Pricing and Reimbursement Assessment for Roche s RO507 in Germany. Final Report Excerpt

Transcription

1 Pricing and Reimbursement Assessment for Roche s RO507 in Germany Final Report Excerpt February 29, 2008

2 Current Treatment and Reimbursement Situation in Germany Final Report_Roche Diabetes February 29,

3 Disregarding cost, the clinical value of GLP-1 analogs is perceived to be comparable to that of DPP-IV inhibitors and sulfonylureas Perceived performance of sulfonylureas, GLP-1 analogs and DPP-IV inhibitors differs between payers and s. Metformin and Lantus receive consistently the most favorable value assessment. Overall Clinical Performance Feedback on Clinical Performance of Byetta Metformin Long-acting insulin (Lantus, Levemir) Short-acting insulin (Humalog) Sulfonylureas GLP-1 analogs (Byetta BID) DPP-IV inhibitors (Januvia, Galvus) Meglitinides (NovoNorm, Starlix) Glitazones (Actos, Avandia) Payers Payers s s Payers s 3.8 "I like the effects of Byetta. Maybe it even helps to reduce insulin and can therefore be more cost-effective." - "Byetta is a new substance and in general very interesting with its non-insulinotrophic effect. " - Payer "I like the fact that Byetta reduces weight rather than increasing it, unlike other substances we use." - α-glucosidase inhibitors (Glucobay) "Apparently rosiglitazone causes exactly what we always thought it would prevent: CV risk." - Not satisfied at all Average Rating (n = 8) Very satisfied "Byetta has a new mechanism of action with good effects on several parameters, but its impact and value for the T2D treatment strategy still have to be determined." - Payer Final Report_Roche Diabetes February 29,

4 Cost, safety and HbA1c reduction are most important to payers Mode and convenience of administration are less important when evaluating the value of new antidiabetics. In addition, payers and s views differ significantly. Relevance of Value Drivers Therapy costs/day Safety (e.g. risk of pancreatitis, bone fracture) Sustained reduction of HbA1c level Immunogenic risks HbA1c level: Overall average reduction Impact on micro and macrovascular events / relative risk HbA1c level: Share of patients treated to target Frequency of hypoglycemic events Improved performance on fasting plasma glucose levels Tolerability (e.g. GI side effects) Weight reduction Improved performance on postprandial plasma glucose levels Improved patient compliance Effect on non-conventional biomarkers of cardiovascular risk Effect on beta-cell function / preservation Mode of administration (oral, injectable, inhaled, pumps) Improved performance on lipid levels Quality of life Convenience of administration (e.g. device, # of admin) Payers s Less important Importance Rating (n = 8) Very important "Higher treatment costs are difficult to justify in T2D. We have less expensive options with good clinical profiles." - Payer "Compliance advantages of different administration frequencies have not been demonstrated in clinical trials." - Payer "No therapy has shown beta-cell protection so far. This would be fantastic." - "Weekly dosing doesn't mean better compliance for me." -Payer "Weekly dosage is not something we are used to and not necessarily an advantage, especially in the T2D treatment strategy." - Payer Final Report_Roche Diabetes February 29,

5 Byetta has the poorest cost-benefit ratio of all T2D drugs, especially for payers Although metformin and SU generics set the price benchmark, insulin analogs are still seen to have a fair cost-benefit ratio. Perceived Cost-Benefit Ratio Metformin Sulfonylureas Long-acting insulin (Lantus, Levemir) Short-acting insulin (Humalog) DPP-IV inhibitors (Januvia, Galvus) α-glucosidase (Glucobay) Glitazones (Actos, Avandia) Meglitinides (NovoNorm, Starlix) GLP-1 analogs (Byetta) "The therapy costs of Byetta are outrageous." - Payer Payers 2.2 Payers Payers Cost not justified at all s s s Average Rating (n = 8) Cost fully justified "Rebate contracts have worked well for the insulin analogs." - Payer "Januvia was priced lower than expected considering its novel mechanism of action." - "Even glitazones are already too expensive for the clinical value they deliver." - Payer "Byetta would have gained broader access at a lower price." - "Byetta is much too expensive given that it has only a limited added value with respect to other treatment options." - Payer "Lilly certainly did not make a very smart pricing move here." - Final Report_Roche Diabetes February 29,

