Potential Blockblusters: New Market Entries on the Radar


From DCAT Value Chain Insights (VCI)

By Patricia Van Arnum posted 08-03-2015 09:49

  

What are the blockbusters of the future? A recent industry analysis points to the leading contenders from late-stage or newly approved drugs.

This year has seen the market entry of several drugs pegged as future blockbusters. So what new molecular entities are on the market’s radar and how do they fit in the competitive landscape? DCAT Value Chain Insights (VCI) takes an inside look.

The commercial success of a drug is difficult to predict, but a recent analysis by Thomson Reuters points to 11 drugs, which are projected to be blockbuster drugs (defined as drugs with sales of $1 billion or more) by 2019. Table I outlines these drugs, which include products from the large pharmaceutical companies, such as AbbVie, Amgen, Bristol-Myers Squibb, Merck & Co, Novartis, Pfizer, and Sanofi, as well as products from Vertex Pharmaceuticals, Otsuka Pharmaceutical, and Lundbeck.

Drugs to watch for in 2015
Compared with 2014, the Thomson Reuters analysis points out there are more potential blockbusters expected to enter the market in 2015 (see Table I ). The majority of them are forecast to have 2019 sales of between $1 billion and $3 billion although three drugs are projected to exceed these revenue targets by 2019: Bristol-Myers Squibb’s anti-cancer drug for treating melonoma, Opdivo (nivolumab) at nearly $5.7 billion; Regeneron Pharmaceuticals and Sanofi’s Praluent (alirocumab) for treating hypercholesterolemia at $4.4 billion; and Novartis’ LCZ-696, a drug for treating chronic heart failure, at $3.7 billion. LCZ-696, which is an angiotensin receptor-neprilysin inhibitor, consists of Novartis’ angiotensin receptor blocker, Diovan (valsartan), and a new compound, sacubitiril, a neprilysin inhibitor. This year’s other potential blockbuster entrants (see Table I ) are: Pfizer’s Ibrance (palbociclib) for treating breast cancer; Vertex Pharmaceuticals' combination therapy of lumacaftor and ivacaftor for treating cystic fibrosis; AbbVie’s Vierkira Pak (veruprevir, ritonavir, ombitasvir, and dasabuvir) for treating hepatitis C virus (HCV) infection; Amgen’s and Astellas Pharma’s evolucumab for treating hypercholesterol/hyperlipidemia; Merck & Co.’s Gardasil 9 vaccine against human papillomavirus infection; Otuska Pharmaceutical’s and Lundbeck’s brexpiprazole for treating schizophrenia and depression; Sanofi’s Toujeo (a new formulation for insulin glargine) for treating diabetes; and Novartis’ Cosentyx (secukinumab) for treating psoriasis and psoriatic arthritis.

Table I: Potential Blockbuster Entrants in 2015 Based on 2019 Projected Sales
Drug Disease Pharmaceutical Company 2019 Forecast sales (US $billions)
Opdivo (nivolumab) Melanoma Bristol-Myers Squibb $5.684 bn
Praluent (alirocumab) Hypercholesterolemia Regeneron Pharmaceuticals and Sanofi $4.414 bn
LCZ-696 (sacubitril and valsartan) Chronic heart failure Novartis $3.731 bn
Ibrance (palbociclib) Breast cancer Pfizer $2.756 bn
lumacaftor and ivacaltor Cystic fibrosis Vertex Pharmaceuticals $2.737 bn
Viekira Pak (veruprevir, ritonavir, ombitasvir, and dasabuvir) Hepatitis C AbbVie $2.500 bn
evalocumab Hypercholesterolemia/hyperlipidemia Amgen and Astellas Pharma $1.862 bn
Gardasil 9 Vaccine against human papillomavirus infection Merck & Co. $1.637 bn
brexpiprazole Schizophrenia and depression Otsuka and Lundbeck $1.353 bn
Toujeo (new formulation insulin glargine) Diabetes Sanofi $1.256 bn
Cosentyx (secukinumab) Psoriasis and psoriatic arthritis Novartis $1.082 bn
*Analysis based on data through early February 2015.

