Drug Injury Watch

Novartis Finally Issues Revised Beovu Prescribing Information for US in February 2022

Meaning as Regards Beovu Safety Issues by a Comparison of Major Changes Made: "Revised: 2/2022" vs. "Revised: 6/2020"

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Beovu (brolucizumab) was approved by the FDA in 2019 as a treatment for neovascular (wet) age-related macular degeneration (AMD). Since then, there have been reported cases of Beovu eye-related side effects such as retinal vasculitis, retinal vascular occlusion, or retinal artery occlusion leading to vision loss. We have followed these Beovu safety issues for the past two years here on Drug Injury Watch, with our first article dating back to February 2020 (see: "Beovu Side Effects Include Retinal Vasculitis, Eye Inflammation: Safety Issues For Macular Degeneration Drug").

Most recently we have been watching for a forecasted Beovu label change which would, presumably, add new and updated warnings about Beovu eye-related side effects. Now, in February 2022, there is finally a revised Beovu drug label here in the US.

We use the word "finally" because it was back in May 2021, when Novartis stopped three Beovu clinical trials for safety reasons, that Novartis first said it would update the Beovu drug label (see: "Beovu Vision Loss Side Effects Continue to Plague Novartis, Ending 3 Key Clinical Trials in May 2021").  Further, over in Europe, Novartis sent out a November 2021 “Dear Doctor” Letter about Beovu, which was followed by an MHRA January 2022 Drug Safety Update item for Beovu that stated:

New information on [the Beovu adverse events retinal vasculitis and retinal vascular occlusion], including risk factors and possible mechanism, was considered in a recent European safety review and ophthalmologists were informed of the new recommendations in a letter in November 2021. The product information of [Beovu (brolucizumab)] will also be updated to reflect this information.

You can learn more about this first Beovu drug label change made after what Novartis did and said back in May 2021 by taking a look at this recent Drug Injury Watch article, "Beovu Drug Label Change in December 2021 Adds More Information About Vision Loss Side Effects".

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So that people can draw their own conclusions about what this February 2022 Beovu label change means as regards the lingering Beovu safety issues mentioned at the outset, we will present a comparison of the Beovu Prescribing Information "Revised: 2/2022" document  (PDF) with the earlier "Revised: 6/2020" version, limited to those three parts identified in the "Recent Major Changes" section of the new 2022 Beovu drug label.

 

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CHANGE (February 2022) -- 5.2 Retinal Vasculitis and/or Retinal Vascular Occlusion

Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU. These immune mediated adverse events may occur following the first intravitreal injection. Discontinue treatment with BEOVU in patients who develop these events. Patients treated with BEOVU who experience intraocular inflammation may be at risk of developing retinal vasculitis and/or retinal vascular occlusion and should be closely monitored [see Contraindications (4.2) and Adverse Reactions (6.1, 6.2)]. Patients should be instructed to report any change in vision without delay.

 

COMPARE (June 2020) -- 5.2 Retinal Vasculitis and/or Retinal Vascular Occlusion

Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU [see Contraindications (4.2) and Adverse Reactions (6.1)]. Patients should be instructed to report any change in vision without delay.

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ADDED (February 2022) -- 6.1 Clinical Trials Experience (as a final paragraph, below Table 1)

In a clinical study (MERLIN), patients with nAMD who received BEOVU every 4-week maintenance dosing experienced a higher incidence of intraocular inflammation (including retinal vasculitis) and retinal vascular occlusion than patients who received BEOVU every 8 or 12-week maintenance dosing in the clinical studies (HAWK and HARRIER). The interval between two BEOVU doses during maintenance treatment should not be less than 8 weeks.

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CHANGE (February 2022) -- 6.2 Immunogenicity (final two paragraphs)

Anti-brolucizumab antibodies were detected in the pre-treatment sample of 36% to 52% of treatment naive patients. After initiation of dosing, anti-brolucizumab antibodies were detected in at least one serum sample in 53% to 67% of patients treated with BEOVU. Intraocular inflammation was observed in 6% of patients with anti-brolucizumab antibodies detected during dosing with BEOVU. Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, are immune mediated adverse events related to exposure to BEOVU. This treatment emergent antibody response may develop following the first intravitreal injection.