6 The G-BA imposed a very restrictive therapy advice on the use of Byetta Based on the high therapy costs and stating a lack of evidence, the G-BA recommended Byetta for obese patients with weight gain on high-dose insulin therapy only. Summary of the Therapy Advice on Byetta BID Restricted to patients with uncontrolled weight gain on insulin combination therapy: "The Byetta therapy advice was clearly based on economic arguments first and on clinical arguments second." - Payer " for Type II diabetes patients who are severely overweight (BMI > 30) and show further weight gain on a combination therapy of an oral antidiabetic and insulin ( 1IU/kg). In those cases only, switching from insulin to exenatide in combination with metformin can be justified from a medical and economic point of view." Rationale of the G-BA decision: Lack of cost-effectiveness: 3 to 5 times more expensive than insulin analogs and human insulin, respectively Unfavorable side-effect profile: Frequent gastro-intestinal side effects, comparable to insulin in terms of frequency of hypoglycemia Unclear benefits of weight-loss effect: Risk reduction of cardiovascular morbidity and mortality through weight-loss effect remains to be demonstrated in clinical trials Incomplete clinical profile: Non-inferiority vs. insulin shown, full therapeutic value unclear due to lacking clinical data on long-term benefit and safety Source: Oct. 18, Final Report_Roche Diabetes February 29,

7 Payers consider Byetta's therapy advice justified; s do not agree Although payers admit that primarily financial considerations are part of the therapy advice decision, they still consider the patient definition to be supported by the clinical profile of Byetta. s s feel restricted by Byetta's current therapy advice, since the therapy advice limits use far beyond the clinically eligible patient population However, they agree that Byetta BID was priced too high, restricting its market access due to the fact that German physicians have become very price-sensitive lately s estimates about the size of the population stipulated in the TA are somewhat inconsistent "The therapy advice is not justified at all by Byetta s clinical profile. It should be used much earlier. Furthermore, it can be misunderstood." - "Even private sickness funds have been denied access to Byetta lately." - "The criteria of this group are too narrow. Some of Byetta s potential is not harnessed effectively." - Payers Payers admit that Byetta BID's therapy advice is mostly driven by economic arguments Byetta BID is seen as an interesting product due to its noninsulinotrophic effect with a prohibitively high price The current therapy advice helps to reduce 'misuse' of Byetta: Sickness funds confirmed in individual reviews of physician prescription data that patients had often received Byetta without fully exploiting the therapeutic potential of other, lower-priced antidiabetics "I believe the therapy advice is fully justified." - Payer "The therapy advice is used to push the product into an ideal area based on the high cost of the product." - Payer "The therapy advice is primarily influenced by economic prescribing arguments." - Payer Final Report_Roche Diabetes February 29,

8 Value and Price Perception Final Report_Roche Diabetes February 29,

9 Payers and s state that Byetta BID does not have a direct clinical comparator as the first-in-class GLP-1 analog. Interviewees primarily chose higher-priced anti-diabetes drugs as comparators. However for liraglutide, Byetta BID is unsurprisingly the most relevant comparator. Relevant Clinical Comparator Byetta BID Liraglutide Long-acting insulin (Lantus, Levemir) Short-acting insulin (Humalog) DPP-IV inhibitors (Januvia, Galvus) GLP-1 analogs (Byetta) No comparator n/a "Difficult to compare. It is a drug for special cases, not for a broad patient population." - Payer "Actually there is no comparator. It s a first-inclass product." - Payer "It is usual to compare a new product with other products in the same class, although you might get a different picture if efficacy was compared." - Payer "It's a first-in-class product. You could compare it to DPP-IVs considering the MoA, or you could compare it to intensified insulin therapy." - Multiple answers possible (n = 8) Multiple answers possible (n = 8) Respondents were also prompted with metformin, sulfonylureas, α-glucosidase inhibitors, meglitinides and glitazones. Final Report_Roche Diabetes February 29,

