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.

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Beovu Drug Label Change in December 2021 Adds More Information About Vision Loss Side Effects

Provides "risk factors and possible mechanism" for Beovu-related Retinal Vasculitis and Retinal Vascular Occlusion

 

(Posted by Tom Lamb at Drug Injury Watch)

 

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

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.... 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....

(3/2/2022)

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We have finally seen the first Beovu drug label change which had been anticipated since Novartis said in May 2021 that the company "will pursue an update to the Beovu prescribing information globally."  As previewed in a Novartis November 2021 "Dear Doctor" letter about Beovu and announced in an MHRA January 2022 Drug Safety Update item for Beovu, there is a revised Beovu Product Information document ("Date of revision of the text: 08 December 2021").  This Beovu drug label change reflects additional information about Beovu vision loss side effects such as intraocular inflammation, including retinal vasculitis and retinal vascular occlusion. We point out, however, that as of this time a similar Beovu drug label change has not been issued by Novartis in the US, yet.

From this Drug Safety Update, "Brolucizumab (Beovu▼): risk of intraocular inflammation and retinal vascular occlusion increased with short dosing intervals", issued January 18, 2022, by the UK's Medicines and Healthcare products Regulatory Agency (MHRA), we get the following:

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.

Here are some details about the "risk factors" for those Beovu vision loss side effects from the so-called "Dear Doctor" letter about Beovu that Novartis UK sent on November 2, 2021, to healthcare professionals in the UK:

Risk factors identified

Novartis conducted non‐interventional retrospective real‐world evidence studies in patients with neovascular (wet) age‐related macular degeneration (nAMD) to better understand the incidence of adverse events/safety signal after initiating treatment with [Beovu (brolucizumab)] for up to 6 months. Each of the two studies consisted of retrospective analysis of large United States real‐world databases, the IRIS Registry® [Study HEORUSV201342] and Komodo Healthcare Map™ [Study HEORUSV201368], respectively. Both assessments were conducted in parallel and were nearly identical to the extent the data permitted.

The results of this retrospective analysis in nAMD patients suggest that patients with a medical history of intraocular inflammation and/or retinal vascular occlusion in the year prior to treatment with [Beovu (brolucizumab)] were more likely to present with similar events after [Beovu (brolucizumab)] injection, as compared to nAMD patients with no history of these events.

In addition, a gender difference with a higher risk for IOI (including RV) and/or RO in females has been observed in the two retrospective studies but also in clinical trials. A higher incidence was also observed in Japanese patients.

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And here is some information about the "possible mechanism" for those Beovu vision loss side effects from that same November 2021 Beovu "Dear Doctor" letter:

Immune‐mediated event

Results of the mechanistic study BASICHR0049 based on an analysis of blood samples from five nAMD patients exposed to [Beovu (brolucizumab)] who subsequently developed retinal vasculitis (RV) and/or retinal vascular occlusion (RO), taken together with accumulated data regarding the association of treatment‐emergent immunogenicity and intraocular inflammation (IOI), indicate a causal link between the treatment‐emergent immune reaction against [Beovu (brolucizumab)] and [Beovu-related] “retinal vasculitis and/or retinal vascular occlusion, typically in presence of IOI”.

In this study, blood samples were collected from the five case patients [retinal vasculitis (RV) and/or retinal vascular occlusion(RO)]and from six control patients who had no signs/symptoms of IOI while still receiving [Beovu (brolucizumab)] treatment....

... In the samples from five patients who experienced the RV and/or RO adverse events a humoral and cellular immune response against [Beovu (brolucizumab)] was identified 3‐5 months after the last [Beovu (brolucizumab)] dose and occurrence of the event. Data showed the presence of high titre ADAs, with a polyclonal and diverse IgG‐driven response against multiple B cell epitopes on the [Beovu (brolucizumab)] molecule, as well as memory T cell activation induced by unstressed and heat‐ or mechanically‐stressed [Beovu (brolucizumab)] preparations.

In the samples from patients from the control group, ADAs, when present, had lower titres.

We expect that a similar Beovu drug label change, and a possible associated Beovu "Dear Doctor" letter, will be issued by Novartis here in the US soon.

Be assured we will continue to monitor the drug safety regulatory sector for further developments regarding Beovu vision loss side effects such as intraocular inflammation, retinal vasculitis, and retinal vascular occlusion.

