Approvals and advisory committee recommendations last week by the US Food and Drug Administration and the European Medicines Agency have put the markets for hepatitis C and anti-cholesterol drugs into greater play with several blockbluster contenders by AbbVie, Merck & Co., Sanofi, and Amgen in the mix. So how do these newly approved or drug candidates fit into the current and future market? DCAT Value Chain Insights (VCI) takes an inside look.

Competition in the anti-cholesterol market is intensifying as two new biologics, respectively by Amgen and Sanofi/Regeneron Pharmaceuticals, have reached the finish line for regulatory approval and commercialization. Meanwhile, AbbVie’s Technivie, the second oral hepatitis C drug by AbbVie to be approved by the US Food and Drug Administration (FDA), is the latest entry in the hepatitis C market, which is led by Gilead Sciences’ Sovaldi (sofosbuvir), one of the industry’s top-selling drugs in 2014, as Merck & Co.’s combination hepatitis C therapy moves to regulatory review. DCAT Value Chain Insights (VCI) examines the market implications.

Biologics blockbusters enter the anti-cholesterol market
Last week was a busy one for the anti-cholesterol market with regulatory approvals and recommendations for approval for Amgen and Sanofi/Regeneron. The European Commission granted marketing authorization for Amgen’s Repatha (evolocumab), a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor 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 inhibitor, a potential blockbluster class of drugs, for treating cholesterol. Repatha, developed by Amgen scientists, is under regulatory review by the US Food and Drug Administration (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.

Meanwhile, 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 (CHMP) also adopted a positive opinion for the marketing authorization of Praluent, recommending its approval for use in certain adult patients with hypercholesterolemia. The European Commission is expected to make a final decision on the marketing authorization application for Praluent in the European Union in late September.

Sanofi/Regeneron are in a competition to market for its PCSK9 inhibitor with Amgen and its PCSK9 inhibitor, Amgen’s Repatha. Pfizer also has a late-stage PCSK9 inhibitor, bococizumab, which is now in a Phase III clinical trial program. A a recent Thomson Reuters analysis pegs these drugs as potential blockbusters. Based on estimates for 2019 sales, the 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.

Competition in the hepatitis C market
Drugs to treat hepatitis C are another hot market area. Last week, the FDA approved AbbVie’s Technivie (ombitasvir, paritaprevir and ritonavir) for use in combination with ribavirin for treating hepatitis C virus (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.

In 2013, Gilead Sciences received FDA approval for Sovaldi (sofosbuvir) to HCV infection, the first drug oral drug to treat certain types of HCV infection without the need for co-administration of interferon as a component of a combination antiviral treatmen regimen. Solvadi was approved to treat subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Sovaldi was Gilead’s top-selling drug in 2014 and was 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.Gilead’s Harvoni, an oral combination of sofosbuvir and ledipasvir for treating HCV, was approved and launched in the US in October 2014.

The competition in the HCV market is strong. AbbVie’s Viekira Pak (veruprevir, ritonavir, ombitasvir, and dasabuvir) is an all oral HCV regime with projected 2019 sales of $2.5 billion, which will compete against Gilead Science’s Harvoni (combination of sofosbuvir and ledipasvir), according to a recentThomson Reuters analysis. Also in that space for 2015 will be Merck & Co.’s HCV combination of grazoprevir and elbasivr, with  projected 2019 sales of $2.167 billion expected in 2019.

Last week, the 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 chronic hepatitis C (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 Committee for Medicinal Products for Human Use (CHMP) 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.

Last week, the FDA approved Bristol-Myers Squibb’s Daklinza (daclatasvir) for use with sofosbuvir to treat hepatitis C virus (HCV) genotype 3 infections. Daklinza is the first drug that has demonstrated safety and efficacy to treat genotype 3 HCV infections without the need for co-administration of interferon or ribavirin, two FDA-approved drugs also used to treat HCV infection, according to the FDA. Genotype 3 is estimated to affect 12% of chronic HCV patients in the US and is the second most common hepatitis C genotype globally after genotype 1.

Daklinza is an inhibitor of NS5A with dual modes of anti-viral activity that inhibits both RNA replication and virion assembly. In in vitro studies, Daklinza has shown anti-viral activity across genotypes 1-6, with EC50 values from picomolar to low nanomolar against wild type replicons. Daklinza will be available and begin shipping within a week.

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.