Increased risk of death: Clinical trial findings indicated a higher risk of death in patients treated with Ukoniq compared to those receiving other treatments, which led to the drug's withdrawal from the market.

FDA Withdrawal and Safety Concerns

In April 2022, the FDA withdrew the approval for Ukoniq for the treatment of marginal zone lymphoma and follicular lymphoma. This decision was based on updated findings from the UNITY-CLL clinical trial, which showed that patients receiving Ukoniq had a higher rate of death compared to those in the control group. Because of these safety concerns, the drug is no longer available on the market.

Serious Risks and Side Effects

Before its withdrawal, several serious warnings were associated with Ukoniq use:

• Infections: Serious and sometimes fatal infections, including pneumonia and sepsis, were reported. Monitoring for signs of infection, such as fever or cough, was required.
• Neutropenia: The medication could cause a significant drop in white blood cell counts (neutropenia), which makes it harder for the body to fight infections.
• Diarrhea and Colitis: Severe diarrhea and inflammation of the colon (colitis) occurred in some patients. In some cases, these gastrointestinal issues required hospitalization.
• Liver Toxicity: Ukoniq was linked to hepatotoxicity, characterized by elevations in liver enzymes. Regular blood tests were necessary to monitor liver function.
• Severe Skin Reactions: Some patients experienced serious skin conditions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

Monitoring and Discontinuation

Healthcare providers were instructed to monitor patients closely for any new or worsening symptoms. Following the FDA withdrawal, patients were advised to stop taking Ukoniq immediately and contact their doctor to transition to a different treatment plan.

Pregnancy

Based on findings from animal studies, Ukoniq can cause fetal harm when administered to a pregnant woman. There are no available data on the use of this medication in pregnant humans to inform a drug-associated risk of major birth defects or miscarriage.

Healthcare providers typically recommend the following for individuals of reproductive potential:

• Pregnancy Testing: Females who can become pregnant should have a pregnancy test to confirm they are not pregnant before starting treatment.
• Contraception for Females: Females of reproductive potential should use effective contraception during treatment and for at least one month after the final dose.
• Contraception for Males: Males with female partners of reproductive potential should use effective contraception during treatment and for at least one month after the final dose.

If you become pregnant or think you may be pregnant while taking this medication, contact your healthcare provider immediately.

Breastfeeding

It is not known whether Ukoniq passes into human breast milk or if it affects milk production. Because of the potential for serious side effects in a breastfed child, it is generally advised not to breastfeed during treatment and for at least one month after the last dose.

Patients should discuss the risks and benefits of treatment with their healthcare team to make an informed decision regarding pregnancy and breastfeeding, especially given that the FDA has withdrawn approval for this medication due to safety concerns.

Dosage Forms

Ukoniq was supplied in the following form:

• Oral tablet

This medication is no longer available. The manufacturer voluntarily withdrew Ukoniq from the market, and the FDA withdrew its approval because of data showing a possible increased risk of death in patients taking the drug.

FDA Withdrawal

In June 2022, the U.S. Food and Drug Administration (FDA) officially withdrew its approval for Ukoniq. This action followed a voluntary request from the manufacturer to withdraw the drug from the market after clinical trial data raised significant safety concerns.

Reason for Withdrawal

The withdrawal was based on findings from the UNITY-CLL clinical trial, which evaluated Ukoniq in patients with chronic lymphocytic leukemia. The trial data showed a possible increased risk of death in patients receiving Ukoniq compared to those in the control group. The FDA determined that the risks of the medication outweighed its benefits for its approved uses.

Former Indications

Before its removal from the market, Ukoniq had received accelerated approval to treat adults with:

• Relapsed or refractory marginal zone lymphoma (MZL)
• Relapsed or refractory follicular lymphoma (FL)

Because the drug is no longer approved, it is no longer indicated for these conditions. Healthcare providers were advised to stop prescribing the medication and to transition patients to alternative treatment options.

Regulatory History

Ukoniq was initially granted accelerated approval in February 2021. However, by early 2022, the FDA issued safety communications investigating the increased risk of death and other serious side effects. This investigation eventually led to the voluntary market withdrawal and the formal revocation of FDA approval.

Market Withdrawal and Availability

As of 2022, Ukoniq (umbralisib) is no longer marketed or sold in the United States. The U.S. Food and Drug Administration (FDA) withdrew its approval for the medication after clinical trial data suggested an increased risk of death in patients taking the drug. Consequently, the manufacturer voluntarily withdrew Ukoniq from the market.

Cost and Insurance Information

Because Ukoniq has been removed from the market, there is no current pricing information, and it is no longer covered by insurance providers. Financial assistance programs and co-pay cards that may have existed previously are no longer active. Patients should not attempt to purchase this medication from any source.

Next Steps for Patients

If you were previously prescribed Ukoniq, you should contact your healthcare provider to discuss alternative treatment options. Your medical team can provide information on the costs and coverage for other approved therapies that may be appropriate for your condition.