10 Liraglutide is perceived to be rather similar to Byetta BID Reduced dosing as well as better side-effects and HbA1c-reduction are noticed, but they are not perceived as a break-through. Relative Clinical Value Perception* Clinical Value Perception: Liraglutide vs. Byetta BID Clearly superior Slightly superior Equal n = vs. Byetta BID 0.9 Liraglutide "The side-effect profile looks better than Byetta's." - "It's not a breakthrough, marginally better. -Payer "Better doing but not a significantly better efficacy." - HbA1c should actually not be used to market a new drug. The pharmaceutical industry is far too focused on HbA1c. Insulin does the best HbA1c reduction." - Key Value Feedback Liraglutide's clinical profile seen as similar to that of Byetta BID s and payers regard once-daily dosing as an advantage over BID "Marginal differences, maybe a little bit better than Byetta, but this does not justify a higher price. - Payer "The reduced dosing is an advantage. - Payer * Value scale: -2: clearly inferior, -1: slightly inferior, 0: equal, +1: slightly superior, +2: clearly superior Final Report_Roche Diabetes February 29,

11 RO507 and Byetta LAR are both benchmarked against the other GLP-1s The intra-class comparison (comparing RO507 to weekly and daily administered products) is most relevant in a more crowded market. Relevant Clinical Comparator Byetta BID Liraglutide Byetta LAR RO507 Long-acting insulin (Lantus, Levemir) Short-acting insulin (Humalog) DPP-IV inhibitors (Januvia, Galvus) "The direct comparison with the other GLP-1 analogs is obvious. I think it is very likely that they will be grouped in one FRP group if the price difference between products is large." - Payer Byetta BID n/a Liraglutide n/a n/a Byetta LAR n/a n/a n/a No comparator Respondents were also prompted with metformin, sulfonylureas, α-glucosidase inhibitors, meglitinides and glitazones. Multiple answers possible (n = 8) Final Report_Roche Diabetes February 29,

12 RO507 and Byetta LAR both appear to be clearly superior to Byetta BID and liraglutide whereas RO507 is only a minor improvement over Byetta LAR. Summary: Clinical Value Perception Relative Clinical Value Perception* Clearly superior Slightly superior Equal n = 8 Key Value Feedback vs. Byetta BID 1,6 vs. liraglutide 1,5 Byetta LAR Weekly dosing considered clearest advantage over Byetta BID and liraglutide Additional efficacy in terms of HbA1c and weight reduction also mentioned Immunological risks mentioned as a potential concern vs. Byetta BID 1,6 vs. liraglutide 1,6 RO507 * Value scale: -2: clearly inferior, -1: slightly inferior, 0: equal, +1: slightly superior, +2: clearly superior vs. Byetta LAR 0,4 Same dosing advantage as Byetta LAR over BID and liraglutide 507's clinical profile considered quite similar to Byetta LAR s Auto-injector mentioned as an advantage by s Payers see late market entrance as a potential disadvantage Once weekly has a tremendous compliance effect." - Once weekly dosing only may be an advantage but I would like to see study results on compliance for this patient population. -Payer 75% of patients at HbA1ctarget much better than before. -Payer I don t see a difference between [Byetta LAR] and [RO507]. -Payer Final Report_Roche Diabetes February 29,

13 Non-inferiority to SUs may make a psychological difference to payers s regard HbA1c non-inferiority to glimepiride as less of an issue. Payers are also more conservative than s about the potential advantage in HbA1c superiority vs. Lantus. vs. glimepiride: Non-inferiority instead of HbA1c reduction superiority vs. Lantus: HbA1c reduction superiority instead of non-inferiority Changes perception Doesn t change perception Changes perception Doesn t change perception Being non-inferior to sulfonylureas might decrease the likelihood of RO507 being prescribed as the first add-on to metformin For s, superiority with regard to weight gain and hypoglycemia is even more important than superior HbA1c reduction as these are the main concerns with glimepiride. Non-inferiority in HbA1c reduction may be a psychological disadvantage for payers since it shows that the new product is not better than current treatment options One of payers concerns is that HbA1c superiority of an antidiabetic agent can be a function of dose increases. The trial design would need to reflect realistic doses to alleviate this concern For s, HbA1c superiority, together with the GLP-1 weight loss, would demonstrate a significant advantage over Lantus s expect to initiate treatment with RO507 earlier with this data Final Report_Roche Diabetes February 29,

