Elate Ocular™ - Cambium’s Biologic Eye Drop for Dry Eye Syndrome
Elate Ocular™ is a pro-regenerative allogeneic (not autologous) human platelet derived topical ophthalmic product intended for use in treating the symptoms of chronic dry eye as well as numerous other corneal diseases. This product is formulated from the novel processing of base human platelets sourced from healthy and generally younger eligible donors (versus patients) from U.S. blood collection centers. One major advantage of sourcing base platelets from blood collection centers versus individual patients--is the significant thoroughness and redundancy in safety screening, testing, storage and handling measures of blood products mandated by the FDA that already takes place at these centers prior to receipt by Cambium. Then upon receipt and throughout Cambium’s GMP manufacturing process additional tests and safety measures are implemented to further insure product quality, consistency, standardization—and to additionally lessen the risk of product-based complications. The resultant product is called Aurarix™ Cambium’s novel processed human platelet lysate. Aurarix™ is then further formulated into Elate Ocular™ biologic eye drop for dry eye, for UltraGRO Advanced™ for sale by Cambium’s strategic partner as a cell growth supplement, and for potential additional therapeutic applications in the near future.
There is one aspect of Cambium’s novel process that makes Aurarix™ ideal for numerous therapeutic applications versus today’s standard platelet-derived products. Cambium’s novel process depletes fibrinogen from human platelet lysate. Fibrinogen is the “clotting” agent in platelets. And while this role remains vital for platelets in humans, it serves no meaningful therapeutic role present in a topical eye drop for dry eye as an example. In fact, its presence in autologous serum drops can negatively impact remaining levels of beneficial nutritive and regenerative components desired in these products. And because fibrinogen is removed in Cambium’s processing, Elate Ocular™ ends up with not equivalent but enriched levels of beneficial components and with less/none of the detrimental ones. Additionally, a shelf-stable formulation of Elate Ocular™ (versus one requiring freezing/refrigerator storage as mandated for serum drops today)—will be available for Elate Ocular™ is expected to be available by first commercialization. Finally, while reimbursement coverage by major healthcare payers cannot be guaranteed at this time—Cambium believes its Elate Ocular™ will receive eventual reimbursement coverage unlike today’s serum drops based on preliminary investigations.
While it must be stressed that Elate Ocular™ remains today in development, remains today a investigational biologic unapproved for clinical use and will require clinical support and eventual FDA approval to support the following and for commercialization—a hypothetical comparison of what Cambium anticipates in its Elate Ocular™ versus other leading dry eye therapies is provided below:
Dry Eye Syndrome
Dry eye or keratoconjunctivitis sicca (KCS or Dry Eye Syndrome) is one of the most frequently encountered eye diseases. Twenty–five (25%) percent of all patients who visit ophthalmic clinics report symptoms of dry eye, making it the number one reason people see their eye care practitioner outside of vision correction. Largely because dry eye is associated with aging, it continues to be a growing public health problem severely impacting patients and in certain cases a patient’s quality of life. Dry eye affects an estimated 25 million people in the US today. It prevalence is about 9% of the total US population but upwards of 33%+ in people over 65. Interestingly, its prevalence is 33% among total populations in certain Pacific Rim countries including China. According to CBDM.T, dry eye represents one of the fastest growing pharmaceutical product categories in the ophthalmology market today. MarketScope estimates the worldwide market at $2.4 billion in 2013, projected to grow to $3 billion by 2018.
Dry Eye Syndrome is chronic and has no cure. It is caused by either the reduction in tear aqueous production/volume over time or the degeneration of tear lipid (oil layer) components—again typically associated with aging. Therapies today focus largely on treating symptoms (e.g., burning, gritty, itchy, foreign body sensations, and blurred vision) versus causes since there is no cure. Major therapies to date are 1) OTC artificial tears/lubricants/wetting drops; 2) cyclosporine and/or corticosteroids drugs to treat inflammation, just one of numerous contributors or aggravators of dry eye; 3) punctal plugs to help increase tear film volume; and finally autologous serum drops. While autologous serum drops have been well documented in the literature for over 30 years as generally safe and effective for dry eye, they remain to date a niche therapy largely for failed med patients due to certain historical limitations.
