Spring How will that pipeline drug impact my benefit plan?

Transcription

1 Spring 2012 How will that pipeline drug impact my benefit plan?

2 How will that pipeline drug impact my benefit plan? It can be difficult to predict the impact pipeline drugs will have once they reach the market. Those that get the attention of plan sponsors may be characterized by one or more of the following: treats chronic versus acute disease treats a highly prevalent disease which impacts large numbers of plan members is used early versus later in a disease and, therefore, has more potential for exposure to larger numbers of plan members has an associated high price tag, or has a significant annual cost New drugs in the pipeline that treat chronic, prevalent diseases of interest are described in Table 3. If successful and these drugs in future are authorized for sale in Canada by the Therapeutic Products Directorate (TPD) of Health Canada, pricing would be up to the manufacturers; however, the manufacturers are accountable to the Patented Medicine Prices Review Board (PMPRB) for the prices that are set. Pricing: patented medicine prices review board The Patented Medicine Prices Review Board (PMPRB) is an independent quasi-judicial body established by Parliament in 1987 under the Patent Act that sets the maximum price of patented medicines in Canada. The PMPRB regulates the prices set by the pharmaceutical manufacturers, and does not have jurisdiction over prices charged by wholesalers or pharmacies, or over pharmacists professional fees. Two reviews: the scientific review process and the price review process are performed to determine that the prices set by the pharmaceutical manufacturers are not excessive. The scientific review process An evidence-based process that assesses the level of therapeutic improvement of a patented drug product and recommends, where appropriate, the drug products to be used for comparison purposes and the comparable dosage regimens. The levels of therapeutic improvement are: Breakthrough: A breakthrough drug product is the first one to be sold in Canada that treats effectively a particular illness or addresses effectively a particular indication. There will be no drug products recommended for comparison purposes for a new patented drug product that represents a breakthrough, given that such a drug product is, by definition the first one to be sold in Canada that treats effectively a particular illness or addresses effectively a particular indication. Substantial Improvement: A drug product offering substantial improvement is one that, relative to other drug products sold in Canada, provides substantial improvement in therapeutic effects. Moderate Improvement: A drug product offering moderate improvement is one that, relative to other drug products sold in Canada, provides moderate improvement in therapeutic effects. Slight or No Improvement: A drug product offering slight or no improvement is one that, relative to other drug products sold in Canada, provides slight or no improvement in therapeutic effects. Any drug product that is not considered a breakthrough and that is not considered to offer substantial or moderate improvement will fall into the category of drug products offering slight or no improvement. Perspective Spring

3 If no comparable drug products are found, the review will proceed by identifying all drug products that are considered superior in treating the same approved indication for use as the new patented drug product under review, and is based on factors such as providing increased efficacy and reduction in incidence or grade of important adverse reactions. The price review process The level of therapeutic improvement of a patented drug product is then used to determine the Maximum Average Potential Price at introduction. Following introduction, the price of an existing patented drug product is reviewed according to the relevant price tests to establish the National and Market-Specific Non-Excessive Average Prices. The factors that must be taken into consideration when determining whether a patented medicine is being sold or has been sold at an excessive price in any market in Canada by a patentee or former patentee include but are not limited to: The prices at which the medicine has been sold in the relevant market; The prices at which other medicines in the same therapeutic class have been sold in the relevant market; The prices at which the medicine and other medicines in the same therapeutic class have been sold in countries other than Canada; Changes in the Consumer Price Index The Canadian price that is set by the manufacturer, and then subsequently assessed by the PMPRB to ensure that it is not excessive is dependent on the level of therapeutic/clinical benefit of the drug over what currently exists, as well as the price of those comparable products that are already on the market both in Canada and abroad. (For more information on the PMPRB and its processes, the reader is encouraged to visit the PMPRB website ) Perspective Spring

