Blockbuster Watch: Key Market Entrants for 2016

What are the blockbusters of the future? A recent industry analysis points to the leading contenders anticipated for market launch in 2016.

The commercial success of a drug depends on a myriad of factors, so which drugs should be on the industry's radar for 2016? A recent analysis by Thomson Reuters points to seven drugs, slated to be launched in 2016, which are projected to reach sales of at least $1 billion by 2020. DCAT Value Chain Insights (VCI) examines the top contenders.

Potential blockbusters of the future
The Thomson Reuters analysis, Drugs to Watch 2016, points to seven drugs that are in late-stage development or recently approved and expected to be launched in 2016 with potential blockbuster status by 2020. For purposes of this analysis, blockbusters are defined as drugs with annual sales of at least $1 billion. Two of the seven drugs are expected to reach even greater heights, with two drugs projected to top $2 billion in annual sales by 2020. So what are the possible blockbusters of tomorrow?

Table I outlines these seven drugs, with five of the drugs coming from the major pharmaceutical companies or in partnership with the major pharmaceutical companies.

Table I: Potential Blockbuster Entrants in 2016 Based on 2020 Projected Sales
Drug Disease Pharmaceutical Company 2020 Forecast sales (US $billions)
Obeticholic acid Chronic liver disease, primarily primary biliary cirrhosis Intercept Pharmaceuticals and Sumitomo Dainippon Pharma $2.621 bn
Emtricitabine + tenofovir + alafenamide (F/TAF) HIV-1 infection Gilead Sciences and Japan Tobacco $2.006 bn
Tenofovir alafenamde + emtricitabine + rilpivirine (R/F/TAF) HIV-1 infection Gilead Sciences and Janssen R&D $1.572 bn
MK-5172A (grazoprevir + elbasvir) Hepatitic C virus (HCV) infection Merck & Co. $1.537 bn
Venetoclax Chronic lymphocytic leukemia AbbVie $1.477 bn
Nuplazid (pimavanserin) Parkinson's disease psychosis Acadia Pharmaceuticals $1.409 bn
Uptravi (selexipag) Pulmonary arterial hypertension Nippon Shinyaku Co and Actelion $1.268 bn
*Analysis based on data through early February 2016.

Source: Thomson Reuters (Cortellis Competitive Intelligence)

Leading the pack
On the top of the list is obeticholic acid (OCA) for treating chronic liver disease by Intercept Pharmaceuticals, a clinical-stage biopharmaceutical company focused on drugs to treat non-viral, progressive liver diseases, and licensed to Sumitomo Dainippon Pharma. The drug is a farnesoid X receptor agonist OCA as an oral treatment for chronic liver diseases. A rolling new drug application (NDA) submission was initiated in December 2014 for primary biliary cirrhosis (PBC), a rare liver disease that results from autoimmune destruction of the bile ducts in the liver. The drug is being indicated in PCB patients with inadequate response to ursodeoxycholic acid (UDCA) or as a monotherapy in adults unable to tolerate UDCA. The drug was granted priority review by the US Food and Drug Administration (FDA) in August 2015 with a Prescription Drug User Fee Act (PDUFA) date initially set for February 29, 2016, but which was later extended to May 29, 2016. A marketing authorization application (MAA) was accepted for review in the European Union in June 2015.

If approved, OCA could become the first new treatment for PBC in more than two decades, according to the Thomson Reuters analysis. Forecasts project sales of $29 million in 2016, rising to $2.621 billion in 2020. The only competing drug for PCB currently is UDCA, which is now generic.

Further upside for OCA comes from using the drug as a possible treatment for nonalcoholic steatohepatitis (NASH), which is anticipated to be the most lucrative market for OCA, according to the Thomson Reuters analysis. NASH is estimated to affect 2% to 3% of the global population and its incidence is expected to increase due to other factors that contribute to the disease, such as metabolic disease, obesity, and insulin resistance. There is currently no approved treatment for NASH. In 2015, Intercept received breakthrough therapy designation from the FDA for treating patients with nonalcoholic NASH with liver fibrosis. Intercept expects to complete a Phase III study for the NASH indication in 2021 to support a regulatory filing.

The Thomson Reuters analysis points out that there are further potential long-term competition for OCA in both the PCB and NASH markets. These include investigational drug candidates from GlaxoSmithKline (GSK) (GSK-2330672), Albireo (A-4250), CymaBay Therapeutics (MBX-8025), and Shire (SHP-625). The Thomson Reuters analysis points out that Genfit's PRAR alpha and delta agonist, elafibranor, is in Phase II studies and is expected to be OCA's main near-term competitor in the oral NASH market. Another possible competitor is Gilead Sciences' simtuzumab, an allosteric humanized monoclonal antibody, which is in Phase II studies as a treatment for reversing fibrosis associated with liver cirrhosis.