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

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Elmiron-associated Retinopathy Risks Increased by (1) Longer Duration Use and (2) Higher Cumulative Dosage

Elmiron Lawsuits Filed Because Drug Company Failed to Warn Before June 2020 About Elmiron-related Vision Loss Side Effects

 

(Posted by Tom Lamb at Drug Injury Watch)

 

We are handling Elmiron lawsuits for patients who have developed Elmiron-associated retinopathy, retinal pigmentary changes, or pigmentary maculopathy due to their past use of Elmiron. These Elmiron lawsuits are filed against the drug companies responsible for Elmiron. This is because — despite a growing number of Elmiron-related vision loss case reports in the medical literature over the years — it was not until June 2020 that any warning about these eye problem side effects was included in the Elmiron drug label here in the US.

Both before and after that Elmiron label change in June 2020, there have been various medical studies about the association between Elmiron and serious eye problems such as retinal pigmentary changes or pigmentary maculopathy. We have written several earlier Drug Injury Watch posts, starting back in 2020, covering some of the medical journal articles reporting on those Elmiron side effects studies.

In this post, we draw your attention to the latest such Elmiron study report article, "Pentosan Polysulfate Sodium-Associated Pigmentary Retinopathy: Risk Factors and Fundus Findings", which was published just days ago (December 24, 2021) by the Clinical Ophthalmology medical journal.

From the Abstract we get a summary of this December 2021 medical journal article about Elmiron:

• Purpose: To evaluate the risk factors and fundus findings of patients with potential [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy.
• Patients and Methods: A retrospective chart review was performed of patients exposed to [Pentosan Polysulfate Sodium / Elmiron] who had a dilated fundus examination at a large retina-only practice from 2018– 21. Multimodal images were evaluated by masked reviewers.
• Results: A total of 148 patients were included, of whom 33 (22%) had [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy, and 115 (78%) did not. The mean age was 60.3 years old, and the mean follow-up was 11.8 months. The [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy group had higher mean cumulative doses of [Pentosan Polysulfate Sodium / Elmiron] (1600g± 849 vs 864g± 852, P < 0.0001, Mann–Whitney test) and longer duration of [Pentosan Polysulfate Sodium / Elmiron] use (13.6 years vs 7.48, P < 0.0001). There was no statistically significant difference based on a history of kidney or liver disease or the dosage per day for the weight, body mass index, body surface area, or lean body weight. Of the patients with [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy whose genetic results were available, 15 of 16 (93%) were heterozygous for variants of uncertain significance.
• Conclusion: A longer duration of [Pentosan Polysulfate Sodium / Elmiron] use and higher cumulative dosage of [Pentosan Polysulfate Sodium / Elmiron] were associated with an increased risk of developing [Pentosan Polysulfate Sodium / Elmiron]-associated pigmentary retinopathy. The role of genetic mutations in patients exposed to [Pentosan Polysulfate Sodium / Elmiron] is still to be determined.

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For some important details about Elmiron-associated retinopathy, we point out this excerpt from the Discussion part of that Clinical Ophthalmology medical journal

Some patients with [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy may unfortunately experience difficulty with dark adaptation, reading, contrast sensitivity, and changes in mesopic microperimetry. In the current study, the [Pentosan Polysulfate Sodium / Elmiron]-associated retinopathy group was more likely to have complaints of difficulty with their visual field, reading, dark adaptation, and visual acuity....

There is currently no treatment for [Pentosan Polysulfate Sodium / Elmiron]-associated maculopathy, and the retinopathy can progress even after discontinuing [Pentosan Polysulfate Sodium / Elmiron]. In a multicenter study of 11 patients who had discontinued [Pentosan Polysulfate Sodium / Elmiron], 77% continued to experience progression, with the RPE atrophy growing at a rate of 0.32mm per year, and 9% developing worsening vision over 12 months.... [footnotes omitted]

We are currently investigating possible Elmiron lawsuits for patients diagnosed with Elmiron-associated retinopathy as well as these other serious Elmiron side effects:

• Maculopathy (retinal or pigmentation)
• Retinal Pigmentary Endothelium Injury (RPE)
• Pigmentation Maculitis
• Macular Degeneration (pigmentation or dry)
• Vision Loss / Blindness

It is important to know that our Elmiron lawsuits for patients who have suffered any of these Elmiron side effects are filed only against the pharmaceutical companies responsible for Elmiron — not the doctors who prescribed the Elmiron as a treatment for their bladder diseases.

