FDA draft guidance addresses clinical development of drugs to treat early Lyme disease
APR 2, 2023 —
The FDA is drafting guidance for Lyme Disease Drug Development. Not surprisingly they have completely mischaracterized the disease and target patient population. It looks like we have an important opportunity to educate them before sick patients aren’t included in the cohorts eligible to receive treatment. Similar to the vaccine, working with the wrong population will make treatments look effective even if they are not. It also prevents drug developers from being able to address what the real disease is and does. April 3 at 11:59 pm is the deadline for comments. Please consider commenting and/or sharing with others.
Carl Tuttle’s Submitted comment…
Early Lyme Disease as Manifested by Erythema Migrans: Developing Drugs for Treatment; Guidance for Industry – DRAFT GUIDANCE
Office of Communications,
Division of Drug Information Center for Drug Evaluation and Research
Food and Drug Administration
Focusing on the early stage of Lyme disease with bulls-eye rash is the root cause of this failed Public Health Response. Less than 50% of Lyme patients developed that rash as recorded by Epidemiologists in the State of Maine.
2011, 42% developed the rash: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/vector-borne/lyme/documents/2011-lyme-legislature.pdf
2012, 49% developed the rash: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/vector-borne/lyme/documents/2012-lyme-legislature.pdf
2013, 51% developed the rash: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/vector-borne/lyme/documents/2013-lyme-legislature.pdf
2014, 57% developed the rash: http://www.maine.gov/dhhs/mecdc/infectious-disease/epi/vector-borne/lyme/documents/2014-lyme-legislature.pdf
Lyme was pigeonholed into the category of “Hard to Catch and Easily Treated” through an elaborate scheme focusing on the acute stage of disease with bulls-eye rash and early treatment while avoiding the horribly disabled Lyme patient population. [i] The Centers for Disease Control financed the dishonest science using taxpayer dollars [ii] under grant# RO1 CK 000152 [iii] which has misguided a nation of intelligent physicians through the deliberate suppression of evidence of persistent Borrelia infection after aggressive antibiotic treatment. [iv]
This well-orchestrated scheme has misclassified Lyme as a low-risk and non-urgent health threat which actually belongs in the same health threat category as AIDS, Zika, cancer etc. and requires a Manhattan Project to understand how the infection it disables its victim just like untreated strep throat leads to rheumatic fever causing irreversible heart damage, untreated HIV leads to AIDS with substantial disability and death and untreated syphilis leads to progressive disability and dementia. Patients with a prolonged exposure to the Lyme disease pathogen are almost always incapacitated. Many these patients are often diagnosed with the chronic diseases of our time with no known etiology as exposed in the “Under our Skin” extended trailer:
Under Our Skin – Extended Trailer (please watch)
There are no guidelines for treating the late stage disabled Lyme patient (who ends up bedridden or in a wheelchair) listed in the recently revised IDSA Lyme Treatment Guideline because that class of patient has been deliberately avoided at all costs so as not to expose the truth while keeping the current paradigm intact.
In fact, the IDSA does not want clinicians to rule out Lyme in patients who have been diagnosed with the chronic diseases of our time:
June article in Medscape by past IDSA president Paul Auwaerter
A Quick Tour of the New Lyme Disease Guideline
Paul G. Auwaerter, MD
June 14, 2021
“Of importance, the guideline goes out of its way to cite the lack of evidence for performing Lyme disease tests, specifically routine testing in cases where there’s no evidence or link to Lyme disease. Examples include someone who is asymptomatic after a tick bite, even when they have a neurologic condition such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson’s disease, dementia, or any kind of new-onset seizures or psychiatric illness. In children, behavioral and developmental disorders don’t warrant assessing a Lyme disease serology.”
I sent an email to Dr. Auwaerter pointing out that a recent study identified tick-borne infections in nine out of ten institutionalized adolescents: [v] [vi]
Study detects tick-borne illness in teens hospitalized for depression
-Ten patients were diagnosed with DSM-5 Major Depressive Disorder, seven were additionally diagnosed with Generalized Anxiety Disorder, and three had made serious suicide attempts.