4 Table 3: Pipeline Drugs and Indications of Interest on the Horizon Generic Name and Therapeutic Manufacturer Current Anticipated Use and Status Mode of Action Treatments Comments Impact Tofacitinib (formerly called tasocitinib) for Rheumatoid Arthritis Pfizer Under review by the European Medicines Agency Under review by the US Food and Drug Administration (FDA) First in a new class - Janus kinase 3 (JAK3) inhibitors Targets the inflammatory cascade Disease-modifying anti-rheumatic drugs (DMARDs): e.g. methotrexate Biologics: Enbrel, Humira, Cimzia, Orencia, Kineret, Rituxan, Remicade, Simponi May be the first new oral DMARD to be marketed in more than 10 years. Presents an oral alternative to existing injectable biologics. Preliminary studies showed comparable efficacy as Humira. Other uses: chronic plaque psoriasis and other inflammatory diseases Moderate Rheumatoid arthritis drugs account for 8.1% of total DIN cost paid on the TELUS book of business (2011) Dapagliflozin for Diabetes Bristol-Myers Squibb and AstraZeneca Declined by the FDA, requesting more data about the drug s riskbenefit profile First in a new class - sodium glucose cotransporter-2 (SGLT-2) inhibitors Blocks glucose reabsorption in the kidneys and causes glucose to be eliminated through the urine Insulin Action: thiazolidinediones (e.g. Actos, Avandia), metformin Insulin Release: incretin mimetics (e.g. Byetta, Victoza), sulfonylureas (e.g., Diabeta), dipeptidyl peptidase-4 inhibitors (e.g. Januvia, Onglyza, Trajenta), meglitinides (e.g. Gluconorm, Starlix) Unique mechanism of action compared to existing anti-diabetic agents May be associated with weight loss May also have a diuretic and hypotensive effect Possible risk of breast cancer and bladder cancer Moderate Diabetes drugs account for 5.0% of total DIN cost paid on the TELUS block of business (2011) Insulin Replacement: Insulin Apixaban (Eliquis) for Stroke Prevention in Atrial Fibrillation (Indication pending approval) Bristol-Myers Squibb Canada Approved by Health Canada to help stop blood clots from forming after hip or knee replacement operations, thereby preventing deep vein thrombosis and pulmonary embolism (December 16, 2011) An oral direct factor Xa inhibitor Factor Xa is the main site of amplification in the coagulation cascade warfarin (Coumadin), dabigatran (Pradax), rivaroxaban (Xarelto) In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism and resulted in lower mortality Less bleeding than warfarin No INR monitoring required Moderate Blood thinners account for 2.1% of total DIN cost paid on the TELUS block of business (2011) Perspective Spring

5 What will be the price of the pipeline drugs when they enter the Canadian market and might they be deemed as excessive by the PMPRB? While we cannot guarantee an accurate prediction of the prices upon market entry; nor whether the PMPRB would consider them to be excessive due to the numerous factors that the PMPRB considers, we can consider the pipeline drugs in the context of their indication(s) ( i.e., what diseases they treat), their potential place in therapy and prices of products that are already on the market in Canada. Tofacitinib for rheumatoid arthritis Tofacitinib is an oral (i.e., not a biologic) treatment currently being studied for rheumatoid arthritis. Based on the currently available products, the older disease-modifying anti-rheumatic drugs (DMARDS) have an annual cost in the thousands of dollars, while the newer anti-tnf therapies have significantly higher annual costs as reported by the Canadian Association for Drugs and Technologies in Health (CADTH) (see table 4 below and available on the internet at Clinical_and_Economic_Overview_e.pdf). To use the PMPRB framework, the first consideration would be to determine if it is perceived as breakthrough or as a substantial improvement etc. The key clinical question that will impact the price will be if and to what degree it provides an improvement over the currently existing treatments. As part of the clinical trial program for tofacitinib, two phase III studies (yet to be published gen-news-highlights/two-phase-iii-studies-confirm-benefits-of-pfizer-s-tofacitinib-against-active-ra/ /) have compared it to placebo and placed it after treatment with methotrexate has failed/no longer responsive, as well as after failure of a tumor necrosis factor (TNF) inhibitor (biologic). The second study included both tofacitinib and one of the biologic agents, adalimumab, however, the primary outcome of the study was not a direct comparison between the two active agents; therefore, making it challenging to definitively conclude on how they compare to each other. ( ticleid=c4f92d c d4cc5dc). Based on the above, tofacitinib will likely be positioned after the first line DMARDS (e.g. methotrexate). In the absence of data to support a direct comparison between tofacitinib and one of the biologics, it is difficult to determine if tofacitinib is equal or superior to the biologics and would, therefore, command a an equal or higher annual price as compared to the biologics. If the clinical effect of the drug is considered a moderate improvement, the price point might be set somewhere between methotrexate and the biologics. A slight or no improvement, however, would likely result in pricing at par with methotrexate. Additional considerations may include whether the oral property of the drug (i.e., a non biologic drug) requiring less complicated manufacturing and an easier supply chain relative to the expensive biologics would temper the price point. If tofacitinib was deemed to be approximately equal to the biologics, again would the oral (i.e. non biologic) property impact on the potential maximum price? We can conclude with certainty that the annual cost will be higher than that of methotrexate, however, how much higher will be determined by factors including those discussed above. Perspective Spring