Significantly, it is not necessary for the patient to have been using Elmiron regularly right up until the time when their Elmiron-related vision loss was diagnosed in order to file an Elmiron lawsuit. That is, unlike most other drug injury cases, the patient could have stopped using Elmiron months before a medical doctor was able to diagnose their eye problem.

For possible Elmiron lawsuits, we encourage you to submit an Elmiron Case Evaluation Form online – it is free, confidential, and there is no obligation. Or, if you prefer, call our toll-free number, (800) 426-9535, to speak directly to attorney Tom Lamb.

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

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Beovu Safety Developments Presented by JAMA Ophthalmology Medical Journal in November 2021

Meanwhile, Still Waiting for the Anticipated Beovu Label Change That Was Previewed by Novartis Back in May 2021

 

(Posted by Tom Lamb at Drug Injury Watch)

 

As the year 2021 draws to an end, we point out some Beovu safety developments which were presented last month by the JAMA Ophthalmology medical journal. We have been tracking Beovu safety issues since February 2020, when we posted this article, "Beovu Side Effects Include Retinal Vasculitis, Eye Inflammation: Safety Issues For Macular Degeneration Drug".

We begin our latest article about Beovu safety issues with this Original Investigation item published November 24, 2021, by the medical journal JAMA Ophthalmology, "Safety Outcomes of Brolucizumab in Neovascular Age-Related Macular Degeneration".

From the Abstract for this November 2021 JAMA Ophthalmology article, we point out these selected parts:

• Importance:  Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu).
• Objective:  To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent [Beovu (brolucizumab)] treatment. Additionally, potential risk factors associated with these adverse events were evaluated.
• Conclusions and Relevance:  The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first [Beovu (brolucizumab)] injection had the highest observed risk rate for IOI and/or RO in the early months after the first [Beovu (brolucizumab)] treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with [Beovu (brolucizumab)] cannot be assessed.

The full text of that JAMA Ophthalmology medical journal article ends as follows:

In conclusion, data from the IRIS Registry and Komodo Healthcare Map provided insights into the safety of patients with neovascular AMD who initiated [Beovu (brolucizumab)]. Patient eyes with IOI and/or RO in the 12 months prior to the first [Beovu (brolucizumab)] injection had the highest estimated incidence rate for an event of any form of IOI and/or RO in the 6 months after first [Beovu (brolucizumab)] treatment. Similar findings were observed among patients with RV and/or RO events. Additional studies with longer follow-up intervals are needed to assess the long-term safety of [Beovu (brolucizumab)] treatment. These results represent early findings that explore potential risk factors for inflammation-associated AEs that may occur following real-world treatment with [Beovu (brolucizumab)]. However, because of study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events and the causality with [Beovu (brolucizumab)] cannot be assessed.

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Next, there is an Invited Commentary piece related to the above medical journal article which was also published November 24, 2021, by the medical journal JAMA Ophthalmology titled "Risk Factors for Intraocular Inflammation After Brolucizumab Treatment", written by Caroline R. Baumal, MD, of the New England Eye Center, at Tufts Medical Center.

Dr. Baumal's JAMA Ophthalmology piece concludes with this statement:

Looking to the future, there are recently completed and ongoing studies evaluating [Beovu (brolucizumab)] (ClinicalTrials.gov, term brolucizumab) to treat retinal disorders that can be combined to provide further information on the incidence, safety, risk factors, and treatment strategies. The patient should be educated about the potential safety issues, therapeutic options, and symptoms of IOI. Clinicians should maintain heightened awareness for RO and/or RV with IOI after [Beovu (brolucizumab)] and be familiar with diagnostic imaging protocols especially widefield fluorescein angiography and recommended treatment algorithms. Based on the current literature, same-day bilateral [Beovu (brolucizumab)] injections should be avoided and [Beovu (brolucizumab)] is contraindicated in eyes with active IOI or a history of IOI related to [Beovu (brolucizumab)]. Based on the study from Khanani and colleagues, a recent history of IOI and/or RO should be considered as another potential risk factor for [Beovu (brolucizumab)]-related IOI.