Source: Thomson Reuters (Cortellis Competitive Intelligence)

Key trends
Several key trends are noted in the Thomson Reuters analysis, which include the rise of immune-oncology approaches for treating cancer, innovation in treating cholesterol, the entry of a first-in-class drug to treat chronic heart failure, and the entry of additional all-oral regimes for treating HCV injection. Within the immune-oncology space, the Thomson Reuters analysis points to a key battle between two new melanoma drugs, Bristol-Myers Squibb’s Opdivo (nivolumab) and Merck & Co,’s Keytruda (pembrolizumab). Sanofi’s and Regeneron’s Praluent (alirocumab) and Amgen’s and Astellas Pharma’s evolocumab are two top contenders in the anti-cholesterol market, and Novarti’s LCZ-696 is a new entry for treating chronic heart failure. In the HCV market, top contenders are Gilead (with Sovaldi (sofosbuvir) and Harvoni (combination of sofosbuvir and ledipasvir), AbbVie with Vierkira Pak (veruprevir, ritonavir, ombitasvir, and dasabuvir), and Merck & Co. with its HCV combination of grazoprevir and elbasvir, for which a regulatory filing was recently made.

Tracking the potential blockbusters

Oncology market. In the oncology market, the potential of Bristol-Myers Squibb’s (nivolumab) is strong. The drug was first approved in Japan in September 2014, but it is the US market, where the potential is high, according to the Thomson Reuters analysis. The drug was approved in the US in late December 2014 for treating unresectable or metastatic melanoma and was launched in February 2015. In the US, Opdivo is approved for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. In March 2015, Opdivo received its second US Food and Drug Administration (FDA) approval for the treatment of patients with metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy. Opdivo was first approved in Japan in July 2014 for treating unresectable melanoma.

In June 2015, the European Commission (EC) approved Opdivo for treating advanced (unresectable or metastatic) melanoma in adults, regardless of BRAF status. The EC later approved Bristol-Myers Squibb's Nivolumab BMS (nivolumab) for treating locally advanced or metastatic squamous non-small (SQ) cell lung cancer (NSCLC) after prior chemotherapy. In the European Union, Bristol-Myers Squibb submitted two separate marketing authorization applications, one in advanced melanoma under the tradename Opdivo and one for SQ NSCLC under the Nivolumab BMS tradename in order to accelerate availability of nivolumab in both indications. The goal is to have these two marketing authorizations “reconciled” into a single marketing authorization, under the Opdivo brand name toward the end 2015. 2019 projected sales of Opdivo are at $5.684 billion (see Table I), competing against Merck & Co,’s Keytruda (pembrolizumab), which has 2019 projected sales of $3.466 billion, according to the Thomson Reuters analysis.

Keytruda was approved in the US in 2014 for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. In July 2015, the EC  approved Keytruda for treating advanced (unresectable or metastatic) melanoma in adults. Merck also received FDA’s Breakthrough Therapy Designation for Keytruda for treating advanced NSCLC. In June 2015, the FDA accepted Merck's supplemental biologics license application (sBLA) for Keytruda for treating advanced NSCLC that has progressed on or after platinum-containing chemotherapy and an FDA-approved therapy for EGFR or ALK genomic tumor aberrations, if present. The FDA granted priority review with a target action, date of October 2, 2015; the sBLA will be reviewed under the FDA’s Accelerated Approval program.

HCV market. The competition in the HCV market is also strong. AbbVie’s Viekira Pak (veruprevir, ritonavir, ombitasvir, and dasabuvir) is an all oral HCV regime with projected 2019 sales of $2.5 billion (see Table 1 ), which will compete against Gilead Science’s Harvoni (combination of sofosbuvir and ledipasvir), with 2019 projected sales of $6.697 billion, according to the Thomson Reuters analysis. Also in that space for 2015 will be Merck & Co.’s HCV combination of grazoprevir and elbasivr, with a US filing made in 2015 and first sales in 2016 and projected 2019 sales of $2.167 billion expected in 2019. These drugs will compete against an already market leader in the HCV market, Sovaldi, Gilead’s top-selling drug in 2014 and one of the industry’s top-selling drugs with 2014 sales of $10.28 billion, making it one of the most successful first-year launches for a new molecular entity. Sovaldi, which was approved by the FDA in December 2013 and in the European Union in January 2014, was the first drug that demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon, which is administered by injection. Sovaldi is a nucleotide analog inhibitor that blocks a specific protein needed by the hepatitis C virus to replicate, and that mechanism of action was considered an important advancement as well as the ability to administer the drug orally. The drug is forecasted to have sales of $10.5 billion in 2015, dropping slightly, and rising to $12.0 billion in 2019. Gilead’s Harvoni, an oral combination of sofosbuvir and ledipasvir for treating HCV, was approved and launched in the US in October 2014.

