Drug Injury Watch

Syfovre Safety-Benefit Assessment by Europe's Drug Regulator Differs From FDA

EMA’s CHMP Does Not Approve Syfovre for a Second Time, Citing "significant risk of adverse events"

 

(Posted by Tom Lamb at Drug Injury Watch)

 

There seems to be some disagreement about the Syfovre safety-benefit assessment when it comes to the US FDA and its European counterpart, the European Medicines Agency (EMA).

In late June 2024, Europe’s drug regulator, the Committee for Medicinal Products for Human Use (CHMP), did not approve Syfovre for a second time, with Apellis Pharmaceuticals asserting it will continue its efforts to market Syfovre in Europe.

From this Fierce Pharma June 28, 2024 article, "EU's drug regulator again rejects Apellis' eye med....", we get the latest on what is happening with Syfovre in Europe:

For the second time in six months, Europe’s Committee for Medicinal Products for Human Use (CHMP) has given a thumbs down to Apellis’ Syfovre for the treatment of patients with geographic atrophy (GA) caused by age-related macular degeneration.

In a release, Apellis noted that there were “multiple dissenting votes” by CHMP members to the opinion. The company added that it plans to seek a reexamination of the opinion, with a final decision expected in the fourth quarter of this year.

“Although the studies showed that Syfovre slowed the growth of geographic atrophy lesions, this did not lead to clinically meaningful benefits for patients,” the CHMP said. “It was noted that benefits of a treatment should impact patients’ everyday functioning, and this was not demonstrated in the studies.”

“In terms of safety,” the CHMP continued, “regular injections into the eye carry a significant risk of adverse events, including the development of other forms of AMD or inflammation in the eye, that could further worsen vision.”

In January of this year, the CHMP adopted its first negative opinion on Syfovre. The drug was approved by the FDA in February of 2023 and generated $275 million in sales last year despite early reports of inflammation for some users.

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For more detail, we get this information from the updated Syfovre (pegcetacoplan) page on the EMA's website (accessed 6/28/24):

The European Medicines Agency has recommended the refusal of the marketing authorisation for Syfovre, a medicine intended for the treatment of geographic atrophy caused by age-related macular degeneration (AMD)....

The Agency issued its opinion on 27 June 2024....

What were the main reasons for refusing the marketing authorisation?

Although the studies showed that Syfovre slowed the growth of geographic atrophy lesions, this did not lead to clinically meaningful benefits for patients. It was noted that benefits of a treatment should impact patients’ everyday functioning, and this was not demonstrated in the studies. In terms of safety, regular injections into the eye carry a significant risk of adverse events, including the development of other forms of AMD or inflammation in the eye, that could further worsen vision. Therefore, the Agency’s opinion was that a positive balance of benefits and risks of Syfovre in the treatment of geographic atrophy caused by AMD could not be established and it recommended refusing marketing authorisation.

As we have reported previously, Syfovre side effects include occlusive retinal vasculitis, which is a type of eye inflammation that blocks blood flow to the retina resulting in vision loss and potentially causing blindness. There have also been cases of non-occlusive retinal vasculitis and other types of eye inflammation.

We have been monitoring this Syfovre drug safety issue since July 2023 on Drug Injury Watch, and these are the four most recent articles:

• Syfovre Retinal Vaso-occlusive Vasculitis Case Report Involving 78-year Old Woman With Vision Loss (4/24/2024)
  
  
• Syfovre Case Report: Occlusive Retinal Vasculitis Shortly After Patient's First Syfovre Injection (3/6/2024)
  
  
• Syfovre Safety Issues Need More Attention Before This Relatively New Eye Drug Gets Widely Prescribed (12/27/2023)
  
  
• Syfovre Update: New Warnings About Retinal Vasculitis and/or Retinal Vascular Occlusion After Syfovre Injections (12/4/2023)
  
  

We continue to investigate possible Syfovre drug injury lawsuits for patients who developed retinal vasculitis or retinal vascular occlusion with resulting vision loss or blindness after their Syfovre injection. These Syfovre lawsuits would be filed against Apellis Pharmaceuticals, the drug company responsible for Syfovre -- not the patient's eye doctor.