14 Additional data may help to justify RO507's price, but not 2.50 ex manu Superiority in the GLP-1 analog class will be a driver for RO507 but with limited direct influence on the price. Long-term outcome data may be a key selling point but it counts only if published. Justifies 2.50 ex manu / day? Head-to-head trial vs. other GLP-1 analogs Ongoing longterm CV outcome studies s do not expect surprising clinical findings from head-to-head trials within the GLP-1 class. Therefore, they saw very limited or no change in pricing opportunities based on these trials For payers, such trials are useful for marketing that is targeted at physicians. However, they do not expect the price to be affected since neither Byetta nor the other GLP-1 analogs are considered the T2D gold standard However, intra-class comparisons may help to differentiate RO507 from the other GLP-1s to avoid grouping into one single FRP group s expect long-term outcome data to be crucial for the acceptance of wider usage with the potential to become the future standard of care In order to win the long-term race against DPP-IV inhibitors and TZDs, these long-term studies are a must Payers appreciate the effort to conduct outcome trials. Trials which have not been initiated yet are of no value for payers However, only published trial data will have an actual effect on payers' perception of RO507 "These long-term studies are a must. TZDs could not hold their promises." - Payer "This price level cannot be justified by any additional data." -Payer Final Report_Roche Diabetes February 29,

15 Expectations for clearly higher therapy cost are ambitious Payers agree that prices established by TZDs and DPP-IVs are an upper threshold for new therapies. A compelling clinical profile is required to overcome this. Value Drivers for RO507? Weight reduction can even be a threat if marketed as anti-obesity drug." - Payer Potential value drivers to justify prices of 2.20 ex manu and higher HbA1c overall average reduction: Still the primary value driver, especially for payers. Serves as a value driver only if less expensive therapy options are clearly outperformed (e.g. HbA1c reduction > 2.5%). Economic considerations: Savings on bloodglucose test strips demonstrated in a prospective study could justify a higher price (around 2.00) than e.g. Lantus. HbA1c-level share of patients treated to target: Payers would appreciate a very low risk for treatment failures, e.g. 90% of patients receiving target values. Weight loss: Endpoint gaining acceptance among payers as well, but not yet seen as a major value driver. Beta-cell protection: Potential value driver in the future. However, payers still doubt that improved beta-cell survival can be shown. Payers' arguments against higher prices in T2D Budget impact: Payers are concerned about growing prevalence and T2D treatment cost. As T2D is also a life-long therapy, payers consider the T2D market financially attractive for pharmaceutical companies even if products are priced at reasonable levels. Current T2D therapy price level: Payers consider prices of TZDs and DPP-IVs as pushing the limit. Improved clinical performance could therefore justify switching to a new therapy rather than higher therapy costs. In addition, Lantus (which is priced at the same price level as TZDs and DPP-IV) is perceived to offer higher value. Short-acting insulin-analog case: List prices of insulin analogs are around 30% above human insulin, which triggered reimbursement exclusion. Even higher cost increases for other T2D therapies would require very compelling clinical benefits to avoid a decision similar to Byetta BID. Final Report_Roche Diabetes February 29,

16 Appendix Final Report_Roche Diabetes February 29,

17 Product Profile Byetta BID Approved Therapeutic Indication Byetta is indicated for the treatment of T2 diabetes in combination with oral antidiabetics MET, SU or MET+SU in patients who have not achieved adequate glycemic control on maximally tolerated doses of these antidiabetic therapies. Market introduction: 2007 Efficacy Impact on HbA1c Byetta BID -0.8% from baseline (8.2%) at 30 weeks Patients reaching HbA1c goal 46% of patients reach HbA1c < 7% Weight Loss* 2.5 kg loss from baseline mean body weight of 101 kg Dosing and Administration Dosing Delivery Device Byetta BID Twice daily, subcutaneous injection for T2 Diabetes Reusable pen with a 29-gauge visible needle, replace needles, 6 steps Safety/Tolerability GI Side Effects (transient, mild-mod) Immunogenic Risk Byetta BID Nausea: 44% of patients (26%*) Vomiting: 13% of patients (9%*) Diarrhea: 13% of patients (7%*) Medium to high * Placebo-adjusted SU: sulfonylurea; TZD: thiazolidinedione; MET: metformin; T2: Type 2; kg: kilogram. Final Report_Roche Diabetes February 29,