Other key contenders
Gilead Sciences' fixed dose combinations: emtricitabine + tenofovir alafenamide and tenofovir alafenamde + emtricitabine + rilpivirine. Gilead Sciences has two potential blockbusters: fixed-dose combinations to treat HIV infection. The company's tenofovir alefenamide fumarate (TAF), a nucleoside reverse transcriptase inhibitor, is a follow-on to Gilead's tenofovir disoproxil fumarate (TDF) and is being developed as a component of several fixed-dose combinations, notes the Thomson Reuters analysis, which points to two possible blockbusters. The first is the fixed-dose combination of emtricitabine + tenofovir alafenamide (F/TAF) with projected 2020 sales of $2.006 billion and tenofovir alafenamde + emtricitabine + rilpivirine (R/F/TAF) with projected 2020 sales of $1.572 billion, according to the Thomson Reuters analysis.

The F/TAF regime was filed for US and European Union (EU) approval in April and May 2015, respectively for treating HIV-1 infections in adults and pediatric patients age 12 or older, in combination with other HIV antiretroviral agents. A PDUFA date is set for April 7, 2016 in the US. Regulatory filings for the R/F/TAF regimen were submitted in July and August 2015, respectively in the US and EU. A priority review voucher, which Gilead acquired from Knight Therapeutics, was submitted with the US filling to expedite review.

In March 2016, the FDA approved Gilead Sciences’ Odefsey (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg or R/F/TAF) for the treatment of HIV-1 infection in certain patients. Emtricitabine and tenofovir alafenamide are from Gilead Sciences and rilpivirine is from Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen). Odefsey is Gilead's second TAF-based regimen to receive FDA approval. Odefsey is indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years of age and older who have no antiretroviral treatment history and HIV-1 RNA levels less than or equal to 100,000 copies per mL. Odefsey is also indicated as replacement for a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) for at least six months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Odefsey. The Odefsey approval is part of an ongoing development and commercialization agreement between Gilead and Janssen, first established in 2009. Under this agreement, Gilead is responsible for the manufacturing, registration, distribution, and commercialization of the product in most countries while Janssen will distribute it in approximately 17 markets and have co-detailing rights in several key markets, including the United States. The original agreement was established for the development and commercialization of Complera, marketed as Eviplera in the European Union, and expanded in 2014 to include Odefsey.

The Thomson Reuters analysis points out that Gilead has a strong position in the antiviral market overall and in the HIV market specifically. Key drugs from Gilead include Atripla (emtricitabine/efavirenz/TDF), Truvada (emtricitabine and tenofovir disoproxil fumarate), Stribild (cobicistat, elvitegravir, emtricitabine and tenofovir disoproxil fumarate), and Complera (emtricitabine, rilpivirine, and tenofovir disoproxil fumarate), which had 2014 combined sales of $9.2 billion. Patent expiry, however, for TDF begins in July 2017, points out the Thomson Reuters report, and Teva has entered into an agreement in principle to launch its generic version of the drug in December 2017. The generic entry of TDF is expected to impact Gilead negatively with its four-based TDF drugs expected to decline in sales to approximately $8.6 billion by 2020. The Thomson Reuters report points out that Gilead's TAF has the potential to protect Gilead from generic drug incursion as the TAF patents extend to 2025 in the US and to 2027 in the EU. Gilead's Genvoya (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (E/C/F/TAF) was the first TAF regime to enter the market in December 2015, and additional F/TAF-based regimes for HIV are currently under development.

On a competitive level, Gilead's TAF regimes will compete against other TAF regimes as well as from ViivHealthcare's Triumeq (abacavir, dolutegravir, and lamivudine). Viiv is a global specialist HIV company majority-owned by GSK with Pfizer and Shionogi as shareholders. Triumeq, which was launched in September 2014, has projected sales of $4.0 billion in 2020, according to Thomson Reuters estimates.

