Obesity Market Gains Weight But Better Drugs Still Needed

The US obesity market is expected to double in size over the next decade with Novo Nordisk’s Saxenda driving the growth – but real progress for the pharmaceutical sector will only come when obesity drugs offer better outcomes than non-pharma methods.

The US obesity market is set to grow from $533m to $1.2bn in the next 10 years, according to Datamonitor Healthcare’s obesity forecast. However, there is room for more dramatic growth long term should more efficacious therapeutics come to market. Fewer than than 1% of treatable patients currently receive a pharmacological intervention for obesity. The market could be worth $11.2bn by 2026 if the proportion of obese patients receiving drug therapy increased to 5%, or $22.4bn if it was 10% (see Figure 1).

The predicted boost in the obesity drug market will be mainly contributed by Novo Nordisk AS' liraglutide(Victoza/Saxenda), for which cardiovascular data from Victoza’s LEADER trial has shown 13% reduced risk of major adverse CV events in patients with type 2 diabetes. With cardiovascular disease one of the leading co-morbidities linked to obesity, Saxenda has an advantage over its competitors. In Datamonitor Healthcare’s 2016 primary research survey, 42% of physicians said that they already intend to increase their use of Saxenda. With its CV risk reduction data and increased physician acceptance for effective pharmacological treatments, the drug’s sales are expected to grow from $261m in 2016 to $778m in 2026, with the greatest uptake in patients who are at a higher risk of CV events with grades 2 and 3 obesity (see Figure 2).

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Figure 1

Price rather than market share will be a key driver of Saxenda's domination of the market: its monthly treatment cost is estimated to be about $1,000, compared with $558 for the next most expensive treatment, Roche's Xenical (orlistat). Vivus's Qsymia (phentermine/topiramate) is expected to continue to be the most commonly prescribed weight loss product.

Increasing sales of Qsymia and Orexigen Therapeutics Inc.'s Contrave (bupropion/naltrexone) will also contribute to the obesity market growth over the next few years and will surpass the declining sales of Xenical and Eisai Inc.'s Belviq (lorcaserin). Xenical and Belviq are less effective than Qysmia, Saxenda and Contrave, resulting in a reduced patient share and declining revenues. Xenical’s revenue is expected to decrease from $116m in 2016 to $78m in 2026, while Belviq's will decline from $41m to $18m.

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Figure 2

Contrave's prospects are constrained by Takeda having pulled out of its partnership with Orexigen, leaving the smaller, resource-constrained partner with sole responsibility for marketing the drug. (Also see "Obesity Market Snapshot: Marketing Partners Giving Obesity The Slow Goodbye" - Scrip, 9 May, 2016.) However, sales will grow because physicians are likely to become more accepting of pharmaceutical interventions for obesity. In the DMHC forecast, it says that "physicians are slowly beginning to prescribe pharmacological therapy for weight loss more often as knowledge of the drugs increases and the economic cost of obesity grows."

Vivus’ Qysmia will likely benefit from Takeda's abandonment of Contrave, possibly gaining the additional patient share that Contrave will lose. Qysmia already has the largest single share of the obesity market and is expected to remain the most commonly prescribed weight loss drug - its strong efficacy data from clinical studies gives the drug an upper hand over competitor weight loss drugs.

As physicians become more accustomed to drug therapies for weight loss it is expected that more candidates will reach the market. Currently there are 16 late-stage drugs in Phase II development, with pipeline leader Medix planning to initiate Phase III studies for tesofensine before the end of 2016 [see table below].

Datamonitor Healthcare analyst Kevin Shannon, author of the report, highlighted Johnson & Johnson's Invokana (canagliflozin), currently the leading SGLT-2 inhibitor in type 2 diabetes, and Novo Nordisk's Victoza/Saxenda follow on, semaglutide (NN9536), as the most significant drugs in the pipeline.

Boehringer Ingelheim GMBH/Eli Lilly & Co.'s Jardiance (empaglifozin), another SGLT-2 inhibitor, recently showed a reduction in cardiovascular events in type 2 diabetes in a large scale CV outcomes trial; it is expected that Invokana should follow suit. "This is generally believed to be a class benefit, though we won’t know for certain until Invokana announces the results of its CVOT in 2017," Shannon noted.