18 Product Profile Product A [Liraglutide] (1/2) Expected Therapeutic Indication Product A is indicated for the treatment of T2 diabetes: as monotherapy in patients inadequately controlled by diet and exercise; in combination with oral antidiabetics (including MET, SU, MET+SU, and MET+TZD) in patients who have not achieved adequate glycemic control on maximally tolerated doses of these antidiabetic therapies. Expected Market introduction: 2009 Efficacy Impact on HbA1c Product A Between -1% and -1.5% from baseline (<8.5%) at 30 weeks Patients reaching HbA1c goal 40-55% of patients reach HbA1c < 7% Weight Loss* 2 kg loss from baseline mean body weight of kg* Dosing and Administration Dosing Delivery Device Safety/Tolerability GI Side Effects (transient, mild-mod) Immunogenic Risk Product A Once daily, subcutaneous injection for T2 Diabetes Reusable pen with a 32-gauge visible needle, replace needles, 6 steps Nausea: 5-20% of patients Vomiting: 3% of patients Diarrhea: 9% of patients Low Product A * Placebo-adjusted SU: sulfonylurea; TZD: thiazolidinedione; MET: metformin; T2: Type 2; kg: kilogram. Final Report_Roche Diabetes February 29,

19 Product Profile Product A [Liraglutide] (2/2) Clinical study design Monotherapy: Product A vs. SU Dual therapy: Add-on to SU: Product A vs. rosiglitazone & vs. placebo Dual therapy: Add-on to met: Product A vs. glimepiride & vs. placebo Triple therapy: Add-on to TZD+met: Product A vs. placebo Triple therapy: Add-on to met+su: Product A vs. Lantus & vs. placebo Product A vs. Byetta BID Product A Statistical superiority to glimepiride in HbA1c reduction Statistical superiority to rosiglitazone in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Non-inferiority to glimepiride in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Non-inferiority to Lantus in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Statistical superiority to Byetta BID in HbA1c reduction Potential additional information available post-launch (Phase 3B/4): Future indication in non-diabetic obesity * Placebo-adjusted SU: sulfonylurea; TZD: thiazolidinedione; MET: metformin; T2: Type 2; kg: kilogram. Final Report_Roche Diabetes February 29,

20 Product Profile Product B [Byetta LAR] (1/2) Expected Therapeutic Indication Product B is indicated for the treatment of T2 diabetes: as monotherapy in patients inadequately controlled by diet and exercise; in combination with oral antidiabetics (including MET, SU or MET+SU) in patients who have not achieved adequate glycemic control on maximally tolerated doses of these antidiabetic therapies. Expected Market introduction: 2011 Efficacy Impact on HbA1c Product B Between -1.7% and -1.9% from baseline (8.2%) at 30 weeks Patients reaching HbA1c goal 75% of patients reach HbA1c < 7% Weight Loss* kg loss from baseline mean body weight of 110 kg Dosing and Administration Dosing Delivery Device Product B Once weekly, subcutaneous injection for T2 Diabetes Disposable syringe with 23-gauge visible needle, 6 steps with reconstitution Safety/Tolerability GI Side Effects (transient, mild-mod) Immunogenic Risk Product B Nausea: 30% of patients (20%*) Vomiting: 13% of patients (9%*) Diarrhea: 13% of patients (7%*) Medium to high * Placebo-adjusted SU: sulfonylurea; TZD: thiazolidinedione; MET: metformin; T2: Type 2; kg: kilogram. Final Report_Roche Diabetes February 29,