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Ozempic Side Effects: Gallbladder Diseases, Thyroid Cancer, And Suicidal Thoughts

Diabetes and Weight-Loss Drug Ozempic Getting Scrutiny From European Drug Safety Regulator EMA

 

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***See also: Ozempic Severe Gastric Side Effects Include Stomach Paralysis, Gastroparesis, And Intestinal Blockages

---

 

(Posted by Tom Lamb at Drug Injury Watch)

 

The popular diabetes and weight-loss drug Ozempic (semaglutide) has been linked to gallbladder diseases which may require gallbladder removal surgery. Other Ozempic side effects being investigated by the European Medicines Agency (EMA) are thyroid cancer and suicidal thoughts.

Starting with the gallbladder disease Ozempic side effects, we previously posted this Drug Injury Watch article, "Ozempic Gallbladder Injury Case Factors: When was the Ozempic Prescribed and For How Long?", which covered the March 2022 Ozempic label change that added warnings about the risks of gallbladder diseases.

Turning next to the possible association between Ozempic and thyroid cancer, we refer you to a June 22, 2023, Reuters news report, "Novo Nordisk says EMA raised safety signal on drugs including semaglutide", which includes this information:

A thyroid cancer safety signal was raised by the EU's drugs watchdog last month over several Novo Nordisk products including semaglutide, which is used in popular diabetes and obesity medicines Ozempic and Wegovy.

The European Medicines Agency (EMA) raised the safety signal, which is a way to monitor potential adverse events from the use of approved drugs, Novo Nordisk said. Such a signal from the EMA does not mean that the medicine is the cause of any reported adverse events.

"Novo Nordisk is aware of the signal and the request by EMA and will deliver a thorough assessment of all relevant data to elucidate this topic," Lars Otto Andersen-Lange, media relations director at Novo Nordisk, told Reuters....

Both EMA and its U.S. equivalent, the FDA, mention on Wegovy's label that semaglutide causes thyroid tumours in rodents but say the effects on humans are unknown. The FDA advises against taking Wegovy if the patient has a family history of thyroid cancer.

We point out that the current Ozempic Prescribing Information document (Revised: 03/2022) also has a warning about a risk of thyroid C-cell tumors.

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Lastly, we take a look at the more recently announced EMA investigation into Ozempic and suicidal thoughts. We begin with this July 10, 2023, Reuters news report, "E.U. investigates Ozempic and weight-loss drug Saxenda after reports of suicidal thoughts", from which we get the following:

The European Medicines Agency is investigating Novo Nordisk’s diabetes drug Ozempic and weight-loss treatment Saxenda after Iceland’s health regulator flagged three cases of patients thinking about suicide or self-harm....

The EMA’s investigation centers on medicines that contain either semaglutide or liraglutide. Novo’s obesity treatment Wegovy, for which demand has surged in the United States, contains semaglutide.

The review was announced weeks after the regulator raised a thyroid cancer safety signal, a means to monitor potentially adverse effects, on several of Novo’s products containing semaglutide.

Suicidal thoughts are not listed as a side effect in the E.U. product information for either drug.

In the United States, however, prescribing instructions for Wegovy recommend that patients are monitored for suicidal thoughts or behavior.

According to the U.S. Food and Drug Administration Adverse Event Reporting System Public Dashboard, there have been at least 60 reports of suicidal ideation since 2018 from patients on semaglutide or their health care providers.

For additional details we point out "Updated: European regulators investigating 150 reports of self-injury, suicide risk in patients taking Novo Nordisk meds for weight loss", which includes this July 2023 reporting by Endpoints News:

The European Medicines Agency is looking into about 150 reports of “possible cases of self-injury and suicidal thoughts” for weight loss patients who used Novo Nordisk’s semaglutide or liraglutide medicines.

The first three case reports were flagged by member agency Icelandic Medicines Agency, unveiled on Monday. The EMA’s safety committee, the Pharmacovigilance Risk Assessment Committee (PRAC), is now investigating.

“The case reports included two cases of suicidal thoughts, one following the use of Saxenda and one after Ozempic. One additional case reported thoughts of self-injury with Saxenda,” the EMA said via email to Endpoints News, before issuing an updated statement today.

The EMA said its review of Ozempic, Saxenda and Wegovy began on July 3 and has now been extended to include other GLP-1 receptor agonists. This review is expected to conclude in November 2023, the regulator said in a statement.

