May_jun_06.qxd

Therapeutic
Although clinical practice guidelines for Specialty Pharma Opportunities
the prevention and treatment of CINV haveimproved over time, actual adherence in this in Cancer Supportive Care:
regard lags behind (Figure 1). Improvementin risk assessment and stricter adherence toguidelines for the prevention and management A Look at Anti-Emetic Therapy
of both acute and delayed CINV, particularlyfor initial courses of treatment, may ultimatelylead patients to an improved quality of life By: Suresh Borsadia, President & CEO; and during therapy, a reduction in time spent by healthcare providers addressing CINV, and Strategic Planning & Alliance Management, patients to optimal therapeutic doses for themanagement of their disease.4 Emesis Classification
Introduction
treatment for their disease because of the & Physiology
quality of life caused by CINV, ultimately phases: acute, delayed, and anticipatory.5 common and distressing side effects of cancertreatment. The current market size of CINVtherapeutics is more than $1.5 billion in theUS alone.1 An estimated 70% to 80% of patients receiving chemotherapy experiencesome level of nausea and vomiting.2 AcuteCINV significantly reduces quality of lifeduring treatment, and delayed CINVcontinues to be an issue after patients return home following their treatment, affecting their ability to perform daily activities.
Furthermore, metabolic disturbances, suchas electrolyte imbalances and/or dehydrationmay occur due to CINV, as well as tearingof the esophageal mucosa, rehospitalization,increased medical costs, and increased time commitments by healthcare providers forthe management of events caused by CINV.
However, one of the most disconcerting consequences of CINV is the tendency of upto 50% of the patients to refuse subsequent Figure 1. Chemotherapy-Induced Emesis Nausea & Vomiting (CINV) – Impact on Health-
Related Quality of Life.
efficacy of the 5-HT3s in acute emesis.
induced by a highly emetogenic drug, while Delayed emesis on the other hand, seems to treatment; delayed CINV is defined as nausea and/or vomiting that occurs after the first substance P/neurokinin(NK)1 receptors – 24 hours of treatment and up to 120 hours emesis. Although it was previously thought following treatment; and anticipatory CINV receptor antagonist (aprepitant – Emend®) that 5-HT3 inhibitors were only useful in is defined as nausea and/or vomiting that occurs prior to the delivery of subsequent inhibitor Aloxi® is the first approved drug in Incidence of CINV
its class for the prevention of delayed CINV.
This benefit is likely due to palonosetron’s optimal prophylactic anti-emetic therapy; & Current Treatments
longer half-life and high receptor binding however, breakthrough emesis is difficult to researchers have questioned whether Aloxi’s physicians and nurses routinely underestimate the incidence of delayed nausea and vomiting pharmacologic or simply a carryover effect.
inadequate prophylactic anti-emetic therapy.
between the perceived incidence versus the scientific explanation because there is no body of evidence to show that palonosetron contributing to its development, several of which are currently under investigation. It is the other 5-HT3 inhibitors. Hence, a drug and may not be reporting the side effect to vomiting are two distinct entities. Nausea is sustained levels up to 5 days for any of the Several different types of anti-emetics are a feeling characterized by the urge to vomit.
available today, including 5-HT3 receptor antagonists, corticosteroids, D2 receptor keeping the 5-HT3 receptors saturated, and antagonists, and NK-1 receptor antagonists, sensation, often accompanied by tachycardia, should show benefits in delayed emesis.
sweating, flushing, and/or restlessness.
Vomiting is the actual propulsion of stomach antagonist, represents a new class of anti- contents through the esophagus and out of development in the 1990s of 5-HT3 inhibitors, 2004 to be used in combination with other peripheral and central sites from binding of interactions between neurotransmitters and receptors located in both the peripheral and central nervous systems. Several different chemotherapy, including high-dose cisplatin.
inhibitors are highly effective in prevention including serotonin, dopamine, acetylcholine, or management of acute CINV, particularly The Need Today — Prevention
histamine, and substance P to name a few.
Acute emesis is hypothesized to originate chemotherapy agents. A comparative summary extremely important in maintaining a patient’s of the 5-HT3 inhibitors is provided in Table 1. gastrointestinal (GI) tract post-chemotherapy, quality of life. However, the optimal strategy leading to stimulation of the 5-HT3 receptor in the central nervous system, which triggers acute and delayed CINV in the initial course a nauseaus reflex – hence, the usefulness/ of treatment, rather than treating the problem once it has occurred. First, quality of life and patient compliance to further treatment may be maintained if CINV prevention occurs in Comparison of 5-HT3s
the initial courses of therapy. In addition, Receptor
Routes of
Trade Name
Half-Life
Binding Affinity
preventing CINV can help to reduce medical Administration
cost and the burden of managing CINV.
Dolasetron
Second, prevention of CINV in the initial Ondansetron
course of therapy may lead to reduced CINV Granisetron
experience of CINV with initial courses of Palonosetron
Emerging Treatments
Company Product
Delivery Technology
Potential Uses
Advantages/Disadvantages
• Preventive treatment option that provides protection • Could be easily removed if there is any adverse • Requires specialist healthcare provider for • Requires surgical procedure if removal is necessitated due to any adverse effect from therapy.
• Short duration of action, limited if any, use in • Patient acceptability and taste could present a • Short duration of action, limited if any, use in • Taste-masking could be a major challenge.