We will continue to watch for Beovu safety developments which are presented in medical journals or addressed in medical news reports, as well as an anticipated Beovu label change previewed by Novartis back in May 2021 (see: "Beovu Vision Loss Side Effects Continue to Plague Novartis, Ending 3 Key Clinical Trials in May 2021").

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Elmiron and Maculopathy: Increased Risk of Ocular Complications in Long-Term, High-Dose Elmiron Use

Two Recent Medical Articles on Vision Side Effects of Elmiron (pentosan polysulfate sodium, or PPS) for Interstitial Cystitis

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Chronic use of Elmiron (pentosan polysulfate sodium, or PPS) for interstitial cystitis, also known as bladder pain syndrome, has been associated with maculopathy in patients. The mechanism for this link between Elmiron and maculopathy, however, is still not fully understood. And the diagnostic means for identifying a case of Elmiron and maculopathy early on is still evolving. In this post, we look at some relatively recent research regarding the still-emerging drug safety issue of Elmiron and maculopathy.

According to "Screening needed for pentosan polysulfate sodium-associated maculopathy", published on September 2, 2021, by Ocular Surgery News:

In most cases, retinal findings do not appear until a patient has been on [Elmiron] for 10 to 15 years, according to Elliott Sohn, MD, of the University of Iowa. Because patients generally start to present with interstitial cystitis in their 40s, once they start to develop maculopathy, it is easily confused with macular degeneration.

“The maculopathy appears to be dose dependent and most often seen when the patient has been on [Elmiron] for a total cumulative dose of 1,500 g,” Sohn said. “A lot more research needs to be done to better understand why and how this is happening, as well as the prevalence of it.”

Two medical journal articles published in 2021 have presented some of this needed research about Elmiron and maculopathy.

First, from the Abstract for this study report published in the February 11, 2021 edition of the medical journal Clinical Ophthalmology, "Maculopathy Secondary to Pentosan Polysulfate Use: A Single-Center Experience":

• Aim:  To investigate the prevalence of retinal pathology in patients with a history of exposure to [Elmiron (pentosan polysulfate sodium, or PPS)].
• Results:  A total of 131 patients who were exposed to [Elmiron] and seen at the Northwestern Ophthalmology clinic were identified in the EHR. Forty patients of 131 had imaging. Patients with imaging or fundus examination suspicious for [Elmiron] maculopathy were placed into the suspect group. Of the 40 patients that had imaging, 5 (12.5%) had features suspicious for [Elmiron] maculopathy. Of the remaining 91, 5 (5.4%) had macular pigmentary changes described on fundus exam. Among the 10 patients in the suspect group, the average duration of [Elmiron] use was 4.2 years (range 0.3-11.6 years, interquartile range 5.5 years) and the average cumulative dose [of Elmiron] was 380g (range 29-1092g, interquartile range 132g).
• Conclusion:  A novel drug-induced maculopathy has been associated with [Elmiron] use with a distinct clinical constellation that can be accurately identified with multimodal imaging.

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Second, from the Abstract for this study report published in the September 1, 2021 edition of The Journal of Urology, "PD01-09 PATIENT PERCEPTION OF OCULAR RISK IN PENTOSAN POLYSULFATE USE FOR INTERSTITIAL CYSTITIS":

• RESULTS:  A total of 735 patients treated with [Elmiron] were identified, of which 95 completed screening at the Stein Eye Institute. Of the 95, 64 patients consented to the study. Of the 64 patients included in analysis, 37 were no longer taking [Elmiron]. Patients with maculopathy (n=10) were more likely to have discontinued [Elmiron] (n=8) compared to patients without maculopathy (p=0.03). Patients with confirmed ocular complications reported daily doses [of Elmiron] in excess of recommended 300 mg daily dose (590 mg versus 290 mg in those without, p<0.00001) and significantly greater mean lifetime cumulative doses [of Elmiron](671 g versus 3894 g, p=<0.00001). There were no significant differences in age, daily dose, lifetime [Elmiron] dose exposure, or perception of maculopathy risk in those continuing [Elmiron] compared to those who had discontinued [Elmiron]. Primary reasons for discontinuation of [Elmiron] were concern for ocular injury (41%), lack of efficacy or decreased benefit (32%), cost (16%), and other side effects (11%).
• CONCLUSIONS:  While the mechanism of maculopathy in [Elmiron] use is not fully understood, this risk must be weighed against its potential benefit as a treatment for interstitial cystitis. Physicians should counsel patients on risk of ocular complication in long term and high dose [Elmiron] use, and consider alternative therapies and early ophthalmologic referral in patients with lifetime cumulative doses [of Elmiron] greater than 500 g.