6 Table 4: Cost Comparison Drug Health Canada First Year Subsequent Year (Brand Name) Price Recommended Doses Annual Cost Annual Cost Adalimumab $ per 40 mg 40 mg sc every 2 weeks $18,388 $18,388 (Humira) syringe or pen Certolizumab $ per 200 mg 400 mg sc at weeks 0, 2, and 4, $19,271 $17,277 pegol (Cimzia) syringe then 200 mg every 2 weeks Etanercept $ per 50 mg 50 mg sc once weekly $18,943 $18,943 (Enbrel) syringe or pen* $ per 25 mg vial 25 mg sc twice weekly $20,486 $20,486 Golimumab $1, per 50 mg 50 mg sc once monthly $17,364 $17,364 (Simponi) syringe or pen Infliximab $ per 100 mg vial 3 mg/kg IV infusions 70 kg patient $23,472 $17,604 (Remicade) at weeks 0, 2, and 6 then 3 mg/kg every 100 kg patient $23,472 $17,604 8 weeks DOSE ESCALATION 70 kg patient NA $31,296 5 mg/kg every 6 weeks 100 kg patient NA $39,120 in subsequent years Rituximab $ per 100 mg vial 1,000 mg IV at weeks 0 and 2 (first course). $9,438 (1 course) $9,438 (1 course) (Rituxan) Can be repeated 5 to 6 months after to $28,314 to $28,314 previous treatment (3 courses) (3 courses) Abatacept $ per 250 mg vial 500 mg every 4 weeks IV < 60 kg patient $12,412 $12,412 (Orencia) 750 mg every 4 weeks IV 60 kg to $18,619 $18, kg patient 1,000 mg every 4 weeks IV > 100 kg patient $24,825 $24,825 Anakinra $50.99 per 100 mg 100 mg sc daily $18,611 $18,611 (Kineret) syringe IM = intramuscular; IV = intravenous; NA = not applicable; sc = subcutaneous. Note: Costs presented in this table do not include the costs of administration. Source: Saskatchewan Drug Benefit (February 2010). * Ontario Drug Benefit (February 2010). Provided by manufacturer. Costs assume wastage of partially used vials. Where wastage does not occur, the annual cost for a 70 kg patient would be $12,323 at a maintenance dose of 3 mg/kg every 8 weeks. Based on expert opinion, usual dose escalation of infliximab in clinical practice is approximately 5 mg/kg every 6 weeks and rarely reaches 10 mg/kg every 4 weeks. At a maintenance dose of 10 mg/kg every 4 weeks, annual costs would be $88,998 for a 70 kg patient and $127,140 for a 100 kg patient. Source: Canadian Agency for Drugs and Technologies in Health. Therapeutic Review CLINICAL AND ECONOMIC OVERVIEW Biological Response Modifier Agents for Adults with Rheumatoid Arthritis July 2010* * An amendment was made in November 2010 Dapagliflozin for diabetes The daily costs* and currently available medications include: metformin (<$1.00), sulfonylureas (<$1.00), thiazolidinediones (<$3.00), dipeptidyl peptidase-4 (DPP-4) inhibitors (<$3.00), liraglutide ($4.89 to $7.34), insulin NPH (<$2.00), and insulin analogues (<$3.00). The US Food and Drugs Administration (FDA) reviewed dapagliflozin for licensing and approval in the United States. As part of the review, the clinical trial program, submitted by the manufacturers to the FDA, was made up of 11 studies. The FDA focused on 6 studies in particular. In these studies, dapagliflozin was used after failure (i.e. not getting blood sugars down low enough) of the following therapies: monotherapy (i.e. no previous therapy), metformin, thiazolidinediones, insulin and up to two oral therapies. (FDA Advisory Committee Meeting Dapagliflozin July 19, 2011). As can be seen from the clinical trial program, the therapy could potentially be an option for use anywhere along the treatment course for patients, from the potential first therapy, to an add-on therapy to other agents. The studies with HbA1c as the primary endpoint, led the FDA to conclude that dapagliflozin is effective in subjects with normal renal function or mild impairment. Perspective Spring

