Calling all heart docs – your diabetes drugs need you

Astrazeneca followed Johnson & Johnson and Eli Lilly this morning by delivering a disappointing performance from its SGLT-2 inhibitor Farxiga. The drug belongs to a class that is widely projected to become the fastest growing among diabetes medicines (see tables below).

As such, weak first-quarter sales from the main players is worrying, and the blame is being laid at the feet of US pricing pressures. Diabetes is an area where payers have successfully flexed their muscles. However, it seems that another factor is playing a role: the message that this class can reduce a patient’s risks from heart disease is taking time to have an impact.

Outpacing the market
Annual WW sales ($bn)
2016 2022e CAGR
SGLT2 inhibitors 2.9 9.6 22%
GLP-1 agonists 5.0 12.7 17%
Fast-acting insulin 7.5 7.3 (1%)
Long-acting insulin 10.3 9.7 (1%)
DPP-IV inhibitors 8.1 7.3 (2%)
Total diabetes market  43.6 58.2 5%
Source: EvaluatePharma. Class numbers exclude certain combination products

Astrazeneca said growing intra-class competition and the impact of affordability programmes and managed-care access subdued Farxiga growth in the US, where sales inched only 2% higher, to $96m, in the first quarter.

J&J painted an even worse picture with Invokana – lower prices caused US sales of the medicine to fall 13% on the same quarter of last year. The company also blamed increasing discounts for managed care and a higher composition of Medicaid sales, where prices are typically lower.

The Lilly result was probably the most surprising given that the company has been heavily marketing Jardiance’s success in its cardiovascular outcome study since January. New patient starts have surged 75% since the company was allowed to begin marketing on evidence that the drug can reduce the risks of death and complications from heart disease, the company said this week. However revenues still came in lower than the sell-side was expecting.

A disappointing Q1 for the SGLT-2s 
Annual WW sales ($m)
Product Company Q1'17a Consensus 2017e 2022e
Jardiance Boehringer Ingelheim n/a n/a 929 3,514
Jardiance Eli Lilly* 74 85 468 1,781
Invokana Johnson & Johnson 284 337 1,981 3,138
Farxiga AstraZeneca 207 245 1,101 1,937
*Alliance revenue
Source: Analyst reports, EvaluatePharma

Lilly and partner Boehringer Ingelheim are the only companies allowed to actively market a cardiac benefit for their SGLT2, although big studies are due to report on Invokana and Farxiga in the next couple of years. These are widely expected to confirm a class effect, helping to drive use of all of these medicines (ACC – Jardiance heart benefit looks like a class effect, March 20, 2017).

However, the finding represents a big philosophical shift for this area of medicine, which is more used to dealing with the discovery of safety signals.

“We have to remember we are talking about changing very well entrenched treatment practises and physicians do take some time to get comfortable with new drugs and new classes,” said Mark Mallon, head of Astrazeneca’s global product strategy and medical affairs, in a media call this morning. “They need to see the data and the data is absolutely coming. But it’s going to take time to build that up.”

Assuming the class effect is confirmed, having three companies actively promoting a cardiac benefit will surely help drive uptake. However another issue is bringing cardiologists on board – endocrinologists and primary care doctors are currently the main prescribers of these drugs – an issue that Lilly executives have said they are closely monitoring.

“Cardiologists, in the case of Jardiance, are a significant source of authority. And while we have seen an increase, the base of prescribing is extremely, extremely small,” Enrique Conterno, head of Lilly’s diabetes business, told analysts on a call last week.

Merging therapy areas

The discovery of cardioprotective benefits for the SGLT2s and to a lesser extent the GLP-1 agonists points to a merging of therapy areas that looks set to become only more apparent in the coming years.

Novo Nordisk has already won approval for Victoza as an obesity therapy. Astrazeneca this year started two outcome trials with Farxiga in heart failure and chronic kidney disease, which will recruit both diabetic and non-diabetic patients. And its blood thinner Brilinta is being trialled in diabetic patients in the huge Themis study, to see if it can reduce the risk of heart attack and stroke.

The UK pharma giant has even merged its cardiovascular and diabetes drugs into a single reporting unit, which chief executive Pascal Soriot put down to more and more overlap.

“We believe there are substantial synergies across those therapy areas – operationally in the field but also from a medical view point,” he told journalists earlier today.

A cynic might also see the move as a convenient way to de-emphasise Brilinta, sales of which have long disappointed.

However it is readily apparent that the SGLT2s have the potential to steer the treatment of diabetics closer to the cardiovascular world than ever before. The extent to which these drugs will be embraced by cardiologists is hard to foresee until more trials report, but could have a huge impact on the commercial potential of the class.

Outcome trials underway
Trial ID  Enrollment  Data due
Farxiga Dapa-CKD NCT03036150 4,000 2020
Dapa-HF NCT03036124 4,500 2020
DECLARE-TIMI58 NCT01730534 25,880 2019
Brilinta THEMIS NCT01991795 20,185 2018
Invokana  Canvas  NCT01032629 4,330 ADA in June

To contact the writer of this story email Amy Brown in London at [email protected] or follow @ByAmyBrown on Twitter.

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