Of course, we will continue to monitor this still-emerging drug safety issue of Elmiron and maculopathy.

Our law firm is investigating possible Elmiron drug injury lawsuits for cases of Elmiron causing eye problems such as retinal pigmentary changes and pigmentary maculopathy resulting in vision loss.

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

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Invokana, Farxiga, Jardiance, Other SGLT2 Inhibitors Associated With Retinal Vein Occlusion

Increased Risk for This New Vision/Eyes Side Effect Highest in Elderly Patients and Chronic Kidney Disease Patients

 

(Posted by Tom Lamb at Drug Injury Watch)

 

In June 2021 it was reported that Invokana, Farxiga, and Jardiance, as well as other drugs in the Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors class, are associated with an increased risk of retinal vein occlusion. This new SGLT2 inhibitors side effect was the subject of a presentation at the 81st Scientific Sessions of the American Diabetes Association which was based on the first study to examine the potential association of retinal vein occlusion with the use of SGLT2 inhibitors.

From this news report published on the PracticeUpdate website (free registration required), "ADA 2021: SGLT2 Inhibitors May Increase the Risk of Retinal Vein Occlusion", we get these details:

“SGLT2 inhibitors lower blood glucose levels by increasing urinary glucose excretion and can also reduce body weight and blood pressure,” wrote the authors in their study poster. “Retinal vein occlusion is a peripheral vascular occlusive disease that shares cardiovascular risk factors. As patients with type 2 diabetes have a markedly higher rate of retinal vein occlusion than those without, assessing the risk of retinal vein occlusion associated with the use of new drugs for diabetes is important.”....

In a subgroup analysis, significant interactions were evident with use SGLT2 inhibitors and risk of retinal vein occlusion concerning age ≥ 60 years (hazard ratio 1.53, 95% confidence interval 1.20–1.94, P =.0135) and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (hazard ratio 3.13, 95% confidence interval 155–6.32, P = .0083). No significant interactions were evident for sex, age, body mass index, presence of comorbidities, multiple lifestyle factors, or use of other anti-diabetes agents.

“In a matched cohort study, we found that SGLT2 inhibitors were associated with a significantly increased risk of retinal vein occlusion. The elderly and patients with chronic kidney disease were at higher risk for retinal vein occlusion,” concluded the researchers in the poster.

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Of course, we will continue to monitor the medical literature for more about this new SGLT2 inhibitors side effect related to vision/eyes, retinal vein occlusion.

Previously, Invokana, Farxiga, and Jardiance -- as well as Invokamet, Xigduo, Glyxambi, Synjardy, Qtern, Steglatro, Steglujan, Segluromet, and other SGLT2 inhibitors -- have been associated with other side effects, or adverse drug reactions, such as Fournier’s gangrene and necrotizing fasciitis of the perineum. We have been investigating possible drug injury lawsuits against the responsible pharmaceutical companies for patients who were diagnosed with those serious side effects.

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

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Beovu Vision Loss Side Effects Continue to Plague Novartis, Ending 3 Key Clinical Trials in May 2021

And Novartis "has yet to identify the root cause behind Beovu’s safety problem", According to a News Report

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Starting back in February 2020, when the American Society of Retinal Specialists (ASRS) issued a note to members about 14 cases of retinal vasculitis, Beovu vision loss side effects have handed Novartis setbacks in its efforts to capture market share from Eylea. And in late May 2021, the latest development concerning Beovu safety issues has resulted in Novartis ending three key clinical trials, MERLIN, RAPTOR, and RAVEN.

To begin our coverage of what happened with these three terminated Beovu clinical trials, we turn to this June 1, 2021, FiercePharma news report, "Novartis calls off 3 Beovu trials testing more frequent dosing on concerns of vision-threatening side effect":

The Merlin trial, as well as the Raptor and Raven studies, were testing Beovu given every four weeks. The drug currently carries an FDA label for dosing every eight to 12 weeks after three initial monthly loading doses....

Novartis launched the Merlin trial to see if the more frequent dosing could help age-related macular degeneration patients who still have unresolved retinal fluid despite anti-VEGF therapy. On the efficacy front, 6 mg monthly Beovu matched up to 2 mg monthly Eylea in change in visual acuity after one year of treatment. The drug also bested Eylea on some anatomical secondary endpoints, Novartis said.