In terms of other potential blockbusters in the HCV market, in July 2015, the European Medicines Agency (EMA) accepted for review Merck's marketing authorization application (MAA) for grazoprevir/elbasvir (100 mg/50 mg), an investigational, once-daily, single-tablet combination therapy for treating adult patients with HCV genotypes (GT) 1, 3, 4 or 6 infection. The EMA will initiate review of the MAA under accelerated assessment timelines. The EMA’s accelerated assessment is available for products that respond to unmet medical needs or represent a significant improvement over current treatment options within a major public health interest, such as the treatment of chronic HCV infection. The EMA's Committee for Medicinal Products for Human Use will continue to evaluate the accelerated assessment status throughout the MAA evaluation process. Merck submitted a new drug application for grazoprevir/elbasvir (100 mg/50 mg) to the FDA in May 2015 for treating chronic HCV GT1, 4 or 6 infection, and is submitting additional license applications in other markets by the end of 2015. Grazoprevir/elbasvir is Merck’s investigational, once-daily, single-tablet combination therapy consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being evaluated in multiple HCV genotypes, including patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis, and in those on opiate substitution therapy. In April 2015, the FDA granted Breakthrough Therapy designation status for grazoprevir/elbasvir for treating patients with chronic HCV GT1 with end-stage renal disease on hemodialysis, and Breakthrough Therapy designation status for grazoprevir/elbasvir for treating patients infected with chronic HCV GT4. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

There are other recent entrants in the HCV market. In July 2015, the FDA approved AbbVie's Technivie (ombitasvir, paritaprevir and ritonavir) for use in combination with ribavirin for HCV genotype 4 infections in patients without scarring and poor liver function (cirrhosis). Technivie in combination with ribavirin was approved to treat genotype 4 HCV infections without the need for co-administration of interferon, an FDA-approved drug also used to treat HCV infection. Technivie is the second oral hepatitis C drug by AbbVie to be approved by the FDA. In 2014,the FDA approved AbbVie's Viekira Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets) to treat patients with HCV genotype 1 infection, including those with a cirrhosis.

Also in July 2015, the FDA approved Bristol-Myers Squibb's Daklinza (daclatasvir) for use with sofosbuvir to treat hepatitis C virus (HCV) genotype 3 infections. Daklinza is an inhibitor of NS5A with dual modes of anti-viral activity that inhibits both RNA replication and virion assembly. In July 2014, Japan became the first countr approve the use of a daclatasvir-based regimen for the treatment of chronic HCV. Since then, daclatasvir-based regimens have been approved across Europe, as well as numerous other countries in Central and South America, the Middle East, and the A hesia-Pacific region.

Anti-cholesterol market. The anti-cholesterol market has seen two potential blockbusters approved this year: Sanofi's/Regeneron's Praluent (alirocumab) and Amgen's/Astellas Pharma Repatha (evolocumab), two new drugs with a new mechanism of action, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, for treating high cholesteroel. Based on estimates for 2019 sales, the Thomson Reuters analysis puts potential revenues at Regeneron Pharmaceuticals and Sanofi’s Praluent (alirocumab) at $4.4 billion, and Amgen’s/Astellas' evolocumab at nearly $1.9 billion by 2019.

In July 2015, the EC granted marketing authorization for Amgen's Repatha (evolocumab) for treating uncontrolled cholesterol in patients that require additional intensive low-density lipoprotein cholesterol (LDL-C) reduction. Repatha is a human monoclonal antibody that inhibits PCSK9, a protein that reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood. Approval from the EC grants a centralized marketing authorization with unified labeling in the 28 countries that are members of the EU. Norway, Iceland, and Liechtenstein, as members of the European Economic Area (EEA), take corresponding decisions on the basis of the decision of the EC. The EC approval marked the first regulatory approval for a PCSK9 Repatha, developed by Amgen scientists, is under regulatory review by the FDA with a target action date of August 27, 2015. Amgen is partnered with Astellas Pharma for Repatha in Japan as part of a multi-drug collaboration the companies formed in 2013. The long-term collaboration focuses on the co-development and co-commercialization in Japan of five Amgen pipeline medicines (which included the now approved Repatha) and also created a Tokyo-based joint venture company, Amgen Astellas BioPharma KK.

Also in July 2015, Sanofi/Regeneron Pharmaceuticals received FDA approval for their PCKS9 inhibitor,Praluent (alirocumab) injection. Praluent is approved for use in addition to diet and maximally tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH) or patients with clinical atherosclerotic cardiovascular disease such as heart attacks or strokes, who require additional lowering of LDL cholesterol. HeFH is an inherited condition that causes high levels of LDL cholesterol. The European Medicine Agency's (EMA's) Committee for Medicinal Products for Human Use also adopted a positive opinion for the marketing authorization of Praluent, recommending its approval for use in certain adult patients with hypercholesterolemia. The EC is expected to make a final decision on the marketing authorization application for Praluent in the European Union in late September.

