Decision Resources Group’s analysts looked back at the key cardiovascular, metabolic, renal, and hematological market events that shaped 2018. Below are the news stories that generated the most discussion among the team last year:

 

Praluent’s ODYSSEY outcomes trial

At the American College of Cardiology's Annual Scientific Session in March, Sanofi and Regeneron presented data from the ODYSSEY outcomes trial, demonstrating that the PCSK9i Praluent (alirocumab), significantly reduced the risk of major adverse cardiovascular events (MACE) in patients who had suffered a recent acute coronary syndrome (ACS) event. Praluent demonstrated a 15% reduction in all-cause mortality, a claim its PCSK9i competitor cannot make; Amgen’s Repatha did not show a mortality reduction in the FOURIER outcomes trial. Moving into 2019, key competitive factors between the two PCSK9is are going to be price and market access; both companies have announced radical discounting or reductions to list prices.

 

Factor Xa inhibitor reversal agent

May 2018 saw the much-awaited approval of the first reversal agent for factor Xa inhibitors in the United States. Portola’s Andexxa was approved for use in patients receiving Xarelto (rivaroxaban) and Eliquis (apixaban) in case of life-threatening or uncontrolled bleeding. The availability of an antidote is expected to fulfill a long-established unmet need and conciliate physicians’ concern around the use of NOACs in high risk patients.

 

Belviq and CV safety

Given the medical community’s unease over potential CV harm from centrally acting obesity therapies, many companies have been forced to undertake post-marketing CVOT trials for their drugs. In June, Eisai announced that whilst there was no CV benefit from treatment with Belviq, it did not cause any increased CV harm (although questions do remain on it increasing the incidence of suicidal ideation).

 

Invokana’s renal outcomes trial

Following on from the encouraging results in the CANVAS-R trial, it was reported in July that the Phase 3 CREDENCE renal outcomes trial of Janssen’s Invokana (canagliflozin) was halted early owing to positive results. Benefit was shown for the composite end point of time to dialysis or kidney transplantation, doubling of serum creatinine, and renal or cardiovascular death, when used in addition to standard of care. Invokana and other members of the SGLT-2 inhibitor class have the potential to be the first new therapies in more than a decade to slow progression of diabetic kidney disease.

 

Xarelto in PAD/CAD

The approval of Xarelto for PAD/CAD in Europe (August) and the United States (October) has sparked a renewed enthusiasm for the management of the disease. The approvals were based on robust results from the COMPASS trial. With no direct competition in the anticoagulant space in this setting, Xarelto is expected to capture a significant share of the PAD market. Results from the ongoing Phase III VOYAGER-PAD study are expected to add to the growing evidence-base for use of Xarelto in the PAD population.

 

Hemlibra for noninhibitor hemophilia A

In October, the FDA extended Roche’s Hemlibra label to include noninhibitor hemophilia A patients. Hemlibra's dramatically reduced dosing frequency and subcutaneous administration, compared with three-times-weekly intravenous factor VIII, provides an important alternative prophylaxis treatment option. Expansion beyond inhibitor patients opens up Hemlibra to a much larger patient population, which will drive brand sales.

 

GIP/GLP-1 dual agonist in T2D

In October, Eli Lilly published impressive results from its Phase II trial studying tirzepatide (LY3298176) in T2D. This once-weekly GIP/GLP-1 dual agonist, dubbed a twincretin, showed impressive reductions in blood glucose and weight loss, proving significantly better than Eli Lilly’s GLP-1 receptor agonist, Trulicity (dulaglutide). Off the back of these results, Eli Lilly is now proceeding full steam ahead with its Phase III SURPASS program, which will look at the drug’s safety and efficacy for treating type 2 diabetes. If successful, tirzepatide could be the vanguard in a shift towards more dual or even triple co-agonists.