But Beovu doubled the rate of intraocular inflammation compared with [Eylea], with 9.3% percent of patients suffering the complication in the Beovu trial arm. That compared with 4.5% for Eylea. None of the Eylea patients developed reginal vasculitis or retinal vascular occlusion, while those side effects happened in 0.8% and 2% of Beovu patients, respectively. The problem could potentially damage a person’s vision.

In Merlin, the rate of vision loss from any cause was 4.8% for Beovu patients and 1.7% for Eylea patients....

The company has yet to identify the root cause behind Beovu’s safety problem.

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You can learn more about these three terminated Beovu clinical trials, MERLIN, RAPTOR, and RAVEN, by looking at their respective pages over at the CliniclTrials.gov website (accessed June 1, 2021):

• Study of safety and efficacy of brolucizumab 6 mg dosed every 4 weeks compared to aflibercept 2 mg dosed every 4 weeks in patients with retinal fluid despite frequent anti-VEGF injections (MERLIN).
• Assessing the efficacy and safety of brolucizumab versus aflibercept in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (RAPTOR). 
• Assessing the efficacy and safety of brolucizumab versus aflibercept in patients with visual impairment due to macular edema secondary to central retinal vein occlusion (RAVEN). 

For a concise characterization of this latest Beovu vision loss side effects development, here is the beginning of a June 1, 2021 article by Endpoints News Senior Editor Amber Tong:

Safety concerns have forced Novartis to slam the brakes on a trio of late-stage clinical studies for its eye drug Beovu, marring grand ambitions to challenge the throne currently occupied by Regeneron’s Eylea.

If one is interested in how Novartis is seeking to present the current status of its lingering Beovu safety issues, this is their May 28, 2021, Media Release item: "Novartis reports one year results of Phase III MERLIN study evaluating Beovu® every four week dosing and provides update on Beovu clinical program". Significantly, it includes this statement:

Novartis has proactively communicated these data to health authorities and will pursue an update to the Beovu prescribing information globally.

We are watching for this forecasted Beovu label change which will, presumably, add new and updated warnings about Beovu vision loss side effects.

In the meanwhile, for background, we point out our June 17, 2020 article, "Beovu Label Change: Warnings About Possible Permanent Vision-Loss Side Effects Added In June 2020".

On a different front, we continue to investigate drug injury lawsuits against Novartis for Beovu when causing vision loss and blindness due to occlusive retinal vasculitis, retinal artery occlusion, and intraocular inflammation. As we have reported previously, starting in January 2021, Beovu lawsuits have been filed for patients alleging Novartis failed to warn doctors and patients about these Beovu vision loss side effects.

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

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Elmiron Drug Safety-related Labeling Changes for Pigmentary Maculopathy Side Effect

March 2021: New Elmiron Medication Guide for Patients Points Out Retinal Pigmentary Eye Problems

 

(Posted by Tom Lamb at Drug Injury Watch)

 

By means of a March 12, 2021, Supplemental Approval letter for Elmiron (pentosan polysulfate sodium) capsules, the FDA announced that certain patient labeling information about Elmiron was being converted to a new Elmiron Medication Guide. In particular, as regards the pigmentary maculopathy Elmiron side effect, this Medication Guide includes the following:

Changes in the retina of the eye (pigmentary maculopathy). Taking ELMIRON may be associated with pigment changes in the retina of the eye that may continue even after stopping treatment with ELMIRON. Tell your healthcare provider including your eye doctor right away if you have any vision changes including any of these symptoms:

• difficulty reading
• your vision takes longer to adjust to low
  or reduced light
• blurred vision

Throughout your treatment, regular eye examinations that include retinal examinations are suggested for early detection of retinal/macular changes....

This Elmiron Medication Guide mandated by the FDA Center for Drug Evaluation and Research (CDER) follows and reiterates the June 2020 Elmiron label change that added a new Warnings subsection, Retinal Pigmentary Changes, which starts with the following information:

Pigmentary changes in the retina, reported in the literature as pigmentary maculopathy, have been identified with long-term use of ELMIRON® (see ADVERSE REACTIONS). Although most of these cases occurred after 3 years of use or longer, cases have been seen with a shorter duration of use. While the etiology is unclear, cumulative dose appears to be a risk factor....