For more information on dry eye (keratoconjunctivitis sicca), please go to:
- Dry Eye Syndrome, American Academy of Ophthalmology
- Dry Eye, American Optometric Association
- Facts About Dry Eye, National Eye Institute (NEI)
- Dry Eye Syndrome, AllAboutVision.com
- Dry Eye, WebMD
Autologous Serum Drops
Autologous serum drops are made from a patient’s own blood, processed, diluted, packaged and then returned to that same patient. In this approach platelets are collected from a patient by their clinician, centrifuged to remove certain unwanted components resulting in a platelet-enriched-plasma. This is then diluted, packaged in preservative free packaging, frozen and finally dispensed back to the individual patient on a 2-3 month basis. The following illustrates the process:
Since platelets used in autologous serum are patient sourced, patients must return to their clinician every 2-3 months to re-donate blood for product “refills.” Serum drops in spite of these and other limitations, have been well documented in the literature for over 30 years as generally safe and effective for dry eye as well as many other corneal diseases. A major reason they are generally considered safe and effective, unlike any other dry eye therapeutic on the market today—is that they contain and mimic the numerous nutritive and regenerative components already present in healthy tear film—see below:
Cambium, however, feels that “autologous” serum (emphasis autologous) is and will always remain a niche “last ditch” therapy for dry eye in spite of generally positive safety and efficacy data for numerous historical limitations as listed below:
Historical Limitations of Autologous Serum
- Base platelets are sourced from older diseased patients. As a result, trace amounts of systemic drugs often used by older patients (e.g., hypertension, depression, antihistamines, decongestants, hormones, pain relievers, corticosteroids and others) can end up as trace amounts in autologous serum causing or aggravating the treatment of dry eye symptoms potentially compromising some beneficial effects of serum drops.
- Absence of large, multi-site, randomized, peer-reviewed, masked clinical studies continues to contribute to a certain amount of caution or skepticism regarding serum drops.
- No FDA approvals.
- No industry acknowledged standards regarding the sourcing, collection, processing, shipping, storage or dosing of platelet based products.
- Lack of product consistency batch-to-batch over time even for serum drops derived from the same patient.
- Inconveniences, invasiveness of having to donate one’s own blood every 2-3 months.
- Current requirement to store and keep serum drops frozen, then thawed before use (i.e., no shelf stable serum drops exist today).
- No GMP manufacturing.
- Finally and very important--no reimbursement due in part to the lack of standardization, resulting in patients today having to pay out-of-pocket as much as $600/quarter for their serum drops.
Cambium believes that by addressing these limitations, a standardized commercialized FDA approved superior version of serum drops very much has the potential of becoming an exciting, main stage therapy for dry eye going forward.
While articles and studies on autologous serum drops go back as early as 1984 (Fox), the following provides a sampling of articles on autologous serum drops since 2003:
- Autologous Serum Eye Drops for the Treatment of Ocular Surface Disease, Eye & Contact Lens, May 2015.
- The Efficacy of Autologous Serum Eye Drops for Severe Dry Eye Syndrome: A Randomized Double-Blind Crossover Study, Graefe Archive of Clinical and Experimental Ophthalmology, February 2014.
- The Application of Autologous Serum eye Drops in Severe Dry Eye Patients; Subjective and Objective Parameters Before & After Treatment, Current Eye Research, January 2014.
- Use of Autologous Serum in the Treatment of Ocular Surface Disease, Archives of Ophthalmology, December 2012.
- Autologous Serum Eye Drops Reduce Ocular Surface Disease Symptoms, Primary Care Optometry News, October 2012.
- Allogeneic Serum eye Drops for the Treatment of Dry Eye Patients with Chronic Graft-Versus-Host Disease ,Journal of Ocular Pharmacology and Therapeutics, June 2012.
- Autologous Platelet Lysate for Treatment of Refractory Ocular GVHD, Bone Marrow Transplantation, April 2012.
- Autologous Serum for Ocular Surface Diseases, Arqulvos Brasileiros de Oftalmologia, November/December 2008.
- Autologous Serum Eye Drops for the Treatment of Dry Eye Diseases, Cornea, September 2008.
- Use of Autologous Platelet-Rich Plasma in the Treatment of Dormant Corneal Ulcers, Ophthalmology, July 2007.
- Symptomatic Dry Eye Treatment with Autologous Platelet-Rich-Plasma, Ophthalmic Research, March 19, 2007.
- The Use of Autologous Serum Tears in Persistent Corneal Epithelial Defects, Eye, 2004.
- Autologous Serum Eye Drops for Ocular Surface Disorders, British Journal of Ophthalmology, November 2004.
- Comparison of Autologous Serum Eye Drops with Conventional Therapy in a Randomized Controlled Crossover Trial for ocular Surface Disease, British Journal of Ophthalmology, May 2004.
- Autologous Serum Eye Drops for the Treatment of Severe Dry Eye in Patients with Chronic Graft-versus-Host Disease, Bone Marrow Transplant, April 2003.