Other areasOther potential blockbusters have been approved thus far in 2015. In July 2015, the FDA approved Novartis' Entresto (sacubitril/valsartan) for treating heart failure with reduced ejection fraction. The drug has been shown to reduce the rate of cardiovascular death and hospitalization related to heart failure. It is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin receptor blocker. Novartis has high hopes for Entresto, pegging it as one of the key drugs among its new product candidates. TheThomson Reuters analysis estimates 2019 sales for Entresto at $3.7 billion, and Novartis estimates offer possible peak sales in excess of $5 billion for the reduced ejection fraction indication on global basis. Entresto is currently undergoing review by health authorities around the world, including in Canada, Switzerland, and the European Union, where it is under accelerated review. Entresto is an angiotensin receptor neprilysin inhibitor that reduces the strain on the failing heart. A twice-a-day tablet, it acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful system, the renin-angiotensin-aldosterone system (RAAS).

Also in July 2015, the FDA approved Rexulti (brexpiprazole) tablets, by Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S to treat adults with schizophrenia and as an add-on treatment to an antidepressant medication to treat adults with major depressive disorder (MDD). Rexulti was discovered by Otsuka and co-developed with Lundbeck. It will be co-marketed by the two companies and is expected to become available to patients in the United States in early August 2015. The recent Thomson Reuters analysis offered 2019 sales estimates of the drug at $1.35 billion.

In February 2015, Pfizer received FDA approval for Ibrance (palbociclib), a small molecule to treat advanced (metastatic) breast cancer. The Thomson Reuters analysis estimated 2019 sales of $2.756 billion. Vertex Pharmaceuticals received FDA approval for Orkambi (lumacaftor 200 mg/ivacaftor 125 mg) for treating cystic fibrosis (CF) directed at treating the cause of the disease in people who have two copies of a specific mutatio. The approved to treat CF in patients 12 years and older, who have the F508del mutation, which causes the production of an abnormal protein that disrupts how water and chloride are transported in the body. The Thomson Reuters estimates 2019 sales of $2.7 billion.

Also approved in 2015 was Sanofi's Touejo (insulin glargine [rDNA origin]. a basal insulin for treating Type 1 and Type 2 diabetes mellitus. Toujeo is a next-generation, once-daily basal insulin based on a broadly used molecule (insulin glargine), which is the active ingredient in Sanofi's best-selling product, Lantus. Lantus had 2014 sales of EUR 6.344 billion ($7.180 billion) which faced patent expiry, effective in February 2015 in the US and in May 2015 in the European Union. Touejo's sales are estimated at nearly $1.3 billion .Touejo was approved in the US in February 2015 and the European Union in April 2015 and was recently approved in Japan.

Another potential blockbuster is Novartis' Cosentyx (secukinumab), a drug to treat adults with moderate-to-severe plaque psoriasis, which was approved in the US and the European Union earlier this year. Secukinumab is an antibody that binds to a protein (interleukin (IL)-17A), which is involved in inflammation. By binding to IL-17A, secukinumab prevents it from binding to its receptor, and inhibits its ability to trigger the inflammatory response that plays a role in the development of plaque psoriasis. Cosentyx is administered as an injection under the skin. It is intended for patients who are candidates for systemic therapy (treatment using substances that travel through the bloodstream, after being taken by mouth or injected), phototherapy (ultraviolet light treatment), or a combination of both. Cosentyx is being evaluated for treating psoriatic arthritis and ankylosing spondylitis with regulatory applications planned for 2015.

Evaluating 2014 blockbuster entrants
In addition to Gilead's Sovaldi, two drugs from 2014 that were identified as potential blockbusters from the Thomson Reuters analysis and are still on track to achieve blockbuster status by 2019: GlaxoSmithKline’s and Theravance’s Anoro Elipta (umeclidinium plus vilanterol) and Gilead Sciences’ Zydelig (idelalisib) for treating chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin’s lymphomas, such as follicular B-cell non Hodgkin lymphoma (FL) and small lymphocytic lymphoma (SLL). 

GlaxoSmithKline’s and Theravance Anoro Elipta entered the US market for treating chronic obstructive pulmonary disease in April 2014, was launched in the European Union in July 2014, and in Japan in September 2014. Projected 2019 sales are approximately $1.6 billion, which would exceed the developers’ previous blockbuster, Relovair (fluticasone furoate plus vilanterol trifenatate), which is projected at $1.176 billion in 2019.

Another drug from 2014 still on track for blockbuster status by 2019 s Gilead’s anticancer drug Zydelig, which was approved and launched in the US in July 2014 and received approval for CLL and FL in September 2014. Current forecasts show sales of approximately $649 million in 2017 and increasing to $1.041 bllion by 2019.

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