The EMA updated statement referenced above is "EMA statement on ongoing review of GLP-1 receptor agonists", issued July 11, 2023, and here is its introduction to this latest Ozempic drug safety issue:

EMA’s safety committee, the PRAC, is reviewing data on the risk of suicidal thoughts and thoughts of self-harm with medicines known as GLP-1 receptor agonists, including Ozempic (semaglutide), Saxenda (liraglutide) and Wegovy (semaglutide). These medicines are used for weight loss and for treating type 2 diabetes.

At the present time, our law firm is reviewing Ozempic drug injury cases involving gallbladder diseases that lead to the need for gallbladder removal surgery. If we can be of assistance to you or someone you know, we encourage you to submit a Case Evaluation Form online. Or, if you prefer, call our toll-free number, (800) 426-9535,

As regards the possible Ozempic side effects of thyroid cancer and suicidal thoughts or self-injury, we will continue to monitor the two ongoing EMA investigations discussed in this article for further findings as regards these Ozempic drug safety issues.

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Xalkori Vision Side Effects for Pediatric Patients in Clinical Trials Were Seen at an Alarming Rate, Says EMA

Drug Safety Warning: Xalkori-Related Ocular Toxicity and Severe Visual Loss are Difficult to Detect in Children

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Xalkori (crizotinib) is approved by the FDA for the treatment of:

1. Patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test; and,
2. Pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive.

While reviewing a June 14, 2022, European Pharmaceutical Review (EPR) article about the most recent meeting of EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), we learned of a new drug safety issue involving Xalkori-related vision disorders found in clinical trials for pediatric patients treated with Xalkori.

In relevant part from this EPR article about the EMA’s PRAC June meeting highlights:

Xalkori has been studied in children from six to 18 years of age as a monotherapy for the treatment of relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is ALK positive or patients with unresectable, recurrent, or refractory ALK positive inflammatory myofibroblastic tumour (IMT).

Vision disorders have been reported in 61 percent of paediatric patients treated with [Xalkori (crizotinib)] in clinical trials for these indications.

Vision disorders and ocular toxicity are more challenging to detect in children. Paediatric patients should be monitored for ocular toxicity, including the risk of severe vision loss. They should receive a baseline ophthalmologic examination prior to starting Xalkori with follow-up examinations. Healthcare professionals are advised to inform patients and caregivers of the symptoms and remind them to contact their doctor if any of these symptoms develop. Any visual symptoms should be referred to an eye specialist.

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To date, we have not seen any similar FDA warning about this new drug safety issue involving Xalkori-related vision disorders for children.  We point out there were some revisions made in January 2021 to the "5.5 Severe Visual Loss" part of the WARNINGS AND PRECAUTIONS section in the Xalkori Prescribing Information document, but this pertained to patients generally, not pediatric patients only.

We will continue to monitor the drug regulatory sector as well as the medical literature for further developments concerning ocular toxicity and severe visual loss in children treated with Xalkori.

If you have any relevant information about Xalkori-related vision disorders in pediatric patients, please feel free to share by posting a Comment below or, if you prefer, contacting me directly.

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

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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.

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Imbruvica Heart-Related Side Effects Continue to Get Attention from Drug Safety Researchers

Recent Cardiotoxicity Case Reports for Patients Using Imbruvica Alone or When Combined With Other Drugs

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Just about two years ago, in mid-October 2019, we posted these two articles, "Patients Treated With Imbruvica Had Increased Rate Of Fatal Cardiac Events Compared To Conventional Chemotherapy", and "Imbruvica-Related Hypertension And Associated Serious Side Effects Examined In New Medical Study."  Since then, we have seen various case reports of heart-related Imbruvica side effects in the medical literature, both when patients used only Imbruvica and when Imbruvica was used in combination with certain other drugs.

In this new article, we point out a few of the medical journal articles and news reports about heart-related Imbruvica side effects that have been published in the past 12 months.

We start with a June 2021 report from ThePharmaLetter, "Imbruvica: new safety signal for use with rituximab and ACE inhibitors" about the European Medicines Agency (EMA) issuing a new safety signal for Imbruvica with rituximab:

As part of its advice on safety-related aspects to other European Medicines Agency committees, the Pharmacovigilance Risk Assessment Committee (PRAC) last week discussed a direct healthcare professional communication (DHPC) containing important safety information for Imbruvica (ibrutinib).

