Are the PCSK9 Inhibitors, Repatha and Praluent, the new Sovaldi?

The recent approval of Repatha (evolocumab) and Praluent (alirocumab), the PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors, by EMA and the FDA have provided a much-needed new treatment option for hypercholesterolaemia patients. But will the price, potential size of the patient population and payer’s recent experience with other novel treatments (e.g. Sovaldi) pose challenges to the commercial opportunity for these products?

Despite significant advances in treatments (e.g. statins) over the last 15 years, the majority of patients with a high cardiovascular risk still do not have their cholesterol levels under control. Based on the current clinical data, the PCSK9 inhibitors are a vital new treatment option for patients with high cholesterol. The PCSK9 inhibitors are monoclonal antibodies that require subcutaneous injection every two to four weeks (depending on the product). The use of PCSK9 inhibitors leads to a clinically significant reduction in LDL cholesterol levels of 54–77%, in patients that were already on cholesterol lowering medication. However, the impact on mortality and morbidity will only be conclusively known in 2018 when the cardiovascular outcomes studies read out.

The PCSK9 inhibitors have so far only be approved for limited patient populations (e.g. familial hypercholesterolaemia, approximately 600,000 patients in the US). However, the expectation is that the indication will be expanded to include those who are inadequately controlled on statins or at high risk of cardiovascular events. Estimates for this patient population range from 3.5–15 million patients, according to the Institute for Clinical and Economic Review (ICER), which recently reviewed these medications. The other issue is the length of therapy, as once patients are on cholesterol lowering medication, they typically remain on therapy for the rest of their lives.

The annual US treatment cost for Praluent is approximately $14,600, with Repatha costing $14,100. This price tag has caused concern with payers, with CVS Health warning that the costs could “eclipse the initial costs of Sovaldi”. In the EU, the annual cost for Repatha is substantially lower, ranging from $6,600–$8,220, depending on the market. Praluent has yet to receive EU marketing authorisation.

Payers are concerned about the budget impact of the PCSK9 inhibitors, as the potential yearly impact could hit $150 billion, if 15 million potential US patients are switched to these treatments. US payers will try to create competition between Praluent and Repatha with the aim of securing larger discounts, mirroring the same tactics that US payers used when Olysio launched into the HCV market. The level of discounts for Sovaldi increased from 22% in 2014 to 46% in 2015 once Olysio had launched. If such discounts are applied to the PCSK9 inhibitors in the US, suddenly the US price seems much more in line with the EU price level. However, the Institute for Clinical and Economic Review (ICER) has stated that even this price is too high and the PCSK9 inhibitors would need to undergo an 85% price decrease to ~$2,177 to have an annual value-based price that was cost-effective.

In the EU, it will be interesting to see how payers manage the potential budget impact and whether they resort to similar tactics as used for Sovaldi (i.e. share EU price data and threatening to implement joint procurement). EU payers have a broader range of tools to manage the PCSK9 inhibitors than in the US and some payers may try to delay reimbursement for the additional patient populations until mortality data are available. It will also be interesting to see whether NICE consider these products to be cost effective considering that their US counterpart, the ICER, does not.

Whilst there are strong parallels with Sovaldi’s launch (e.g. high price speciality drug; potentially large patient populations; significant budget impact; game changing levels of efficacy), there are differences. Sovaldi is a cure for HCV for the majority of patients, which will result in decreasing budget impact over time as the patient pool decreases. In contrast, the PCSK9 inhibitors are not a cure and patients will require life-long access to the treatment. Whilst the PCSK9 prices are six times lower than Sovaldi price, the budget impact will be significantly larger for the PCSK9 inhibitors, due to the high prevalence of cardiovascular disease and the increasing number of patient who will be on treatment. As such, it is expected that the PCSK9 inhibitor class will go on to be the top selling class of pharmaceuticals of all time.

The recent advances in medical science are producing a new wave of innovative, highly effective, speciality drugs, such as Sovaldi and the PCSK9 inhibitors in areas where there is high unmet need. The challenge payers are facing is the ever-increasing budget impact posed by these products. Payers have been responding with new and creative ways to try to ensure patient access, but at the end of the day, there is only a finite budget. It does appear that if prices continue to rise for breakthrough products, we must soon reach a tipping point where healthcare pharmaceutical funding mechanisms must change. The current price increases and funding implications seem unsustainable in the long run.