7 One of the most recent hypoglycaemic products on the Canadian market is liraglutide (a subcutaneous formulation) with the range of daily cost noted above, is also the first in a new class of drugs, as would be the case with this new drug, dapagliflozin. As can be seen, the daily cost of liraglutide is well above those products that were already on the market. Of note, liraglutide received a final recommendation from the Common Drug Review (CDR) (September 28, 2011) that the product not be listed at the submitted cost. The place in therapy for dapagliflozin remains to be determined. It potentially could be positioned earlier during the patient s treatment (when kidney function is at its best and the drug would likely work best due to the dependency on kidney function). Due to safety concerns [the FDA subsequently declined approval of dapagliflozin largely because of fears that it may cause breast and bladder cancer and has asked the filing companies (AstraZeneca and Bristol Myers Squibb) for additional information)], however, it may be positioned for use once the patients are progressing on other therapies. Another variable that might factor into the price set by the manufacturer is the negative recommendation from the Common Drug Review (CDR) based on price for other recent hypoglycaemic therapies. Due to the request for additional data driven by safety concerns, it remains to be determined if the drug will be approved for market. If the safety concerns are addressed, the price of dapagliflozin will likely be at least that of the DPP-4. Apixaban for stroke prevention in atrial fibrillation We can consider the cost of other anticoagulants that have come to the Canadian market recently for the indication of stroke prevention in atrial fibrillation (AF). Apixaban belongs to the same drug class as rivaroxaban; both are direct factor Xa inhibitors. PMPRB classified rivaroxaban as a category 3 new medicine as it provides moderate, little or no therapeutic advantage over other available therapies. Rivaroxaban was approved for stroke prevention in AF earlier this year and is priced at $3.00/day.** Its review is currently underway by CDR. Dabigatran, from the new direct thrombin inhibitors class, received approval in 2010 for stroke prevention in AF. The daily cost of dabigatran is $3.38.** Dabigatran was reviewed in June 2011 by CDR and the recommendation was positive (i.e. to list with criteria), even though it is priced significantly higher than warfarin, the mainstay of therapy, available at pennies a day. The 2012 Update of the Canadian Cardiovascular Society Atrial Fibrillation Guidelines addressed the place in therapy of the newer oral anticoagulants: apixaban, rivaroxaban, and dabigatran. Compared with warfarin, both dabigatran and apixaban are more effective than warfarin for the prevention of stroke while rivaroxaban is noninferior to warfarin. Apixaban causes less major bleeding than warfarin. Compared to warfarin, there is no more major bleeding with either dabigatran or rivaroxaban. The guidelines do not indicate a preference for one drug over the other, even though apixaban is more efficacious and has less bleeding. We can anticipate that the pricing of apixaban for stroke prevention in AF will likely be comparable to the pricing of rivaroxaban and dabigatran. What does this mean for plan sponsors Understanding the where and when a potential new drug will be used to treat a disease before its launch, as well as the potential price tag, might help estimate the potential impact to individual employer-sponsored drug plans. We look forward to reporting on future pipeline drugs of interest. Suzanne Easo, B.Sc.Phm., R.Ph. * Source: CADTH CEDAC FINAL RECOMMENDATION LIRAGLUTIDE (Victoza Novo Nordisk Canada Inc.) available on the internet at ** based on Ontario pricing before mark-ups Perspective Spring

8 Information for life TELUS Health is a leader in telehomecare, electronic medical and health records, consumer health, benefits management and pharmacy management. TELUS Health give health authorities, providers, physicians, patients and consumers the power to turn information into better health outcomes. For more information about TELUS Health, please visit telushealth.com. This article printed as part of Perspective - Spring 2012 issue. TELUS All rights reserved. Printed in Canada.