This DHPC aims to inform healthcare professionals about a new safety signal of sudden or cardiac death with Imbruvica when used in combination with rituximab and angiotensin-converting enzyme (ACE) inhibitors. The signal was recognized following a review of the findings of a clinical trial....

An interim analysis of the clinical trial suggested that the risk of sudden or cardiac death in patients on an ACE inhibitor when entering the study was increased in patients randomized to [Imbruvica (ibrutinib)] and rituximab, compared to those randomized to fludarabine, cyclophosphamide and rituximab.

While the PRAC is reviewing the signal, as a precautionary measure, for patients with [chronic lymphocytic leukemia (CLL)] currently receiving [Imbruvica (ibrutinib)] plus rituximab together with an ACE inhibitor, the PRAC advises healthcare professionals to reconsider the treatment strategy.

Next is a September 2021 MedPage Today news report, "Ibrutinib for CLL Tied to Higher Heart Risks vs Chemotherapy", about there being increased risks for atrial fibrillation, bleeding, and heart failure seen in a Canadian cohort of patients using Imbruvica:

Use of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica) was linked with cardiovascular risks in patients with chronic lymphocytic leukemia (CLL), according to results of a population-based cohort study.

Over 3 years, the incidence of atrial fibrillation (AF)-related healthcare contact was 22.7% in patients treated with [Imbruvica (ibrutinib)] compared with 11.7% in patients who received chemotherapy, risk of hospital-diagnosed bleeding was 8.8% and 3.1%, respectively, and risk of heart failure (HF) was 7.7% and 3.6%, reported Husam Abdel-Qadir, MD, PhD, of Women's College Hospital in Toronto, and colleagues.

There were no significant differences in the risk of ischemic stroke or acute myocardial infarction between the two groups, they noted in the Journal of Clinical Oncology.

For more details about these heart-related Imbruvica side effects, we refer you to the underlying medical study article, "Cardiovascular Risk Associated With Ibrutinib Use in Chronic Lymphocytic Leukemia: A Population-Based Cohort Study", which was published online on August 31, 2021, by the Journal of Clinical Oncology.

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Lastly, there is this November 2020 Healio article, "Link between ibrutinib-related hypertension, heart problems necessitates close monitoring", which provides some key findings from several different medical journal articles about research focused on heart-related Imbruvica side effects. From the Conclusions part of that Healio article:

[Chronic lymphocytic leukemia (CLL)] is a disease of the elderly. Real-world evaluations suggest many patients initiated on [Imbruvica (ibrutinib)] have significant comorbidities, many of them cardiovascular.

Hypertension — an important risk factor for the development of atrial fibrillation — may occur at a much higher rate in real-world practice settings than reported in clinical trials.

Patients should be monitored for the development of new or worsened hypertension, particularly early in the therapy course.

Intervention with antihypertensive medications for patients with hypertension may prevent [major adverse cardiac events (MACE)], including atrial fibrillation. It does not appear that any class of antihypertensives is preferred for hypertension management among these patients.

Treatment of new-onset hypertension, as well as prevention of worsening hypertension and atrial fibrillation development, makes it easier for patients to remain on [Imbruvica (ibrutinib)] without dose modification or interruption.

But if you still want to learn more about this cardiotoxicity drug safety issue for Imbruvica, we give you this "extra" item to consider, "Ibrutinib's Cardiotoxicity-An Opportunity for Postmarketing Regulation", published by JAMA Oncology in February 2021, which starts as follows:

[Imbruvica (ibrutinib)] is an irreversible inhibitor of Bruton tyrosine kinase (BTK) that is indicated for multiple hematological malignancies, including previously untreated chronic lymphocytic leukemia (CLL). This drug is known to have cardiotoxic properties, probably due to off-target inhibition of another kinase. While in randomized trials ibrutinib has been demonstrated to increase survival, some studies have demonstrated fatal toxic effects associated with the drug. This was most obvious in a 3-arm study of CLL in which the 2 [Imbruvica (ibrutinib)] arms were associated with a 7% rate of death during treatment or within 30 days after treatment cessation, compared with a 1% rate of death in the control arm.

