VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED
January 13, 2005
Mr. Andrew Storey
104 Chancellor Matheson Road
University of Manitoba
Canada R3T 5Y3
Re: BLA STN #103649
WinRho SDF [Rho (D) Immune Globulin Intravenous (Human)]
Dear Mr. Storey:
The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed a Chronic Therapy Message Card (10370-00-ITP-140404, Tab B) for WinRho SDF [Rho (D) Immune Globulin Intravenous (Human)] submitted by your firm under cover of Form FDA 2253. These materials result in the misbranding of WinRho SDF in violation of Sections 502(a), 502(n), and 201(n) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. §§ 352(a), 352(n), and 321(n)) because they make unsubstantiated effectiveness claims representing WinRho SDF to be more effective than has been demonstrated by substantial evidence or substantial clinical experience. Cf. 21 CFR 202.1(e)(6) and (e)(7). These materials could encourage the unsafe use of WinRho SDF in conditions for which FDA has not determined the product to be safe and effective.
According to the FDA-approved professional labeling (PI), WinRho SDF is a plasma-derived gamma globulin (IgG) fraction containing antibodies to the Rho(D) antigen of red blood cells. The PI states that WinRho SDF, "is recommended for the treatment of non-splenectomized, Rho(D) positive:
- children with chronic or acute ITP [immune thrombocytopenic purpura],
- adults with chronic ITP, or
- children and adults with ITP secondary to HIV [human immunodeficiency virus] infection,
in clinical situations requiring an increase in platelet count to prevent excessive hemorrhage." WinRho SDF is also indicated for suppression of Rh Isoimmunization.
The PI also includes detailed risk information including contraindications, warnings, precautions, and adverse reactions. Examples include the following:
- Precaution that, in the treatment of ITP, "patients should be monitored for signs and/or symptoms of intravascular hemolysis (IVH), clinically compromising anemia, and renal insufficiency."
- Adverse Reactions in the treatment of ITP: "The most common adverse events were headache., chills., and fever."
- In Rho(D) positive patients with ITP, "side effects related to the destruction of Rho(D) positive red blood cells [RBC], most notably a decreased hemoglobin, can be expected." "In most cases, RBC destruction is believed to occur in the spleen. However, signs and symptoms consistent with IVH, including back pain, shaking chills, and/or hemoglobinuria, have been reported..." "IVH-related complications that have been reported include death, acute onset or exacerbation of anemia, and acute onset or exacerbation of renal insufficiency."
- General adverse reactions associated with the use of WinRho include, "asthenia, abdominal or back pain, hypotension, pallor, diarrhea, increased LDH, arthralgia, mylalgia, dizziness, hyperkinesea, somnolence, vasodilation pruritus, arash, and sweating."
WinRho SDF is manufactured by Cangene Corporation and distributed by Nabi Biopharmaceuticals.
Unsubstantiated Effectiveness Claim
On the first page of the Chronic Therapy Message Card, with a headline of "Initial Response: WinRho SDF Delivers Excellent Clinical Response Rates in Chronic ITP," there is a comparative table of data showing WinRho SDF clinical response rates of 93%, 88% and 79% for the study of Adult (n=28), Adult (n=24), and Childhood (n=24), respectively. The response rates listed in the PI are 88% and 79%, respectively, for adults and for children.
This table displays data/results from different clinical studies with different study designs, outcomes, and dosages. Your claim of 93% effectiveness is false or misleading because it is derived from data that do not constitute substantial evidence or substantial clinical experience [Cooper, N., et al, Does treatment with intermittent infusions of intravenous anti-D allow a proportion of adults with recently diagnosed [ITP] to avoid splenectomy?, Blood, 15 March 2002, Vol. 99, No. 6, pp. 1922 - 1927]. This study does not constitute substantial evidence or substantial clinical experience for several reasons, including:
- The patient population enrolled was not limited to Chronic ITP patients and the conditions of prior treatment were varied.
- The study examined a different indication for use (avoiding splenectomy) than that for which your product has been approved.
- The source of the data you cited did not collect adverse event data other than assessment for signs of bleeding. Collection of adverse event data is important to fully evaluate the safety of this dose (75 ?g/kg) and product.
If you have other data consisting of substantial evidence or substantial clinical experience to support your claim, please submit the data, within ten (10) days of the date of this letter, to CBER for review. In the absence of such data, you should immediately discontinue any further use of these claims in all advertising and promotional materials.
Conclusion and Requested Actions
The Chronic Therapy Message Card misbrands WinRho SDF within the meaning of sections 502(a), 502(n), and 201(n) of the Act (21 U.S.C. §§ 352(a), 352(n), 321(n)) because it represents WinRho SDF to be more effective than has been demonstrated by substantial evidence or substantial clinical experience.
We request that Cangene Corporation and your distributor (Nabi Biopharmaceuticals) immediately cease the dissemination of violative promotional materials for WinRho SDF such as those described above. Please submit a written response to this letter within ten (10) business days of the date of this letter, stating whether you intend to comply with this request, listing all violative promotional materials for WinRho SDF such as those described above, and explaining your plan for discontinuing use of such materials. Please direct your response to Glenn N. Byrd at the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, HFM-602, 1401 Rockville Pike, Rockville, Maryland 20852-1448. In all future correspondence regarding this matter, please refer to the BLA/STN number. We remind you that only written communications are considered official responses.
The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for WinRho SDF comply with each applicable requirement of the Act and FDA implementing regulations.
----- signature -----
Robert A. Sausville
Acting Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
Lewis Pollack, Ph.D.,
Sr. Director, Regulatory Affairs
12280 Wilkins Avenue
Rockville, MD 20852