Elmiron Timeline (Pentosan Polysulfate Sodium) Aug. 7, 1985 Elmiron was granted orphan drug status. An orphan drug is one intended to treat a rare disease; usually, it’s the only drug on the market for that disease. The company on the orphan drug designation was the Alza Corporation. 1986 Elmiron was made available on a compassionate […]
Elmiron was granted orphan drug status. An orphan drug is one intended to treat a rare disease; usually, it’s the only drug on the market for that disease. The company on the orphan drug designation was the Alza Corporation.
Elmiron was made available on a compassionate use basis. This means that it could be prescribed to seriously ill patients even though it had not yet been approved.
The trademark for Elmiron was registered with the United States Patent and Trademark Office.
A patent for Elmiron was filed with the United States Patent and Trademark Office.
Baker Cummins Pharmaceuticals Inc. submitted a New Drug Application for Elmiron to the United States Food and Drug Administration (FDA).
FDA sent a letter to Baker Cummins Pharmaceuticals Inc. acknowledging receipt of the New Drug Application for Elmiron.
A mathematical statistician with the FDA, James Gerbert, Ph.D., indicated that the “evidence of of Elmiron for the treatment of interstitial cystitis very weak.”
A review chemist with the FDA, Patricia Stewart, concluded that the New Drug Application for Elmiron was “not approvable from the standpoint of manufacturing and controls.”
James E. Wilson, Ph.D., at the FDA concluded that the application was “approvable from the standpoint of pharmacology with changes in the labeling.”
Daniel Gordin, Ph.D., with the Pharmacokinetics Evaluation Branch of the FDA noted a discrepancy in the chemistry.
Acting Director of the FDA Wiley A. Chambers, M.D., concluded, “the application not recommended for approval.” Chambers recommended that additional information be addressed if the application were to be resubmitted.
Gordin stated that “the bio-data submitted in New Drug Application has not adequately described the bioavailability/pharmacokinetics of and is not adequate to support its approval and its labeling.”
Peter Vaccari at the FDA Office of Orphan Products Development sent a memorandum to FDA Acting Supervisory Consumer Safety Officer Jim Cheever regarding designating Elmiron as an orphan product and requesting to update their information management system to reflect the drug as an orphan product.
Vice President of Regulatory Affairs at Baker Norton Pharmaceuticals Inc. Edward R. Gubish, Ph.D., sent a letter to FDA Director Wiley Chambers advising the FDA that Baker Cummins had undergone an administrative name change to Baker Norton Pharmaceuticals Inc.
Baker Norton amended the New Drug Application.
The FDA acknowledged receipt of the amended New Drug Application dated Dec. 10, 1992.
A patent for Elmiron was granted by the United States Patent and Trademark Office.
The FDA issued a not-approvable letter.
The FDA and Baker Norton Pharmaceuticals Inc. held a meeting to discuss the Jan. 27, 1993, not-approvable letter and requested that Baker Norton Pharmaceuticals study higher doses, specify the primary endpoints, and reanalyze clinical trial data.
FDA Chemist Kermit M. Floyd recommended non-approvability of the application.
Baker Norton amended the New Drug Application.
FDA Acting Division Director Patricia Love, M.D., prepared an internal memorandum to the FDA indicating that some of the responses in the July 7, 1993, amended NDA were adequate but there were still major deficiencies.
At the Pharmacokinetics Evaluation Branch of the FDA, Gordin indicated that the sponsor resubmitted information that was found to be inadequate.
The FDA acknowledged receipt of the amended New Drug Application dated July 7, 1993.
Patricia Stewart, a review chemist with the FDA, concluded that the application was “not approvable from the standpoint of manufacturing and controls.”
Stewart noted that the “application is not approvable as yet and awaiting response to deficiencies.”
Elizabeth A. Turney, M.S., a biomedical statistician with the FDA, concluded that the applicant had failed to provide two independent, adequate, and well-controlled trials to support their claim that Elmiron was effective in the treatment of interstitial cystitis.
A medical reviewer at the FDA, Paul Waymack, M.D., concluded that the sponsor’s comments failed to fully address the request made by the FDA in correspondence dated Jan. 27, 1993.
Dr. Nancy Smith and Dr. Ralph Harkins, medical reviewers at the FDA, sent a memorandum to FDA Acting Division Director Patricia Love, M.D., in which they indicated that the sponsor was unwilling to perform a withdrawal study and an additional well-controlled trial should be required.
An amended New Drug Application was submitted.
Love recommended that the New Drug Application remain not approvable, as there were chemistry and environmental assessment deficiencies that should be added to the non-approval letter.
The FDA acknowledged receipt of the amended New Drug Application dated Feb. 11, 1994.
Paul Waymack, M.D., a medical reviewer at the FDA, indicated that a full report would be required to determine if the study had truly documented safety at the dosages proposed for treating patients with interstitial cystitis.
Review chemist Stewart concluded that “there are still a few chemistry problems that should be resolved before final approval.”