Merck & Co.'s Zepatier (elbasvir and grazoprevir). Merck & Co. is contending with a potential blockbuster with Zepatier (elbasvir and grazoprevir) for treating adult patients with chronic hepatitis C virus (HCV) genotype (GT) 1 or GT4 infection, with or without ribavirin. The drug, which was approved in the US in January 2016, is a once-daily, fixed-dose combination tablet containing the NS5A inhibitor elbasvir and the NS3/4A protease inhibitor grazoprevir. The FDA previously granted two breakthrough therapy designations to Zepatier, for the treatment of chronic HCV GT1 infection in patients with end-stage renal disease on hemodialysis and for the treatment of patients with chronic HCV GT4 infection. EU review is ongoing with a decision expected in mid-2016.

Zepatier is one of several interferon-free therapies competing in the HCV market. Other key drugs include Gilead's Harvoni (sofosbuvir and ledipasvir) and AbbVie's Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets co-packaged with dasabuvir tablets). Current forecasts project sales of $9.335 bilion for Harvoni and $1.749 billion for Viekira Pak in 2020, according to Thomson Reuters. Sales of Zepatier are projected at $636 million in 2016 and rising to $1.5 billion by 2020.

Abbvie and Genentech's venetoclax. Venetoclax, which is being developed by AbbVie in collaboration with Genentech, is a potential blockbuster for treating chronic lymphocytic leukemia (CLL) in adults who have received at least one prior therapy, including patients with 17p deletion, which is associated with a highly aggressive disease and resistance to chemotherapy. In January 2016, the FDA accepted AbbVie’s NDA granting priority review for venetoclax for CLL in adults who have received at least one prior therapy, including patients with 17p deletion. The FDA previously granted venetoclax breakthrough therapy designation in April 2015 for the treatment of CLL in previously treated patients with the 17p deletion genetic mutation. The European Medicines Agency also has validated its MAA for venetoclax for the treatment of patients with CLL with 17p deletion or TP53 mutation.

Venetoclax is an inhibitor of the B-cell lymphoma-2 (BCL-2) protein being developed in partnership with Genentech and Roche to treat CLL. Venetoclax is believed to lead some cells, including some cells with CLL, to undergo apoptosis, or cell death.

Venetoclax will compete with Imbruvica (ibrutinib), a Bruton’s tyrosine kinase inhibitor approved for use in four indications to treat three different types of blood cancers, including CLL, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. Imbruvica was developed by Johnson & Johnson's Janssen Pharmaceuticals and Pharmacyclics, which AbbVie acquired in 2015 for $21 billion. Venetoclax will also compete against Gilead Sciences' Zydelig (idelalisib) in CLL. Thomson Reuters estimates are $6.467 billion for Imbruvica in 2020, far exceeding sales of Zydelig at $722 million in 2020. Sales of venetoclax are projected at $168 million in 2016 and rising to $1.477 billion in 2020.

Acadia Pharmaceuticals' Nuplazid (pimavanserin). Another potential blockbuster comes from Acadia Pharmaceuticals, a San Diego, California-based biopharmaceutical company, with Nuplazid (pimavanserin), a drug to treat Parkinson disease psychosis (PDP). The drug represents a new class of treatments for PDP as a highly selective selective serotonin inverse agonist that targets 5-HT2A receptors without a worsening of motor symptoms. A PDUFA action date of May 1, 2016 is expected. Forecast sales are $74 million in 2016 and rising to $1.409 billion in 2020.

Nippon Shinyaku's and Acetelion's Uptravi (selexipag) Nippon Shinyaku and Acetelion received FDA approval in December 2015 for Uptravi (selexipag), a drug to treat pulmonary arterial hypertension (PAH) to delay disease progression and reduce the risk of hospitalization. The drug was launched in the US in January 2016.

Uptravi will complete for other drugs to treat PAH, most notably, Bayer Healthcare's soluble guanylate cyclase stimulator, Adempas (riociguat), and United Therapeutics' Orenitram (treprostinil). Projected sales of Adempas are $939 million in 2020 and $449 million for Orenitram, according to Thomson Reuters estimates. Sales of Uptravi are expected to reach $1.268 billion in 2020. Uptravi is expected to protect against the sales erosion of Acetelion's Tracleer (bosentan), also to treat PAH, due to the loss of patent protection and generic entry in 2015. Revenue from Tracleer is expected to decline from a peak high of $1.7 billion in 2011 to only $246 million in 2020.

For additional information on the year's most promising treatments may be found in the Thomson Reuters’ Drugs to Watch 2016 report.

Upcoming analysis: What drugs launched in 2015 have made the mark and are continuing a path to blockbuster status? In the second of a two-part series, Thomson Reuters shares insight on the leading market entries in 2015 in the March 9, 2016 edition of DCAT Value Chain Insights (VCI). 

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