IV. Sales of Entresto® rising steadily upon the Class I recommendation by the European and American heart failure guideline

Novartis announced on May 21, 2016 that the Guideline for the Management of Heart Failure recently updated by the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) and European Society of Cardiology (ESC) gave a Class I recommendation for Entresto® in treating heart failure.

The guideline updated by ACC/AHA/HFSA recommended "Entresto®+ β-receptor blocker+ aldosterone antagonist" as the standard therapy for patients with heart failure and reduced ejection fraction, to serve as an alternative to the conventional angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs for heart failure. The guideline of ACC/AHA/HFSA recommended patients with mild to moderate heart failure who are tolerant to ACE or ARB to change to use Entresto®.

In the Europe, ESC also updated the Guidelines for the diagnosis and treatment of acute and chronic heart failure based on the results of PARADIGM-HF study, and recommended patients with mild to moderate heart failure who have stable condition but poor blood pressure control, and are tolerant to ACE or ARB to change to use Entresto® for treatment.

Sales of Entresto® rose with the recommendation by clinical guidelines: the sales of Entresto® in 2017 Q2 reached USD 110 million, according to the quarterly report of Novartis.

Fig. 1 Sales Situation of Entresto® in Recent Years

In addition, according to Elevatepharm’s forecast on Entresto® sales, the sales of Entresto® will reach USD 4.881 billion in 2022, hopefully to become the top 1 on the heart disease drug market.

Fig. 2 Elevatepharm’s Forecast on Sales of Entresto® in the Next 6 Years

V. Guess of price of Entresto® on the Chinese market

The guess of the market price of Entresto® is made mainly based on the daily treatment expense of the current gold standard regimen and the price situation of the new heart failure drug: Ivabradine Hydrochloride in China.

Calculation of the daily treatment expense of current gold standard regimen

Heart failure is mainly treated with drug combination. The daily treatment expense of the gold standard therapeutic regimen for patients is calculated according to the pharmaceutical product retail prices:

Recent Bid-winning Prices of Drugs in the Gold Standard Regimen for Heart Failure

Regimen 1: Enalapril and Metoprolol Succinate

Administration and dosage of Enalapril:

Initial dose: 2.5mg, twice a day, dose increased 1 time every other week, until the target dose of 10mg, twice a day;

Administration and dosage of Metoprolol Succinate:

Initial dose: 23.750mg, once a day, dose increased 1 time every other 2-4 weeks, until the target dose of 142.5mg-190.0mg, once a day;

According to the above administration and dosage of the two drugs, the daily treatment expense of every patient will be 0.727 *2+2.117*4=RMB 9.922 when two drugs reach the target dose.

Regimen 2: Enalapril and Candesartan

Administration and dosage of Candesartan:

Initial dose: 4mg, once a day, target dose: 32mg, once a day;

According to the above administration and dosage of the two drugs, the daily treatment expense of every patient will be 0. 727 *2+4.371*4=RMB 18.938 when two drugs reach the target dose.

Therefore, the daily treatment expense of the current gold standard treatment is RMB 9.93-18.94, and the monthly treatment expense is RMB 298-568.

The price of Ivabradine Hydrochloride is about RMB 6,300/year in China

The recommended initial dose of ENTRESTO is 49/51mg, twice a day. 2-4 weeks after patients are tolerant, ENTRESTO dose shall be doubled to the target maintenance dose of 97/103 mg, twice a day. With the above pricing factors taken together, the price of Entresto® on the Chinese market is guessed to be about RMB 30-36/day, RMB 900-1,080/month, and RMB 10,800-13,000/year.

VI. API patent application situation of Entresto® in China

API of Entresto® is the trisodium hemipentahydrate of valsartan and sacubitril. Novartis uses the complex+ co-crystallization technology according to the structural features of the two active ingredients. Looking back upon the R&D process, in fact, Novartis started to apply for the drug combination patent of ARNI dual targets or even multiple targets early in 2003, but did not publicize the compound of the two active ingredients of Entresto®, and until 2006, it started to conduct patent layout for the two active ingredients. In China, its API application has been granted, with publication No. CN101098689B, and filing date of November 8, 2006.

VII. Conclusion

As the first inhibitor of both angiotensin II receptor and neprilysin, Entresto® is different from the pure angiotensin II receptor: not only can Entresto® block RAAS through inhibiting angiotensin II receptor, it can also enhance in vivo protection mechanism and block receptors (angiotensin receptors) that participate in narrowing blood vessels through inhibiting neprilysin, therefore, Entresto® can act on 2 important pathways, have better efficacy than using ARB alone, and have good prospects in treating hypertension and heart failure. The clinical study results showed that the antihypertensive effect of Entresto® was better than that of valsartan, and Entresto® showed a good tolerance.

Entresto is better than Enalapril in improving the case fatality rate and hospitalization rate of heart failure patients, and the tolerance and safety of Entresto® are within acceptable limits. Entresto® can improve the prognosis of heart failure patients, and is a breakthrough in drug therapy in the heart failure area. Most of the present anti-heart-failure drugs treat patients through drug combination and shall be conducted dose adjustment, with poor patient compliance, however, Entresto® can inhibit both NEP and angiotensin receptor, is not required to treat patients in combination with ACE inhibitor or ARB drug, and requires taking twice every day. Entresto® dose not only facilitate patients’ use, it also improves patients’ compliance with the product.

Entresto® is a milestone revolution of the medical community in treating heart failure over the 25 years, with therapeutic effect better than the gold treatment standard. The Guideline for the Management of Heart Failure recently updated by the ACC/AHA/HFSA and ESC gave a Class I recommendation for Entresto® in treating heart failure.

The industry considers that the outstanding performance of Entresto® is one of the most important progressions achieved in the cardiology field. There will be no drug that can rival it in the cardiology field in the next few years. The global sales of Entresto® will exceed USD 4.5 billion in 2022, according to the forecast data of Elevatepharm.

By Biodiscover.com

Authored by Yunqing

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