Limbrel

Overall Position

Our first priority is the health and safety of our patients. Each product contains food-based, highly purified ingredients specially formulated to meet recognized distinctive nutritional requirements of patients with particular medical needs who are managed by active and ongoing supervision by a physician. To ensure safety and effectiveness, each product (or its ingredients) are supported by extensive scientific and clinical testing published in peer-reviewed journals. Our products are dispensed by prescription and cannot be purchased without the direct authorization by a licensed physician, nurse practitioner or physician’s assistant.

Safety Review

On November 8, 2017, the FDA visited Primus asking for copies of Limbrel serious adverse event reports. Primus has investigated and has reported every serious adverse event to the FDA as we learn of them since first marketing our products in 2004. The types of serious adverse events for Limbrel reported to Primus have been consistent over the past 13 years.

On November 21, FDA unexpectedly issued a safety alert stating that the agency had received 194 adverse event reports regarding Limbrel including 57 of the case reports that may have an associative relationship and 30 reports that contain sufficient information to assess a causal relationship. Primus understands these 194 reports cover the entirety of what has been reported so are not limited to their specified concerns and have occurred from the time Limbrel was first introduced in 2004. For perspective on the incidence of occurrence, Primus has sold and sampled approximately 1.7 million units, and Limbrel has been used by an estimated 450,000 patients over this time period.

Primus continues to actively cooperate with FDA and has retained highly respected independent experts to support the review of Limbrel adverse effects and medical literature. These experts have confirmed that the side effects with Limbrel are rare and not potentially life-threatening, and Primus is sharing these expert statements with FDA, while also providing FDA with statements from experts in rheumatology who have extensive clinical experience with Limbrel and who are requesting that, for the benefit of the public health, FDA permits continued marketing of Limbrel.

FDA has required that Primus file, under the Freedom of Information Act, requests to obtain their adverse event reports and health hazard evaluation, showing FDA’s safety rationale, and Primus has filed these requests but has not yet received FDA’s analysis. We cannot, therefore, determine how FDA has reached a different conclusion of Limbrel’s safety, or how FDA has concluded that adverse effects that are shown in the published literature to be not life-threatening are in FDA’s view life-threatening.

Primus will continue to be transparent and work as closely with the FDA as permitted to resolve any food safety or regulatory concerns related to Limbrel.

Additional Information

Limbrel is a prescription medical food for the clinical dietary management of the metabolic processes of osteoarthritis to be used under a physician’s supervision. As a medical food, Limbrel must comply with food-safety standards that are rigorous and different than for drugs.

FDA specifies two serious medical conditions: hypersensitivity pneumonitis and drug-induced liver injury [elevated liver enzymes]. In every case reported to Primus where we have been able to discuss with the patient or physician, these have occurred in new patients trying the product and the adverse reaction to Limbrel resolves without any residual effects when stopping use of the product. These generally occur within the first few weeks of use and are described as individual allergic responses to the product. While these are obviously important and we take them very seriously, Limbrel prescribers, independent experts, and published medical literature all indicate these are not life threatening. Both of these adverse events have been described in Limbrel’s package insert since 2010 and are described in medical information broadly shared with physicians by Primus as well as in published medical literature.

Limbrel has not been recalled though the FDA has asked Primus to make a voluntary recall. Primus is waiting to obtain the documents on which FDA has based its safety alert and recall request prior to making a final decision, although the opinions of independent experts and the medical literature conflict with FDA’s safety alert and request for recall. Primus is open to solutions that will further reduce these rare side effects, such as a patient registry, and we have informed FDA that we want to collaborate with them to assure the best solution for patients and prescribers.