 

Vascepa’s REDUCE-IT outcomes data

Amarin’s Vascepa blew away expectations of its outcomes trial, REDUCE-IT, reported at the American Heart Association’s (AHA) Scientific Sessions in November. In the context of previous failed attempts to demonstrate that omega-3 fatty acids reduce cardiovascular risk, the 25% relative risk reduction of Vascepa over placebo was particularly ground-breaking. Some questions remain over exactly how it is working this well, and if the choice of placebo exaggerated the magnitude of effect. Targeting TGs is back into the spotlight in dyslipidemia, and a source of sales growth following the decline of statin revenues.

 

THR-ß agonists in NASH

Many patients with NASH also have comorbid T2D, dyslipidemia, and obesity. Phase II results were presented in November for two novel THR-ß agonists, Madrigal’s MGL-3196 and Viking’s VK-2809. These agents showed that in addition to lowering hepatic fat and markers of fibrosis, they had positive impacts on various lipid parameters, possibly kick-starting a more holistic approach to treating NASH and the metabolic syndrome.

 

Guidance documents for NASH drug development

With no therapies approved for the treatment of NASH and with only 4 drugs in active Phase III development, the late-stage development and regulatory landscape remains unchartered territory. In November, both the U.S FDA and the EMA released draft guidance documents for the development of NASH drug treatments. As we saw with the obesity space over a decade ago, guidance for industry documentation helps manufacturers with trial design and influences discussion at Advisory Committee meetings, prior to regulatory approval decisions.

 

Farxiga/Forxiga’s CV outcomes data

The DECLARE-TIMI 58 trial evaluated the effects of the SGLT-2 inhibitor, dapagliflozin (AstraZeneca’s Farxiga/Forxiga), on CV outcomes in patients with T2D with or at risk of atherosclerotic cardiovascular disease (ASCVD). Results, presented at the AHA Scientific Sessions in November, showed that while it failed to demonstrate a reduction in MACE, similar to the CVOT results for two other SGLT-2 inhibitors, it did show a statistically-significant reduction versus placebo in the composite end point of hospitalization for heart failure or CV death.

 

In-hospital initiation of Entresto

Results from the PIONEER-HF trial were presented at the AHA Scientific Sessions in November and demonstrated that starting Entresto during hospitalization for acute decompensation in heart failure with reduced ejection fraction (HFrEF) reduced NT-proBNP concentrations and heart failure rehospitalizations. This result opens the door for Entresto use in the inpatient and hospital discharge settings, where interviewed KOLs tell us most of the key prescribing decisions occur.

 

Positive data for oral semaglutide

In November, Novo Nordisk released positive top-line results from its Phase III PIONEER 6 trial studying the oral once-daily GLP-1 analogue semaglutide in T2D. As expected, oral semaglutide demonstrated non-inferiority for MACE. Although it did not show superiority in reducing MACE, there were significant reductions in CV deaths, and all-cause mortality of 51% and 49%, respectively. We expect these encouraging data to give the first oral GLP-1 analogue a huge boost when launched, and also add positive sentiment for Ozempic, the once-weekly injectable formulation of semaglutide.

 

Relevant Reports:

Venous Thromboembolism | Landscape & Forecast | Disease Landscape & Forecast
Peripheral Arterial Disease | Landscape and Forecast | Disease Landscape and Forecast
Non-alcoholic Steatohepatitis | Landscape & Forecast | Disease Landscape & Forecast
Hemophilia | Landscape & Forecast | Disease Landscape & Forecast
Type 1 Diabetes | Landscape & Forecast | Disease Landscape & Forecast
Type 2 Diabetes | Landscape & Forecast | Disease Landscape & Forecast
Obesity/Overweight | Landscape & Forecast | Disease Landscape & Forecast
Pulmonary Hypertension | Landscape & Forecast | Disease Landscape & Forecast
Dyslipidemia | Landscape & Forecast | Disease Landscape & Forecast
Heart Failure | Landscape & Forecast | Disease Landscape & Forecast
Diabetic Nephropathy | Landscape & Forecast | Disease Landscape & Forecast

 

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