As background, before the June 2020 Elmiron label change adding this new warning about the pigmentary maculopathy Elmiron side effect, the Elmiron drug label had stated "Warnings: None".

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In February 2021 we posted an article, "Past Elmiron Use Linked to Pigmentary Maculopathy and Vision Loss, Again, by Two Recent Medical Studies", in which we reported:

Two new medical journal articles provide further support for the fact that past Elmiron use is associated with pigmentary maculopathy and vision loss. Remarkably, according to one medical study, patients with high levels of Elmiron use have more than a 2-times increased risk for getting a diagnosis of pigmentary maculopathy or macular degeneration.

As we have stated previously, the June 2020 Elmiron label change that finally added warnings concerning vision problems such as retinal pigmentary changes and pigmentary maculopathy was overdue from our perspective. Accordingly, there have been Elmiron lawsuits filed by patients who have suffered vision loss against the pharmaceutical companies responsible for Elmiron.

We are currently investigating possible Elmiron lawsuits for patients with past Elmiron use diagnosed with eye problems such as:

• Vision Loss / Blindness
• Maculopathy (retinal or pigmentation)
• Retinal Pigmentary Endothelium Injury (RPE)
• Pigmentation Maculitis
• Macular Degeneration (pigmentation or dry)

If we can be of assistance to you or someone you know with Elmiron-related eye damage, you can send an email to Tom Lamb or you can call us on our toll-free number: 800-426-9535. Or, if you prefer, simply submit an online Elmiron Case Evaluation Form -- it is free, confidential, and there is no obligation.

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)

Beovu Vision Loss Lawsuits Involve Serious Eye Problems Due to Beovu Injections Reactions

People Need to Know Beovu Lawsuits Are Filed as Individual Cases; No Beovu Class Actions for Beovu Eye Problems

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Starting in January 2021 Beovu lawsuits have been filed for patients alleging Novartis failed to warn doctors and patients about Beovu eye injection reactions which can lead to severe vision loss and blindness. It is important for people to know that these Beovu vision loss lawsuits are filed as individual cases and that there will not be any Beovu class actions for people who have experienced Beovu eye problems. Due to this situation, if a patient has vision loss or blindness after getting Beovu injections in their eyes, this person must contact a lawyer or law firm to handle their Beovu case in order to get legal compensation for the Beovu drug injury they have suffered.

Here are a few reasons why a person with a possible Beovu vision loss lawsuit might want to contact our law firm about handling their Beovu case for legal compensation.

First, we started investigating these Beovu eye problems soon after the American Society of Retinal Specialists (ASRS) issued a Beovu drug safety alert to its members in February 2020.  Therein the ASRS reported 14 cases of retinal vasculitis among patients who had Beovu injections administered in the several months after Beovu first became available in October 2019.

In fact, our February 27, 2020 article, "Beovu Side Effects Include Retinal Vasculitis, Eye Inflammation: Safety Issues For Macular Degeneration Drug", was one of the first articles written about these Beovu eye problems.

Second, since then we have closely monitored this Beovu drug safety issue and written many more articles about the circumstances surrounding case reports of loss and blindness following Beovu injections.  Generally, those patients were diagnosed with one or more of these eye problems:

• Retinal Vasculitis
• Occlusive Retinal Vasculitis
• Retinal Artery Occlusion
• Retinal Vascular Occlusion

To learn more about these serious eye problems following Beovu injections you can look at the Beovu Side Effects page and the Beovu Timeline page over at our DrugInjuryLaw.com website.

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Third, the first three Beovu vision loss lawsuits filed in the US are for clients of our law firm. Each of those three women had their Beovu lawsuit filed as an individual case, which is indicated by this information for those Beovu lawsuits:

1. Harris v. Novartis Pharmaceuticals Corporation, et al.
2. Cohen v. Novartis Pharmaceuticals Corporation, et al.
3. Sundell v. Novartis Pharmaceuticals Corporation, et al.

The basic liability allegations in those Beovu lawsuits, as well as other Beovu cases concerning Beovu eye problems, are:

• Novartis misrepresented that Beovu was a safe treatment for age-related macular degeneration; and,
• Novartis failed to warn about Beovu eye injection reactions causing vision loss and blindness.