Norman A. See, Ph.D., an FDA reviewing pharmacologist, had a call with a Dr. Kamul Abdul at Baker Norton about the fact that much of the existing data was old. It was agreed that Baker Norton should repeat its studies.
Waymack sent a letter to Love indicating that the number of patients in each trial was insufficient to generate definitive proof of effectiveness.
Baker Norton Vice President Jane Hsiac, Ph.D., sent a letter to Marlene Haffner, M.D., at the FDA regarding outstanding concerns about the effectiveness of Elmiron.
FDA mathematical statistician Nancy D. Smith, Ph.D., recommends that Baker Norton be encouraged to do one large, multicenter study involving none of the investigators who participated in earlier studies.
The FDA issued a second not-approvable letter.
The FDA held a meeting with Baker Norton to discuss the October not-approvable letter.
Waymack indicated that the New Drug Application failed to provide adequate evidence from two well-controlled trials demonstrating that Elmiron was safe and effective in the treatment of the disease and noted that the two studies performed were flawed in that they had multiple investigators in both trials.
Cheever of the FDA spoke with Ed Mitchell of the regulatory affairs department at Baker Norton to request further information regarding existing data.
Love sent a letter to Mitchell regarding discrepancies noted in their meeting.
The New Drug Application was amended.
Stewart indicated that the “application was approvable from a chemistry standpoint.”
The FDA acknowledged receipt of the amended New Drug Application dated Aug. 31, 1995.
FDA Consumer Safety Officer Susan Cusack informed Baker Norton that the chemistry review of the amendment was complete.
Cusack spoke with Steve Viti in the regulatory affairs department at Baker Norton to discuss that the labeling needed further revision.
Cusack spoke with Viti to obtain authorization to discuss Elmiron with another individual.
Stewart concluded that the “application may be approved from a chemistry standpoint.”
Cusack spoke with Viti to ask questions about the Compassionate Use Study.
The New Drug Application was amended.
David J. Lee, Ph.D., a medical reviewer with the FDA, recommended that they not approve Elmiron from a biopharmaceutical perspective, as the bio-data submitted was not adequate to support its approval as well as support its labeling.
Cusack spoke with Viti regarding a request for additional information.
Stewart indicated that the amendment dated Dec. 10, 1995, did not specifically answer each question but the sponsor did present sufficient information to respond satisfactorily to the deficiencies.
Love submitted an internal memorandum to the FDA indicating that Baker Norton had submitted sufficient safety and effectiveness data for Elmiron to be approvable.
An Adverse Events Study looked at incidents associated with Elmiron.
Elmiron was finally approved by the FDA. Baker Norton was the sponsoring company on the FDA approval letter. Baker Norton was a subsidiary of the Ivax Corporation.
FDA statistician Ruthanna C. Davi showed adverse events being reported by Elmiron patients, including nervous system problems in 3.57% of females.
FDA acknowledged receipt of an amended New Drug Application dated April 10, 1996.
Lee and FDA Deputy Director John Hunt commented that the amendment on April 10, 1996, did not adequately address the deficiencies previously indicated for Elmiron. The application was not acceptable from a clinical pharmacology/biopharmaceutical perspective.
The FDA determined that pediatric studies were not needed for Elmiron.
Division Director Brief Comment mentioned that the sponsor was asked to revise the labeling and submit additional safety data.
The FDA approved the application for Elmiron and requested final printed labeling.
Alza acquired the rights to Elmiron from Baker Norton.
Johnson & Johnson issued a news release that Johnson & Johnson was to merge with the Alza Corporation.
Johnson & Johnson acquired the Alza Corporation.
An FDA letter to the Alza Corporation approved a New Drug Application for the removal of the cotton filler used to package Elmiron capsules.
Elmiron’s orphan drug exclusivity expired.
The FDA approved a package insert change.
Teva issued a news release announcing that they had completed acquisition of Ivax.
Ivax and Teva merged.
The FDA approved a product labeling change.
The FDA approved a product labeling change.
The FDA approved a product labeling change.
The Elmiron patents expired. However, no generic was ever marketed in the United States.
Orphan designation was granted by the European Commission to Dr. Ulrich Granzer in Germany for Elmiron for the treatment of interstitial cystitis.
Elmiron was withdrawn in Europe from the list of designated orphan medicinal products on request of the sponsor.
The European Medicines Agency recommended an update for Elmiron to warn about the risk of pigmentary maculopathy, particularly in patients taking Elmiron long-term.
Janssen Pharmaceuticals makes a dramatic change to the Elmiron patient labeling on units sold within the United States. The newly revised patient label, approved by the FDA on June 16, 2020, now warns of “retinal pigmentary changes.” Retinal pigmentary changes could lead to severe and permanent eye injuries such as full or partial blindness, difficulty in adjusting to light changes, and difficulty reading. These eye problems do not improve should the patient discontinue taking Elmiron.
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