Semaglutide has also demonstrated a CV benefit in type 2 diabetes (Also see "EASD 2016: Semaglutide Steals The Show With Impressive Cardiovascular Outcomes Data" - Scrip, 16 Sep, 2016.). Novo Nordisk is working on an oral formulation for the drug, something Shannon believes could be big.

There have also been some trials combining SGLT-2 inhibitors and GLP-1 agonists in type 2 diabetes with a particular interest in the weight loss effect. The results from these studies so far do show impressive weight loss, suggesting another option for future treatment in obesity. One such study was AstraZeneca PLC's DURATION-8 trial, which examined a combination of the SGLT-inhibitor dapagliflozin and the GLP-1 receptor agonist exenatide in patients with inadequately controlled type 2 diabetes; as well as meeting its primary endpoint of HbA1c reduction from baseline compared with either drug alone, it met secondary endpoints including significantly greater body weight reduction compared with either drug alone.

Saniona's tesofensine and 7TM Pharma AS' obinepitide are both central nervous system acting drugs, a feature that may actually limit their success in Shannon's opinion. He noted previous setbacks with this type of drug in the obesity space, including the withdrawal of rimonabant, sibutramine and fenfluramine/phemtermine.

Table: Late-stage Obesity Pipeline Drugs

Drug	Company	Phase	Target	Route of Administration
IONIS-FGFR4Rx	Ionis Pharmaceuticals Inc.	II	Fibroblast Growth Factor Receptor (FGFR)	Unspecified
setmelanotide	Rhythm Pharmaceuticals Inc.	II	Insulin Receptor/ Melanocortin (MC) receptors	Subcutaneous
OBEP-100	Medlab Clinical	II	Unspecified	Oral
EMP-16 (acarbose + orlistat)	Empros Pharma	II	Lipase inhibitor / Cholesterol inhibitor	Oral
LIK-066	Novartis AG	II	Oral sodium-dependent glucose cotransporter (SGLT)-1 and -2	Oral
Oral HDV Biotin	Diasome Pharmaceuticals Inc.	II	Unspecified	Oral
GPP-846	Gene PreDiT	II	Nucleotide polymorphisms (SNPs) of GP0044 gene	Oral
MB-11055	KT&G Life Sciences	II	AMP-activated protein kinase	Unspecified
langlenatide (SAR-439977; HM-11260C; LAPS-Exd4)	Hanmi Pharmaceutical Co. Ltd.	II	Glucagon-like peptide 1 (GLP-1) receptor	Injectable, subcutaneous
Invokana (canagliflozin)	Johnson & Johnson	II	sodium-dependent glucose cotransporter (SGLT)	Oral
obinepitide	7TM Pharma AS	II	Neuropeptide Y (NPY)/Peptide YY (PYY) Receptors	Subcutaneous
SAR439977 (efpeglenatide)	Sanofi	II	Glucagon-like peptide 1 (GLP-1) Receptor	Subcutaneous
tesofensine	Saniona AB in collaboration with Medix Inc.	II [plans to initiate Phase III]	Dopamine/norepinephrine (Noradrenaline) /serotonin receptors	Oral
Sarconeos BIO-101	Biophytis	II	MAS receptor	Oral
Oral HDV-I	Diasome Pharmaceuticals	II	Insulin Receptor	Oral
Semaglutide (NN9536)	Novo Nordisk AS	II	GLP-1 Receptor	Subcutaneous

Source: BioMedTracker and Citeline Pharmaprojects

In 2014, the cost of obesity in the US was estimated at $300bn – a price tag that is expected to skyrocket as the proportion of the US population classified as obese rises from 36% to a projected 50% by 2030. With only 1% of the potential patient population actually receiving pharmaceutical treatment, there is room for dramatic expansion of the market by size and value, particularly if more effective therapies are approved.

Challenges for the drug sector though will continue until companies can display strong efficacy results in trials targeting an obesity indication and not a sub-effect from other metabolic clinical studies.

Novo Nordisk is one diabetes company that has recently announced its desire to expand into other metabolic indications; and it is likely other big diabetes firms will follow this route. Increasing competition, a tough drug pricing arena and huge improvements in available treatments effectively curing certain type 2 diabetes patients will push more companies to seek other therapy areas for R&D. Obesity makes a logical sidestep for former diabetes focused companies and will continue to grow as a competitive landscape over the next decade.

Data from Datamonitor Healthcare. For more information on the research covered in this article, clickhere.