Anti-brolucizumab antibodies were not associated with an impact on clinical efficacy.

 

COMPARE (June 2020) -- 6.2 Immunogenicity (final two paragraphs)

Anti-brolucizumab antibodies were detected in the pre-treatment sample of 36% to 52% of treatment naive patients. After initiation of dosing, anti-brolucizumab antibodies were detected in at least one serum sample in 53% to 67% of patients treated with BEOVU. Intraocular inflammation was observed in 6% of patients with anti-brolucizumab antibodies detected during dosing with BEOVU.

The significance of anti-brolucizumab antibodies on the clinical effectiveness and safety of BEOVU is not known.

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We will continue to monitor the drug safety regulatory sector for further developments concerning Beovu eye-related side effects such as retinal vasculitis, retinal vascular occlusion, and retinal artery occlusion.

As we have reported previously, starting in January 2021, Beovu lawsuits have been filed for patients alleging that Novartis failed to warn doctors and patients about these Beovu vision loss side effects in a timely manner.

We continue to investigate Beovu drug injury lawsuits against Novartis where there has been vision loss due to retinal vasculitis, retinal vascular occlusion, or retinal artery occlusion after patients received their Beovu injections.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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How People Can Report Adverse Drug Reactions to the FDA, and What Happens to This Information Thereafter

A Brief Introduction for Patients to (1) the FDA MedWatch Program, and (2) the FDA Adverse Event Reporting System

 

(Posted by Tom Lamb at Drug Injury Watch)

 

From time to time we hear from people who want to know:

(1) How they can report a serious prescription drug side effect, or adverse drug reaction, to the FDA; and,

(2) What happens to the information that they submit to the FDA.

Here is a brief introduction to the FDA MedWatch Program and the FDA Adverse Event Reporting System, which are parts of our answers to those questions.

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FDA MedWatch Program

MedWatch is an FDA program for reporting “serious reactions” resulting from a prescription medication. The FDA is particularly interested in those drug injury events which resulted in any of the following outcomes:

• Patient's Death: an adverse reaction to a drug is the suspected cause of death
• Life-Threatening Condition: a serious side-effect put the patient at real risk of dying
• Hospitalization: the person is admitted to the hospital because of their serious adverse reaction to a medication
• Permanent Disability: strokes; nervous system disorders; other impairment
• Birth Defect or Birth with Disease: congenital anomaly; adverse outcome to a child
• Needs Medical Intervention to Avoid Permanent Damage: medical treatment is required

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How to File a MedWatch Report

The FDA encourages patients to take the Reporting Form to their treating doctor when it is known or suspected that they have been seriously harmed by a pharmaceutical product. However, it is important to understand that this physician is not required to make a report to the FDA, even if you ask them to do so.

For this reason, and because there may be circumstances when a person does not want to go back to their doctor to ask for help with a drug injury report, patients can submit their information directly to the FDA. There is an online reporting form available through the FDA website.

To report online, you can use the MedWatch Online Voluntary Reporting Form (3500).

Form FDA 3500B (a PDF form that can be filled out online) is a consumer-friendly voluntary reporting form that contains less technical language than the online FDA Form 3500.

MedWatchLearn is a web-based learning tool designed to educate medical students, doctors or other health professionals, and consumers on reporting in a way that provides the best information for FDA reviewers to further investigate medical product problems.

Lastly, you can use the toll-free telephone number for reporting a suspected drug injury to the FDA: 800-FDA-1088.

Be assured that the patient’s identity will be held in strict confidence by the FDA. In addition, the FDA will not disclose the identity of the person who submitted the report, be it the doctor, the patient, a family member, a health care provider, or some other concerned person.

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FDA Adverse Event Reporting System

The United States Food and Drug Administration (US FDA) has established a drug safety database known as the FDA Adverse Event Reporting System (AERS).

The basic information stored in the AERS is taken from the Individual Safety Report (ISR), which contains all of the information contained on the MedWatch form (FDA Form 3500 or FDA Form 3500A). ISRs can be submitted to the FDA by consumers, health care providers, and drug manufacturers. A real limitation to the database, however, is under-reporting. One study found that only 1% of serious adverse events are reported to the FDA.

