02142020

Rare Disease Highlight: Narcolepsy
by Rare Disease Highlight

Narcolepsy is a rare disease that affects 1 in every 2,000 people worldwide 1. Narcolepsy is characterized by symptoms of excessive daytime sleepiness, hallucinations upon falling asleep and waking up, insomnia, sleep paralysis, and falling quickly into the rapid eye movement (REM) stage upon falling asleep 1,2. Narcolepsy is divided into two subtypes: Narcolepsy type 1 (N1) and type 2 (N2) 1,3. N1 is well understood and is thought to be autoimmune in nature 1,3,4. In addition to classic symptoms of narcolepsy, those with N1 almost always experience cataplexy – a phenomenon where a patient loses muscle control upon experiencing strong emotion. Those with N2 do not typically present with cataplexy, however, these patients can potentially experience cataplexy later in life, and their diagnosis will be changed accordingly 1,3.

Narcolepsy is a lifelong disorder presenting anywhere from childhood to young adulthood, however, an official diagnosis, which is confirmed by a sleep study completed in a sleep lab, may be delayed until adulthood 1,3,5. Misdiagnosis and comorbidities, as well as a lack of effective symptom recognition and awareness, may all lead to the average amount of time between symptom presentation and diagnosis being between 8-22 years 4,6. Treatment for narcolepsy is typically a combination of stimulants, wake-promoting medications, and sleep agents to help with insomnia and fragmented sleep patterns 1. Antidepressants and some sleep medications may also be used to treat cataplexy 1,2. Newer medications are being developed that promote wakefulness through more specific pathways, however, there is still no cure developed 1,2,3. There is also the question of reliability in sleep study results and subsequent diagnosis 5. These medication and diagnostic challenges point to a need for further research and development to create more effective medications and diagnostic tools for those affected by narcolepsy.

References

  1. Bhattarai J, Sumerall S. Current and Future Treatment Options for Narcolepsy: A Review. Sleep Sci. 2017;10(1):19-27.
  2. Burgess CR, Scammell TE. Narcolepsy: neural mechanisms of sleepiness and cataplexy. J Neurosci. 2012;32(36):12305-12311.
  3. Barateau L, Dauvilliers Y. Recent advances in treatment for narcolepsy. Therapeutic Advances in Neurological Disorders. 2019;12:1756286419875622.
  4. Golden EC, Lipford MC. Narcolepsy: Diagnosis and management. Cleveland Clinic Journal of Medicine. 2018;85(12):959.
  5. Lopez R, Doukkali A, Barateau L, et al. Test–Retest Reliability of the Multiple Sleep Latency Test in Central Disorders of Hypersomnolence. Sleep. 2017;40(12).
  6. Morse AM. Narcolepsy in Children and Adults: A Guide to Improved Recognition, Diagnosis and Management. Med Sci (Basel). 2019;7(12).

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

02072020

Rare Disease Highlight: Multiple Myeloma
by Rare Disease Highlight

Multiple Myeloma (MM) is a rare cancer that is characterized by the uncontrolled growth of white blood cells1-4. This uncontrolled growth is caused by changes and mutations to the DNA of the cells5,6. There are different subtypes of MM which are characterized by the number and type of mutations observed, along with prognosis associated with each subtype3,5,7,8. The underlying cause of MM is unknown, however, some individuals are at a higher risk for developing MM, including those who are of older age, male, African American, and those with a family history of MM2,4,9. MM is the second most common blood cancer and makes up about 1% of all cancer diagnoses2,4.  An early, inactive form of MM, called Smoldering Multiple Myeloma (SMM), usually occurs in patients before they are diagnosed with MM4,7,10. The difference between SMM and MM is that those with SMM won’t have visible symptoms, while MM patients will present with anemia, an increase in serum calcium, bone lesions, compromised immune function, kidney issues, and other complications4,10,11. The chances of SMM developing into MM is 10-20% each year7. Current treatments include stem cell transplant, chemotherapies, surgery, radiation, and novel therapies such as immunomodulatory agents and proteasome inhibitors12,13. Around 52.25% of patients diagnosed with MM survive 5 years past diagnosis14. Recent improvements in treatments have brought the survival rate of MM up, however,  there is still no cure, and current treatments are not always successful or have associated complications indicating that there is still a large need for investigations into newer and more effective treatments3,4,6.