We will continue to monitor the medical literature for more analysis of heart-related Imbruvica side effects, as well as watch for possible action by drug safety regulators such as the FDA and the EMA in the future.

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Gilenya Liver Injury Risk Warnings Are Increased, Again, This Time in Canada

Similar Gilenya Drug Label Changes Were Made in Europe and UK During Past Few Months

 

(Posted by Tom Lamb at Drug Injury Watch)

 

On January 18, 2021 Health Canada posted a Gilenya drug safety alert about patients developing Gilenya-associated liver injury, including acute liver failure requiring liver transplant. In the final two months of 2020 we saw similar Gilenya liver risk warnings announced by drug regulators in Europe and the United Kingdom (UK).

This Health Canada Dear Healthcare Professional Letter, "GILENYA (fingolimod) - Risk of Liver Injury", presented this Gilenya drug safety issue as follows:

Post-market cases of clinically significant liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have been reported in multiple sclerosis (MS) patients treated with GILENYA. Some of these cases have resulted in acute liver failure requiring a liver transplant.

Health Canada provided some background, as well as adding new information, in that January 2021 Gilenya drug safety alert:

The most recent periodic review of international safety data identified cases of liver failure, some requiring liver transplant, in patients treated with GILENYA. Other cases of clinically significant liver injury were also reported in patients treated with GILENYA. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have appeared shortly following the initiation of treatment as well as after prolonged use.

During clinical trials, an increase in hepatic enzymes was identified as a very common adverse drug reaction associated with GILENYA. Given the seriousness and severity of recently reported post-market cases, the Canadian Product Monograph (CPM) for GILENYA has been updated to further inform on the risk of liver injury and to include revised guidance for monitoring liver function and criteria for treatment interruption and/or discontinuation.

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We have written about the Gilenya drug label changes with increased liver risk warnings added in Europe and the UK in these previous articles:

• Gilenya Safety Alert November 2020: Cases of Acute Liver Failure Requiring Liver Transplant -- European Medicines Agency (EMA) and Novartis Issue Dear Doctor Letter About Gilenya Label Change
• Gilenya Associated with Cases of Liver Injury, Including Acute Hepatic Failure Requiring Liver Transplant -- January 2021 Drug Safety Update for Gilenya Issued by Medicines and Healthcare products Regulatory Agency

In the US, the Gilenya drug label was revised back in November to add warnings about Gilenya-associated liver injury, including acute liver failure requiring a liver transplant. See 5 WARNINGS AND PRECAUTIONS, 5.5 Liver Injury.

We will watch to see whether the FDA mandates any further Gilenya drug label changes with increased liver risk warnings here in the US going forward.

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How Beovu Went from Potential Blockbuster AMD Drug for Novartis to Possible Beovu Drug Recall in 2021

Key Events for Beovu 2019 - 2020: FDA Approval, Safety Alerts and Warnings, Drug Label Changes, Novartis Investigation

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Leading up to the October 2019 launch of Beovu here in the US, Novartis was hoping its new age-related macular degeneration (AMD) drug would compete with Eylea and Lucentis, which were more established AMD drugs. But then came the unwanted Beovu adverse drug reactions and Beovu-related eye problems, with numerous reports of Beovu causing vision loss and blindness due to occlusive retinal vasculitis, retinal artery occlusion, and intraocular inflammation.

In this article, we walk you through the key events for Beovu in 2019 and 2020 that seem to have moved Beovu away from being a blockbuster AMD drug for Novartis and toward the possibility of there being a Beovu drug recall in 2021.

To start, Beovu was approved by the FDA on October 7, 2019, for the treatment of wet age-related macular degeneration (AMD).

From the outset, this launch of Beovu in the US was a bit rocky for Novartis, as seen by this excerpt from an October 8, 2019, Fierce Pharma piece, "Novartis takes on Regeneron, Roche blockbusters with Beovu approval":

The drug won approval for 8- and 12-week dosing intervals after a three-month loading phase of monthly injections. But SVB Leerink analysts pointed out that the label carries “higher safety liabilities” than Eylea. In the phase 3 trials, patients on Beovu were four times as likely to have intraocular inflammation than those on Eylea, at 4% and 1%, respectively.