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JAK Inhibitors Safety Review by European Drug Regulator EMA Announced in February 2022

Xeljanz, Rinvoq, and Olumiant as Treatments for Inflammatory Disorders Have Been Under Scrutiny by FDA in the US

 

(Posted by Tom Lamb at Drug Injury Watch)

 

In December 2021 there was a notable JAK inhibitors drug class safety development in the US, with Xeljanz, Olumiant, and Rinvoq getting revised drug labels with more side effects warnings and more drug use restrictions. These December 2021 JAK inhibitors label changes were “new” but anticipated because back in September 2021 the FDA announced that it was requiring revisions to the “Black-Box” warnings already on the drug labels for Xeljanz, Olumiant, and Rinvoq “to include more information about the risks of serious heart-related events, cancer, blood clots, and death.”

Now the issue of JAK inhibitors drug class safety is coming up in Europe, as indicated by this European Medicines Agency (EMA) February 11, 2022, news item, "EMA starts safety review of Janus kinase inhibitors for inflammatory disorders".

Consistent with the December 2021 JAK inhibitors label changes mandated by the FDA here in the US, Xeljanz, Rinvoq, and Olumiant as treatments for inflammatory disorders are the subject of this JAK inhibitors safety review announced by the EMA in February 2022.

From the above-referenced EMA news item:

The review was prompted by the final results from a clinical trial (study A3921133) of the JAK inhibitor Xeljanz (tofacitinib). The results showed that patients taking Xeljanz for rheumatoid arthritis and who were at risk of heart disease were more likely to experience a major cardiovascular problem (such as heart attack, stroke or death due to cardiovascular disease) and had a higher risk of developing cancer than those treated with medicines belonging to the class of TNF-alpha inhibitors....

In addition, preliminary findings from an observational study involving another JAK inhibitor, Olumiant (baricitinib), also suggest an increased risk of major cardiovascular problems and VTE in patients with rheumatoid arthritis treated with Olumiant compared with those treated with TNF-alpha inhibitors.

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During this past 12 months, to the day, we have written these 12 earlier Drug Injury Watch articles which are relevant to Xeljanz, Rinvoq, and Olumiant, given that they are about JAK inhibitors drug class safety and JAK inhibitors label changes:

1. Xeljanz FDA Drug Safety Communication in February 2021 Puts Heightened Scrutiny on Pfizer (February 11, 2021)
2. Xeljanz Has A New Drug Safety Issue, We Just Don't Know How Significant It Is, Yet (February 17, 2021)
3. Possible Ramifications of Recent FDA Alert About Xeljanz Heart Problems and Xeljanz-related Cancers (March 23, 2021)
4. Xeljanz and Other JAK Inhibitors: Drug Safety Concerns Indicated by Recent FDA Actions (April 15, 2021)
5. Possible FDA Advisory Committee Meeting for Xeljanz, Rinvoq, and Other Janus Kinase (JAK) Inhibitors (July 6, 2021)
6. Xeljanz: FDA Warnings Updated: There are Higher Rates of Blood Clots and Deaths for Both Doses of Xeljanz, Now (September 1, 2021)
7. Xeljanz: Drug-induced Peripheral Neuropathy as Possible Xeljanz Side Effect in 2 RA Patients (September 29, 2021)
8. Xeljanz Risks of Cardiovascular Events, as well as Cancers, Cause More Xeljanz Use Limitations (October 12, 2021)
9. Eli Lilly Attempts to Distance Olumiant From the Ominous JAK Inhibitors Drug Class Safety Issues Flagged by FDA (November 29, 2021)
10. December 2021 JAK Inhibitors Drug Class Label Changes: More Warnings and Use Restrictions (December 9, 2021)
11. Xeljanz Link to Cancers, Heart Attacks, Strokes, and Cardiovascular Deaths is Confirmed by Health Canada in January 2022 (January 14, 2022)
12. Xeljanz Safety Study Final Data Details the Increased Risks of Cancers and Major Adverse Cardiovascular Events (January 31, 2022)

Our law firm is investigating possible drug injury lawsuits involving Xeljanz, Rinvoq, and Olumiant for patients who have suffered serious side effects or adverse drug reactions. Feel free to contact us if you or someone you know might have a Xeljanz, Rinvoq, or Olumiant drug injury case. 