Again, we point out these Beovu vision loss lawsuits are filed as individual cases and that there will be no Beovu class actions for Beovu eye problems. As such, people with Beovu eye injection reactions must contact a lawyer or law firm to have an individual Beovu lawsuit filed so they can get legal compensation from Novartis for their Beovu drug injury.

If we can be of assistance to you or someone else regarding a possible Beovu lawsuit for vision loss or blindness due to Beovu eye injection reactions, you can send an email to Tom Lamb or you can call us on our toll-free number: 800-426-9535.

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)

Past Elmiron Use Linked to Pigmentary Maculopathy and Vision Loss, Again, by Two Recent Medical Studies

Patients with High Levels of Elmiron Use Have More Than a 2-Times Increased Risk of Developing Serious Eye Problems

 

(Posted by Tom Lamb at Drug Injury Watch)

 

Two new medical journal articles provide further support for the fact that past Elmiron use is associated with pigmentary maculopathy and vision loss. Remarkably, according to one medical study, patients with high levels of Elmiron use have more than a 2-times increased risk for getting a diagnosis of pigmentary maculopathy or macular degeneration.

Elmiron (pentosan polysulfate sodium, or PPS) was approved by the FDA way back in September 1996 for the treatment of painful bladder syndrome (interstitial cystitis). In recent years, however, cases of Elmiron-related eye damage have been reported.

It is important to know that a patient does not have to have been using Elmiron regularly right up until the time when their pigmentary maculopathy or macular degeneration was diagnosed in order for those conditions to be considered Elmiron-related eye damage.

The first article, "Pentosan Polysulfate and Vision: Findings from an International Survey of Exposed Individuals", was published in December 2020 by the Retina medical journal. From the Abstract for this article:

• Purpose: To investigate patient-reported visual function in individuals taking [Elmiron (pentosan polysulfate sodium, or PPS)] for interstitial cystitis.
• Results: ... Respondents in the highest [Elmiron (pentosan polysulfate sodium, or PPS)] exposure tertile were more likely to report difficulty with reading small print (adjusted OR 2.29, 95%CI 1.15-4.57) and to have a diagnosis of macular degeneration and/or pigmentary maculopathy (adjusted OR 2.41, 95%CI 1.44-4.03) than unexposed respondents.

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The second article, "Maculopathy Secondary to Pentosan Polysulfate Use: A Single-Center Experience", was published in February 2021 by the Clinical Ophthalmology medical journal. From the Abstract for this article:

• Aim: To investigate the prevalence of retinal pathology in patients with a history of exposure to [Elmiron (pentosan polysulfate sodium, or PPS)].
• Methods: Patients exposed to [Elmiron (pentosan polysulfate sodium, or PPS)] and seen in the ophthalmology clinic at Northwestern University during 1/1/2002 to 1/1/2019 were identified from electronic health records (EHR) by an electronic data warehouse (EDW) search. Visual acuity (VA), reasons for clinic visit, ocular conditions, and duration of exposure to [Elmiron (pentosan polysulfate sodium, or PPS)] were noted....
• Results: A total of 131 patients who were exposed to [Elmiron (pentosan polysulfate sodium, or PPS)] and seen at the Northwestern Ophthalmology clinic were identified in the EHR. Forty patients of 131 had imaging. Patients with imaging or fundus examination suspicious for [Elmiron (pentosan polysulfate sodium, or PPS)] maculopathy were placed into the suspect group. Of the 40 patients that had imaging, 5 (12.5%) had features suspicious for PPS maculopathy. Of the remaining 91, 5 (5.4%) had macular pigmentary changes described on fundus exam. Among the 10 patients in the suspect group, the average duration of [Elmiron (pentosan polysulfate sodium, or PPS)] use was 4.2 years... and the average cumulative dose was 380g....

We are currently investigating possible Elmiron lawsuits for patients with past Elmiron use diagnosed with eye problems such as:

Vision Loss / Blindness
Maculopathy (retinal or pigmentation)
Retinal Pigmentary Endothelium Injury (RPE)
Pigmentation Maculitis
Macular Degeneration (pigmentation or dry)

If we can be of assistance to you or someone you know with Elmiron-related eye damage, you can send an email to Tom Lamb or you can call us on our toll-free number: 800-426-9535. Or, if you prefer, simply submit an online Elmiron Case Evaluation Form -- it is free, confidential, and there is no obligation.

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)