References

  1. Kyrtsonis M-C, Koulieris E, Bartzis V, et al. Monoclonal Immunoglobulin. In: Multiple Myeloma – A Quick Reflection on the Fast Progress.2013.
  2. Halvarsson BM, Wihlborg AK, Ali M, et al. Direct evidence for a polygenic etiology in familial multiple myeloma. Blood Adv. 2017;1(10):619-623.
  3. Van Wier S, Braggio E, Baker A, et al. Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma. Haematologica. 2013;98(10):1586-1592.
  4. Smith L, McCourt O, Henrich M, et al. Multiple myeloma and physical activity: a scoping review. BMJ Open. 2015;5(11):e009576.
  5. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23(12):2210-2221.
  6. Chretien ML, Corre J, Lauwers-Cances V, et al. Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter? Blood. 2015;126(25):2713-2719.
  7. Prideaux SM, Conway O’Brien E, Chevassut TJ. The genetic architecture of multiple myeloma. Adv Hematol. 2014;2014:864058.
  8. Kazandjian D, Hill E, Hultcrantz M, et al. Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients. Blood Cancer J. 2019;9(2):15.
  9. Alexander DD, Mink PJ, Adami H-O, et al. Multiple myeloma: A review of the epidemiologic literature. International Journal of Cancer. 2007;120(S12):40-61.
  10. Eslick R, Talaulikar D. Multiple myeloma: from diagnosis to treatment. Aust Fam Physician. 2013;42(10):684-688.
  11. Bladé J, Rosiñol L. Complications of Multiple Myeloma. Hematology/Oncology Clinics of North America. 2007;21(6):1231-1246.
  12. Mikhael J, Ismaila N, Cheung MC, et al. Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline. Journal of Clinical Oncology. 2019;37(14):1228-1263.
  13. Wallington-Beddoe CT, Pitson SM. Novel therapies for multiple myeloma. Aging (Albany NY). 2017;9(8):1857-1858.
  14. National Institute of Health. Cancer Stat Facts Web site. https://seer.cancer.gov/statfacts/html/mulmy.html. Published 2016. Accessed 02/05, 2020.

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

RWE Submissions: FDA Drafts Guidance
by Regulatory News

With an eye toward better tracking the use of real-world data (RWD) to generate real-world evidence (RWE), the US Food and Drug Administration (FDA) on Wednesday drafted guidance to help sponsors provide information to the agency on their use of RWD and RWE in a uniform format.

The uniform format is meant to help the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) track certain types of submissions using RWE under an investigational new drug application (IND), new drug application (NDA) or biologics license application (BLA).

Relevant submissions may include RWE used to support study objectives, such as: “IND submissions for randomized clinical trials that use RWD to capture clinical outcomes or safety data, including pragmatic and large simple trials; New protocols for single arm trials that use RWE as an external control; Observational studies that generate RWE intended to help to support an efficacy supplement; Clinical trials or observational studies using RWE to fulfill a postmarketing requirement to further evaluate safety or effectiveness and support a regulatory decision.”

But FDA also said in the 5-page draft that it does not intend to track RWE submissions that are not tied to a specific product or are not being used to support a regulatory decision regarding safety and/or effectiveness.

Such submissions that do not have to be identified as containing RWE include: “Natural history studies for development of a clinical outcome assessment or biomarker; Feasibility studies using RWE; Studies using RWD to perform exploratory analyses and generate hypotheses.”

In the cover letter accompanying a submission, FDA explains how the sponsor or applicant should identify the submission as containing RWE by including the following information: Purpose of using RWE as part of a regulatory submission (e.g. as part of a new product approval, to provide evidence to support a labeling change or as part of a postmarket commitment); study design using RWE (e.g. randomized or single-arm trial); RWD source(s) used to generate RWE.

Such RWD source(s) can include: “Data derived from EHRs; Medical claims and/or billing data; Product and/or disease registry data; Other data sources that can inform on health status (e.g., data collected from mobile technologies, patient-generated data).”

FDA explained that it will use this information for internal tracking purposes only.

The draft guidance also includes an appendix with a sample presentation of the cover letter for submissions including RWE.

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Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation, operating like a not-for-profit, dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutics areas to help drug developers advance treatments for the disease communities with a high unmet medical need. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.