To learn more, you can visit the Xeljanz | Rinvoq | Olumiant Side Effects page on our Drug Injury Law website.

And, of course, we will continue to watch for future developments related to JAK inhibitors drug class safety and JAK inhibitors label changes, as we have done during the past 12 months.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

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Ukoniq Lymphoma Drug Safety Investigation Started In February 2022 to Examine Increased Risk of Death

FDA Oncologic Drugs Advisory Committee Meeting in Near Future May Consider Possible Ukoniq Drug Recall

 

(Posted by Tom Lamb at Drug Injury Watch)

 

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UPDATE:  Ukoniq Drug Recall in April 2022 Comes Soon After FDA Warning About Increased Risk of Death in February 2022

(4/18/2022)

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We learned in early February 2022 about an FDA investigation of Ukoniq (umbralisib) after a so-called "safety signal" indicated an association between Ukoniq and increased risk of death in patients treated with Ukoniq for their lymphoma cancer. Ukoniq was approved by the FDA in February 2021 to treat adults with two types of lymphoma:

• Marginal Zone Lymphoma (MZL), when this type of lymphoma cancer has returned or it did not respond to prior treatment with at least one specific type of medicine; and,
• Follicular Lymphoma (FL), when this type of lymphoma cancer has returned or it did not respond to at least three prior treatments.

For more detailed information about this Ukoniq safety signal, we refer you to this February 3, 2022, Drug Safety Communication, "FDA investigating possible increased risk of death with lymphoma medicine Ukoniq (umbralisib)".

In particular, from that February 2022 Ukoniq FDA Drug Safety Communication we get these two points:

1. We conducted an initial review of data from UNITY, a phase 3, randomized, controlled clinical trial in patients with chronic lymphocytic leukemia (CLL). The trial is evaluating Ukoniq in combination with a monoclonal antibody drug that targets a specific protein called CD20 compared to the control arm in which patients received standard treatment. The results showed a possible increased risk of death in patients receiving the combination of Ukoniq and the monoclonal antibody compared to the control arm.... The UNITY trial was conducted in CLL patients, which is not an approved use but rather a use of this drug that is being studied; however, we believe these findings have implications for its approved uses for MZL and FL.
2. We are continuing to evaluate the results from the clinical trial called UNITY. FDA may also hold a future public meeting to discuss these findings and explore the continued marketing of Ukoniq. We have also suspended enrollment of new patients in other ongoing clinical trials of Ukoniq while we continue to review the UNITY findings. We will communicate our final conclusions and recommendations when we have completed our review or have more information to share.

As seen in that second point, there may be an FDA Advisory Committee meeting to consider a possible Ukoniq drug recall in the near future.

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For more on this aspect of the new FDA investigation of Ukoniq, we turn to an article, "FDA Concerned About Safety of Lymphoma Drug", by medical reporter Charles Bankhead, which was published on February 3, 2022, by MedPage Today:

The potential adverse safety signal arose from the phase III UNITY-CLL trial comparing [Ukoniq (umbralisib)] plus the anti-CD20 antibody ublituximab versus obinutuzumab (Gazyva) plus chlorambucil for chronic lymphocytic leukemia [(CLL)]. [Ukoniq (umbralisib)] currently has approved indications for relapsed/refractory marginal zone lymphoma [(MZL)] and follicular lymphoma [(FL)]....

The FDA Oncologic Drugs Advisory Committee (ODAC) may also convene to consider the findings of the safety evaluation and "explore" the continued marketing of [Ukoniq (umbralisib)]....

Late last year, [Ukoniq (umbralisib)] sponsor TG Therapeutics issued a statement acknowledging that the FDA plans to convene ODAC to consider the UNITY-CLL data within the context of the ongoing review of the company's application for approval of the [Ukoniq (umbralisib)]/ublituximab(U2) combination....

Although ODAC has yet to announce a date for the [Ukoniq (umbralisib)] review, the FDA indicated that the meeting would occur in March or April, according to TG Therapeutics.

We will continue to monitor this Ukoniq safety signal and watch for any related FDA regulatory action, including a possible Ukoniq drug recall in the future. Any significant developments related to this new drug safety issue of Ukoniq and increased risk of death will be reported promptly here on Drug Injury Watch.

DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review is done by attorney Tom Lamb)