Then on February 23, 2020, the American Society of Retinal Specialists (ASRS) issued a note to members about 14 cases of retinal vasculitis across 46,000 injections since Beovu’s launch, as reported by this news report, "Novartis' hot new eye drug Beovu tied to potential vision loss: experts".

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Battling back, a week later Novartis stated the current prescribing information document for Beovu sufficiently addresses its risks of intraocular inflammation and retinal artery occlusion. You can read more about that position in this March 2, 2020, article, "Novartis stands behind Beovu's safety, benefits after vision-loss warning".

About a month later, however, we saw this April 6, 2020,  BioPharmaDive item, "Eye drug side effects are real, Novartis confirms in new warning", reporting Novartis said it would work with the FDA, the European Medicines Agency (EMA), and other drug safety regulators around the world to issue a revised Beovu drug label with new warnings about Beovu-related eye problems.

Next, as announced in this June 9, 2020 Supplemental Approval letter, the FDA approved a label update for Beovu whereby Novartis will add warnings and safety information about retinal vasculitis and retinal vascular occlusion, which can lead to vision loss and blindness.

This was followed a few months later by the September 14, 2020, Novartis Media Release item, "European Medicines Agency (EMA) approves safety label update for Novartis Beovu®".

And lastly, there is this November 14, 2020 Reuters news report, "Novartis identifies possible risk factors for Beovu patients".  Summarily it let us know that, according to a safety review issued by Novartis, the main risk of experiencing Beovu adverse drug reactions such as retinal vasculitis and/or retinal vascular occlusion within the six months after the first administration of Beovu was prior intraocular inflammation and/or vascular occlusion in the year prior to the first injection of Beovu.

We will watch for further developments concerning these various Beovu adverse drug reactions and Beovu-related eye problems, as well as indications of a possible Beovu drug recall in 2021.

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

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Gilenya Safety Alert November 2020: Cases of Acute Liver Failure Requiring Liver Transplant

European Medicines Agency (EMA) and Novartis Issue Dear Doctor Letter About Gilenya Label Change

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

A recent periodic review of Gilenya safety data by the European Medicines Agency (EMA) has turned up cases of Gilenya-related liver failure and drug-induced liver injury associated with Gilenya.  That new Gilenya safety information was presented in this EMA periodic safety update report, "Gilenya (fingolimod): Updated recommendations to minimise the risk of drug-induced liver injury (DILI)", published November 10, 2020.

As regards the cases of Gilenya-related liver failure and drug-induced liver injury associated with Gilenya, from the Direct Healthcare Professional Communication (sometimes called a "Dear Doctor" letter) document included in the November 2020 EMA periodic safety update report for Gilenya we get the following details:

Following the most recent periodic review of safety data, three cases of liver failure requiring liver transplant have been reported in patients treated with [Gilenya (fingolimod)], including one case implying a strong causal relationship with [Gilenya (fingolimod)]. Cases of clinically significant liver injury have also been reported. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, have occurred as early as ten days after the first dose and have also been reported after prolonged use.

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In that November 2020 "Dear Doctor" letter about Gilenya, we get this guidance for physicians treating multiple sclerosis (MS) patients with Gilenya:

Hepatic enzyme increased is a very common adverse drug reaction of [Gilenya (fingolimod)] but due to the seriousness and the severity of recent reported cases, recommendations for discontinuation of the therapy and monitoring have been strengthen and clarify to minimize the risk of DILI. Bilirubin should be checked together with liver transaminase enzymes and liver tests function should be performed regularly until 2 months after [Gilenya (fingolimod)] discontinuation. In case of symptoms suggestive hepatic dysfunction, [Gilenya (fingolimod)] should be discontinued if significant liver injury is confirmed and treatment should not be resumed unless a plausible alternative aetiology for the signs and symptoms of liver injury can be established.

We will continue to monitor the Gilenya safety profile with special attention to cases of Gilenya-related liver failure and drug-induced liver injury associated with Gilenya.

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Picato Recalls Continue with Canada and Denmark Being Most Recent, All Due to Risk of Skin Cancer

A Global Phase-out of Picato Sales by LEO Pharma Inc. Due to this Picato Safety Finding Expected by End of 2020

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

 

But first, we get more information about this latest Picato recall from the above-referenced document:

Health Canada conducted a safety review of PICATO and concluded that there may be a link between its use and an increased risk of non-melanoma skin cancer. On July 2, 2020, Health Canada informed Canadians of this risk. In light of the risk of cancer, Health Canada further assessed the benefit-risk profile of PICATO and determined that the benefits of treatment with PICATO do not outweigh the potential risk of skin cancer.