• Design increases product cost and complexity of administration with no apparent benefits over a treatment protocols to determine the risk agents are considered moderately emetogenic of their patient developing CINV.10 Once a patient’s risk is determined, healthcare clinical studies. Risk assessments help to determine which patients are at a higher risk Level 1: < 10% frequency of emesis
protocols according to established guidelines.
Level 2: 10% to 30% frequency of
that if CINV is uncontrolled, there is: 1) a patients who are identified through the risk- reduction in scores in cognitive function; Level 3: 30% to 60% frequency of
assessment models may be strictly managed dyspnea; and 6) poor overall quality of life. specified guidelines. Patients identified at idarubicin, ifosfamide, IL-2, irinotecan, also be treated for the prevention of CINV, week on the telephone with their patients at Level 4: >60% to 90% frequency of
The most commonly identified risk factors nurses to have more time to tend to other emesis (amifostine, busulfan, carboplatin, for developing chemotherapy-induced emesis agents used in treatment; 2) prior CINV; Emerging Treatments
3) female patients; 4) younger patients; Level 5: >90% frequency of emesis
possess? The consensus is that an ideal anti- is classified into 5 levels according to the (carmustine, cisplatin, cyclophosphamide, emetic would provide: 1) complete control in all settings; 2) no side-effects; 3) convenience and ease of use; 4) fewer drug interactions; emetogenic agents listed further are from It is important for healthcare providers to 5) a simpler dosing regimen; and 6) no cost the National Comprehensive Cancer Network properly assess their patients and intended products being developed for CINV are drug delivery systems incorporating existing 5-HT3 Specialty Pharmaceutical company active in reformulations, along with their key features the supportive cancer segment, because in are shown in Table 2. It is apparent that a addition to CINV, there exist significant transdermal anti-emetic product comes closest opportunities in radiation-induced nausea Suresh Borsadia
to satisfying the profile of an ideal anti- and vomiting (RINV) and in post-operative emetic product. Abeille Pharmaceuticals, Inc., has a transdermal anti-emetic product at an advanced stage of development. Some of the References
advantages of a transdermal product include:1) an ideal mode of treatment for cases 1. Taller D. Analyst Report from Cathay Financial, Mr. Suresh Borsadia has more than 14 years where the need for the anti-emetic therapy experience in the pharmaceutical and drug extends beyond 1 day, since the patch will 2. Ettinger DS. Chemotherapy-Induced Nausea and delivery industries, with expertise and experience Vomiting (CINV). An update from ASCO; 2004. be designed to deliver the drug for up to 5 in R&D and business/corporate development days; 2) protecting the patient through the 3. www.cancernausea.com – a website for people activities. Mr. Borsadia has a demonstrated experiencing nausea and vomiting caused by chemotherapy until the patch is removed; 3) projects and building R&D organizations in early 4. Buckner CD, Maxon J. Chemotherapy-Induced maintaining blood levels of the drug in the stage companies. Prior to founding Abeille Nausea and Vomiting (CINV): An update from the Oncology Nursing Society (ONS) Pharmaceuticals, Inc., he was with Lavipharm therapy. In addition, the blood levels of the for 7 years, where he played a leading role in the company’s R&D, in-licensing, and out-licensing drug will continue in the therapeutic range 5. ASHP Therapeutic Guidelines on the Pharmacologic Managemnet of Nausea activities. He was part of the Senior Management several hours post removal of the patch; 4) and Vomiting. Am J Health Sys Pharm.
team involved in M&A and fundraising activities.
increasing patient confidence in the ability Prior to that, he worked at two other leading to leave the hospital or the doctor’s office 6. Ellis RJ, Jr. Analyst Report from Leerink Swann drug delivery companies, TheraTech, Inc., (now Watson Pharmaceuticals), and Bertek, Inc., knowing that they will not require further 7. Grunberg S, et al. Incidence and impact of (now Mylan Technologies, a Division of Mylan intervention for side-effects; 5) improving nausea/vomiting with modern antiemetics: Labs.). His professional background is in perception vs. reality. Cancer. 2004;100:261-268. removing the need for an oral administration 8. Gralla R. New antiemetic agents. Clin Adv Hematol Oncol. 2005;3(5):350-352, 382. of an anti-emetic during a time period whenthe patient may not want to ingest anything due 9. National Comprehensive Cancer Network, to discomfort; 7) helping reduce anticipatorynausea in subsequent chemotherapy treatments; 10. Lindley CM, et al. Quality of life consequences Kalpana Patel, PhD
of chemotherapy-induced emesis. Qual Lif Res.
and 8) easily removed by the patient if there is any adverse effect due to the therapy. Strategic Planning & AllianceManagement, AbeillePharmaceuticals, Inc.
Dr. Kalpana Patel has more than 12 years of experience in the pharmaceutical industry and has led preformulation, formulation, process development, and validation initiatives for a range of Rx, Rx to OTC switches, OTC products, and medical devices. Dr. Patel most recently was the Pipeline Development Director for Johnson & Johnson Consumer Companies.
During her tenure at J&J, she held leadership responsibilities involving product development, life cycle management, and was involved in advisory meetings with thought leaders. In addition, she was actively involved in interaction with global regulatory bodies. While at J&J, she also founded the Johnson & Johnson community Figure 2. Perceptions & Reality - Moderately Emetic Chemotherapy.

Source: http://www.abeillepharma.com/news/Speciality%20Pharma%206-06%20Low-Res.pdf