21 Product Profile Product B [Byetta LAR] (2/2) Clinical study design Product B vs. Byetta BID Product B Statistical superiority to Byetta BID in HbA1c reduction Potential additional information available post- launch (Phase 3B/4): Head-to-head study demonstrating statistical superiority in HbA1c reduction to pioglitazone Head-to-head study demonstrating statistical superiority in HbA1c reduction to Januvia Head-to-head study demonstrating statistical superiority in HbA1c reduction to insulin glargine As monotherapy, head-to-head study demonstrating statistical superiority in HbA1c reduction to metformin * Placebo-adjusted SU: sulfonylurea; TZD: thiazolidinedione; MET: metformin; T2: Type 2; kg: kilogram. Final Report_Roche Diabetes February 29,

22 Product Profile Product C [RO507] (1/2) Expected Therapeutic Indication Product C is indicated for the treatment of T2 diabetes in combination with oral antidiabetics (including MET, TZD, and MET+TZD) in patients who have not achieved adequate glycemic control on maximally tolerated doses of these antidiabetic therapies. Expected Market introduction: 2012 Efficacy Impact on HbA1c Product C Between -1.7% and -1.9% from baseline (8-8.5%) at 30 wks Patients reaching HbA1c goal 70-75% of patients reach HbA1c < 7% Weight Loss* kg loss from baseline body weight of kg Dosing and Administration Dosing Delivery device Safety/Tolerability GI Side Effects (transient, mild-mod) Immunogenic Risk Product C Once weekly, subcutaneous injection for Type 2 Diabetes. Single use, fixed dosed, two-steps auto-injector that does not require priming No needle manipulation or reconstitution 29-gauge, hidden needle Nausea: 25%* of patients Vomiting: 5%* of patients Diarrhea: 5%* of patients Low Product C * Placebo-adjusted SU: sulfonylurea; TZD: thiazolidinedione; MET: metformin; T2: Type 2; kg: kilogram. Final Report_Roche Diabetes February 29,

23 Product Profile Product C [RO507] (2/2) Clinical study design Monotherapy: Product C vs. placebo Dual therapy: Add-on to met: Product C vs. SU & vs. placebo Dual therapy: Add-on to met: Product C vs. Januvia & vs. placebo Dual & triple therapy: Add-on to TZD+/-met: Product C vs. placebo Triple therapy: Add-on to met: Product C vs. Lantus & vs. placebo Product C vs. Byetta BID Product C Statistical superiority to placebo in HbA1c reduction Statistical superiority to glimepiride in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Statistical superiority to Januvia in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Non-inferiority to Lantus in HbA1c reduction Statistical superiority to placebo in HbA1c reduction Statistical superiority to Byetta BID in HbA1c reduction Additional information available 1-2 years after launch: patient preference is clearly in favor of Product C s device (over Product B s device) mechanistic studies document the benefit of Product C on glucose metabolism and beta cell, weight loss, cardiovascular outcomes in preclinical studies effects of Product C on pancreas and beta cell preservation delay/in DM onset are demonstrated. * Placebo-adjusted SU: sulfonylurea; TZD: thiazolidinedione; MET: metformin; T2: Type 2; kg: kilogram. Final Report_Roche Diabetes February 29,

24 Price references Drug Active ingredient Defined Daily Dosage (ATC-index) Public Therapy Cost per day (AVP) Generic metformin Metformin 2g 0.25 Amaryl Glimepiride 2mg 0.35 Actos Pioglitazone 30 mg 1.98 Avandia Rosiglitazone 6 mg 1.97 Avandamet Rosiglitazone/ metformin 6 mg / 1,500 mg 2.36 Galvus Vildagliptin 100 mg 1.96 Januvia Sitaglitpin 100 mg 1.96 Huminsulin Basal Human insulin 40 Units 1.21 Lantus Insulin analog 40 Units 1.96 Byetta Exenatide 15 μg 4.05 Source: ATC-index (Galvus DDD based on EMEA report, Avandamet DDD based on mean of label dosage). Avandia price based on 1.5*4mg tablet, Avandamet price based on 1.5*4mg/1000mg tablet, Insulin prices based on 0.8*100 units, Byetta 1*5μg + 1*10μg per day. Based on N2 packages, Huminsulin Basal Cartridges for Pen, Lantus Cartridges for OptiPen. Final Report_Roche Diabetes February 29,