On October 14, 2020, Health Canada directed LEO Pharma Inc. to stop the sale of PICATO at the manufacturer level. Subsequently, on October 26, 2020, LEO Pharma Inc. initiated the recall of PICATO from the Canadian market.

Here is the July 2020 Picato safety alert issued by Health Canada previously: "Summary Safety Review - Picato (ingenol mebutate) - Assessing the Potential Risk of Skin Cancer".

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Before this Picato recall in Canada, there had been several earlier Picato product withdrawals due to an increased risk of skin cancer as a Picato side effect. As reported in this October 28, 2020 item, "Denmark’s LEO Pharma initiates Picato phase-out", published on thepharmaletter.com site:

Following safety warnings on Picato (ingenol mebutate) from regulators, including the European Medicines Agency and the US Food and Drug Administration, Danish drugmaker LEO Pharma yesterday announced it was initiating a phase-out for the product, a gel for the treatment of actinic keratosis, which is expected to be completed by year-end 2020 at the latest as follows:

In the USA, LEO Pharma provided the FDA with notification of the permanent discontinuation in the manufacture of Picato and the withdrawal of New Drug Application (NDA) 202833 as Picato will no longer be marketed.

In Australia, LEO Pharma has already informed wholesalers and prescribers about discontinuation of Picato and will be withdrawing the marketing authorization.

We will continue to monitor significant developments as regards the Picato safety finding of an increased risk of skin cancer as well as watch for ramifications of the 2020 global Picato recall.

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Safety of Beovu: A Lingering Issue Which Novartis Attempts to Counter with Recent Study Results

Recent Beovu Label Change in Europe Adds Information About Retinal Vasculitis and Retinal Vascular Occlusion

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In mid-September 2020 Novartis announced the results of a Phase 3 head-to-head study comparing its relatively new eye medicine Beovu to Eylea, a more well-established competing eye drug product from Regeneron. According to Novartis, this study shows that after one year of treatment Beovu matched Eylea in terms of the best-corrected vision acuity for patients with diabetic macular edema.

But what has been pointed out as a bit unusual about this recent Beovu study results announcement by Novartis is an emphasis therein on the safety of Beovu. However, this is understandable in view of a February 2020 notification issued by the American Society of Retina Specialists (ASRS) which raised questions about the safety of Beovu.

Novartis had been counting on Beovu to challenge market-leading Eylea, but the ASRS Beovu alert was a set-back for Novartis. The financial consequence of this concern about the safety of Beovu was explained in an August 2020 Reuters news report as follows:  "[Novartis Chief Executive Vas Narasimhan said in an interview that he] believes safety problems that emerged with new eye medicine Beovu have cost Novartis shares 10% of their value."

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Returning to the recent announcement about that Phase 3 study, we get the following from this September 14, 2020 Fierce Pharma article, "Novartis, stressing Beovu safety, matches Eylea in head-to-head diabetic macular edema trial":

Normally, late-stage trial announcements center on a drug’s efficacy, but Novartis singled out Beovu’s safety performance in its statement. Beovu demonstrated a safety profile comparable to Eylea’s, including the rate of intraocular inflammation, the company noted.

Close followers of the rivalry between the two anti-VEGF agents know that inclusion refers to a newly noted Beovu side effect that practically derailed the drug’s initial launch in age-related macular degeneration (AMD).

The intraocular inflammation safety signal led to an update to Beovu’s U.S. and [European Union (EU)] labels, which now include information about retinal vasculitis and retinal vascular occlusion, which can cause blindness. To better understand the problem, Novartis has put together a panel of experts from both within and outside the company to examine its root cause, potential risk factors and mitigation measures.

Here is a Novartis press release about the September 2020 European Beovu label change: "European Medicines Agency (EMA) approves safety label update for Novartis Beovu®".

We reported on the FDA's Beovu regulatory action taken this past summer in this article, "Beovu Label Change: Warnings About Possible Permanent Vision-Loss Side Effects Added In June 2020".

We will continue to watch for news related to the safety of Beovu, and report significant developments here.

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