-Ten adolescents picked at random with mental illness severe enough that they required institutionalization— nine of them had evidence of tick-borne infections and nine had evidence of autoimmune encephalitis.
Instead of playing along with the dishonesty by avoiding the truth/evidence that Lyme is a disabling disease, our public health officials responsible for this travesty should be thoroughly investigated and held accountable to ensure this atrocity will never repeat itself.
Stop focusing on the early stage of Lyme disease with bulls-eye rash and find a cure for all stages of the disease. Include patients in this study who are horribly disabled by an infection capable of destroying lives, ending careers while leaving its victims in financial ruin as reported by the Lyme patient population for the past thirty years!
References (please read them!)
- NEWS: Former patient who testified as a child about Lyme disease recalls encounter with Sen. Ted Kennedy
Evan White testified from his wheelchair in 1993 at Senator Ted Kennedy’s Hearing, Washington DC
“No one could hear or feel the moment of that child and not be moved,” Kennedy explained to the [Boston] Globe at the time. Anyone who wasn’t moved, he said, “hasn’t got a heart.”
- Feb 4, 2020 complaint regarding the misuse of taxpayer dollars https://www.change.org/p/the-us-senate-calling-for-a-congressional-investigation-of-the-cdc-idsa-and-aldf/u/25876147
- Subjective Symptoms after Treatment of Lyme Disease https://reporter.nih.gov/search/14E9C8084784C1D47598B8961CAA4A01A2FFCEB861BF/projects?shared=true&legacy=1
- Lyme borreliosis: diagnosis and management https://www.bmj.com/content/369/bmj.m1041/rr-1
- A Quick Tour of the New (IDSA) Lyme Disease Guideline https://www.change.org/p/the-us-senate-calling-for-a-congressional-investigation-of-the-cdc-idsa-and-aldf/u/29231613
- A Quick Tour of the New (IDSA) Lyme Disease Guideline #2 https://www.change.org/p/the-us-senate-calling-for-a-congressional-investigation-of-the-cdc-idsa-and-aldf/u/29263852
FDA draft guidance addresses clinical development of drugs to treat early Lyme disease Part 2
As a follow-up to my previous comment to the FDA regarding “drugs to treat early Lyme disease,” please take a moment to read the comment below registered by the team at TruthCures. We all agree that early Lyme with bulls-eye rash does not represent the entire patient population and has been used by the IDSA and CDC to control and manipulate the narrative in order to support the vaccine business model of patent royalties and pharmaceutical profits. Chronic Lyme disease DOES NOT fit that model!
Comment from TruthCures:
Response to Docket No. FDA-2022-D-2315 for “Early Lyme Disease as Manifested by Erythema Migrans: Developing Drugs for Treatment”
As a patient advocacy organization working to bring valid diagnostics and effective treatments to people with Lyme disease (LD), TruthCures supports innovation in therapeutics and properly designed trials to ascertain their efficacy. Thank you for the opportunity to comment on this guidance.
The trial population suggested in this guidance consists of “…subjects with early localized (i.e., a single EM lesion) or early disseminated (i.e., multiple EM lesions) disease, who reside in or traveled to a Lyme-endemic area.” Limiting any therapeutic trial to only cases presenting with erythema migrans (EM) rash will restrict the trial population to a minority cohort that may not be representative of the broader patient population.
The Centers for Disease Control and Prevention (CDC) estimates 476,000 LD cases in the United States each year (Kugeler et al 2021). However, in 2020, only 44,937 LD cases were reportable as “confirmed” or “probable” based on CDC surveillance criteria (CDC 2020). For diagnosis of a reportable case of early LD, CDC surveillance criteria require either a physician-diagnosed EM rash or laboratory confirmation of infection by methods that may include culture, nucleic acid amplification, immunohistochemical assay on biopsy or autopsy tissues, or two-tier serological testing (CDC 2022).
In clinical practice, diagnostic criteria set forth by the Infectious Diseases Society of America are virtually indistinguishable from the CDC surveillance criteria (IDSA 2006). With both sets of criteria requiring physician-diagnosed EM rash and/or laboratory confirmation, it stands to reason that the vast majority of EM rashes are being counted in the reported surveillance cases. In the public discourse, the absence of such context promotes a misconception that the prevalence of EM rash is based on the total of LD cases rather than the reported cases, creating an inflated perception of the prevalence of EM rash with Lyme.
A simple mathematical analysis illustrates the staggering difference between the narrative and reality.
● The literature frequently cites an EM rate of 60% – 80% (IDSA 2006, Steere et al 1998, CDC 2021). For calculation purposes we will use 70%.
● The public incorrectly believes EM cases are calculated as 70% of 476,000, or 333,200.
● Published studies state the EM rate is calculated based on reported LD cases—those meeting the IDSA and/or CDC surveillance reporting criteria (Kugeler 2020, Smith et al 2002, Seltzer et al 2000). For 2020, EM cases
would be 70% of 44,937, or 31,456.
● Therefore, the effective rate of EM is about 6.6% (31,456 out of 476,000).
It should not have to be said that results of a treatment trial limited to 6.6 percent of patients would not necessarily extrapolate to the entire Lyme disease patient population—particularly when it is unclear why the minority exhibit a distinct cutaneous manifestation. Indeed, Kannangara and Patel note, “EM seems to correlate more with the arthropod than the associated pathogen. The common belief is that EM is caused by B. burgdorferi. The presence of an organism in a skin biopsy culture or PCR does not necessarily mean that it is the cause of EM.” (Kannegara 2020)
From the guidance document:
“Clinical success should be defined as resolution of EM and continued absence of objective manifestations of Lyme disease without need for additional antibacterial treatment for Lyme disease.”
“Clinical failure should be defined as the presence of unresolving or recurrent EM, objective manifestations of Lyme disease, or the need for additional antibacterial treatment for Lyme disease.”
Remission of cutaneous symptoms has not been determined to correlate with disease cure (IDSA 2006, Steere et al 2016, Feder et al 2011), and, as is common knowledge, there is no diagnostic method available to determine either cure or disease stage.
It is commonly reported in the literature that EM rash resolves on its own in three to four weeks (Kardos 2002, Feder 1993, Nadelman 1997, Wheaton 2012, Dressler 1999). Therefore, the definition of clinical success (“resolution of EM”) could not necessarily be attributed to the treatment. Likewise, clinical failure could not be attributed to lack of efficacy if efficacy itself is not ascertainable. Lacking the ability to determine success or failure based on EM resolution, an alternative would be to run a separate trial to determine whether the therapeutic has any effect on time to resolution of EM.
Additionally, there is the possibility that patients present with EM rash and no other symptoms. In these cases, without the ability to correlate disease cure with resolution of EM, there is no other way to gauge efficacy of a therapeutic.
Using only patients who present with EM rash for a therapeutic efficacy trial would exclude 93% of patients, with no insight into the factors (e.g. genetic or comorbidities) that cause certain people to develop the rash. Resolution of EM rash is not an indication that Lyme disease has been cured or spirochetes eradicated.
TruthCures’ mission is to enable Lyme disease victims to obtain a valid diagnosis and effective medical care. While we support endeavors to discover novel treatments, we believe valid diagnostics must come first. As long as Lyme disease cannot be accurately and consistently diagnosed, therapeutics cannot be developed for the right patients using the right efficacy endpoints.
Following a complaint to FDA’s Office of Criminal Investigation, TruthCures presented to investigators in-person, in October 2021. We provided evidence that Lyme disease diagnostics have been predicated on improperly cleared devices going all the way back to 1995. The investigators agreed with our diagnostic device regulatory expert’s assessment of those devices. We suggest focusing FDA’s Lyme disease efforts on completing that investigation so valid tests can be developed and marketed rather than daisy-chaining off a manipulated standard.
It is well known that seronegative Lyme presents one of the biggest challenges in validating diagnostics. The gap between reported surveillance cases (44,937 in 2020) and CDC’s estimated annual cases (476,000) indicates more than 400,000 patients per year may be falling through the cracks due to the inability of serology to properly diagnose them. Many of these victims lose everything—family, friends, job, home, retirement savings, education, and more—due to chronic illness and the stigma of having a “contested” disease. We respectfully request you take a step back and reassess whether it makes sense to produce any guidance that effectively leaves those patients out of the equation once again.
- Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS; Hinckley AF. Estimating the
Frequency of Lyme Disease Diagnoses, United States, 2010-2018. Emerg Infect Dis
- Centers for Disease Control and Prevention. “2020 Lyme Disease Data: Provisional Data.” Centers for Disease Control and Prevention, 2020,https://www.cdc.gov/lyme/datasurveillance/provisional-lyme-cases.htm
- Centers for Disease Control and Prevention. “2022 Lyme Disease Surveillance Case Definition.” Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, 1 Jan. 2022, www.cdc.gov/lyme/resources/2022-surveillance-case-definition.html
- Infectious Diseases Society of America. “The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America.” Clinical Infectious Diseases, vol. 43, no. 9, 1 Nov. 2006, pp. 1089-1134.
- Steere AC, Sikand VK, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. N Engl J Med. 1998;339(4):209-215. doi: 10.1056/nejm199807233390401.
- Centers for Disease Control and Prevention. “Signs and Symptoms of Untreated Lyme Disease.” Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, 2021. https://www.cdc.gov/lyme/signs_symptoms/index.html
- Smith, R. P., Schoen, R. T., Rahn, D. W., Sikand, V. K., Nowakowski, J., Parenti, D. L., …& Steere, A. C. (2002). Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Annals of Internal Medicine, 136(6), 421-428.
- Seltzer, E. G., Gerber, M. A., Cartter, M. L., Freudigman, K., & Shapiro, E. D. (2000). Long-term outcomes of persons with Lyme disease. JAMA, 283(5), 609-616.
- Kannangara, Don Walter and Patel, Pritiben. “Report of Non-Lyme, Erythema Migrans Rashes from New Jersey with a Review of Possible Role of Tick Salivary Toxins.” Journal of Medical Entomology, vol. 57, no. 1, 2020, pp. 28-34.
- Kardos, Marton, et al. “Erythema migrans resolving without antibiotic treatment in a patient with confirmed Lyme disease.” Journal of the American Academy of Dermatology, vol. 47, no. 3, 2002, pp. S204-S207. doi: 10.1067/mjd.2002.123625.
- Feder, Henry M. Jr., et al. “A Critical Appraisal of ‘Chronic Lyme Disease’.” New England Journal of Medicine, vol. 328, no. 7, 1993, pp. 921-924. doi: 10.1056/NEJM199304013281311.
- Nadelman, Robert B., et al. “Does this Patient Have Lyme Disease?” Annals of Internal Medicine, vol. 127, no. 12, 1997, pp. 1109-1113. doi: 10.7326/0003-4819-127-12-199712150-00005.
- Wheaton, Anne J., et al. “Lyme Disease in Primary Care Practice.” Journal of the American Board of Family Medicine, vol. 25, no. 6, 2012, pp. 817-820. doi: 10.3122/jabfm.2012.06.120055.
- Dressler, Franz, et al. “The Clinical Spectrum and Treatment of Early Lyme Borreliosis in Patients with Skin Manifestations Only.” Journal of the American Academy of Dermatology, vol. 41, no. 3 Pt 1, 1999, pp. 1-7. doi: 10.1016/S0190-9622(99)70134-7.
- Steere, A. C., Strle, F., Wormser, G. P., Hu, L. T., Branda, J. A., Hovius, J. W., … & Stanek, G. (2016). Lyme borreliosis. Nature Reviews Disease Primers, 2, 16090.
- Feder, H. M., Johnson, B. J., O’connell, S., Shapiro, E. D., Steere, A. C., Wormser, G.P., & Ad Hoc International Lyme Disease Group. (2007). A critical appraisal of “chronic Lyme disease”. New England Journal of Medicine, 357(14), 1422-1430.