AstraZeneca's Dobber On Ramping In Renal, Expanding In CV And Business Development
Executive Summary
Biopharmaceuticals President Ruud Dobber talked to Scrip about the launches of Lokelma and roxadustat in kidney disease, building with a high bar in cardiovascular disease and expanding in cell and gene therapy.
This year AstraZeneca PLC Biopharmaceuticals President Ruud Dobber is focused on executing on the company's expansion into kidney disease with the launch of Lokelma (sodium zirconium cyclosilicate) underway for hyperkalemia and a second potential approval, roxadustat, anticipated later in 2020.
Dobber, who oversees AstraZeneca's global drug portfolio outside of oncology, talked with Scrip at the J.P. Morgan Healthcare conference in San Francisco on 14 January. He has been leading the biopharmaceuticals business for a year, having previously run AstraZeneca's North American commercial operations. He discussed the ongoing expansion in renal disease, the company's commitment to cardiovascular disease, including the move into heart failure, and business development.
The commercial oncology business is overseen by David Fredrickson, who separately talked to Scrip about the launch of Enhertu (trastuzumab deruxtecan) in HER2-positive breast cancer. (Also see "J.P. Morgan Notebook Day 2: Bourla Feels Pfizer's Underappreciated, GSK Prepares For Myeloma First And More" - Scrip, 15 Jan, 2020.)
Among the launches on the biopharmaceutical side of the business are two in renal disease: Lokelma, which was approved by the US Food and Drug Administration (FDA) for hyperkalemia in 2018 but didn't launch until mid-2019, and roxadustat for the treatment of patients with anemia from chronic kidney disease.
Dobber confirmed that AstraZeneca filed an application for roxadustat with the FDA before the end of the year. The drug, developed with partner FibroGen Inc., is a first-in-class HIF-PH inhibitor that has shown improved safety and efficacy in clinical trials over the standard of care, erythropoiesis-stimulating agents, and which AstraZeneca hopes will be approved for both CKD patients on dialysis and those not on dialysis. (Also see "Clear Path For AstraZeneca’s Roxadustat After Reassuring Safety Data" - Scrip, 11 Nov, 2019.) (Editor's note: this story has been updated to reflect that AstraZeneca expects FDA approval , but not necessarily the launch, of roxadustat in 2020).
Building Market Access In "A Tough Area"
Both launches are core elements of AstraZeneca's strategy to expand in kidney disease beyond diabetes, where it has long had a presence. In 2018, AstraZeneca renamed its CVMD (cardiovascular/metabolic disease) therapy area to CVRM (cardiovascular/renal medicine) to reflect the growing emphasis on renal disease outside of diabetes. (Also see "Next Up For AstraZeneca: Building Out In Renal Disease " - Scrip, 24 Oct, 2018.)
Both launches will be challenging as AstraZeneca ramps up in a new space that presents specific market access challenges, both around commercial payer dynamics and Medicare restrictions for drugs administered in dialysis centers under the end-stage renal disease bundled payment system.
"From a market access perspective this is a tough area," Dobber acknowledged.
The company has established a renal commercial sales force for the launch of Lokelma, which will likely be expanded to support the launch of roxadustat, Dobber said.
With the launch of Lokelma, AstraZeneca is competing against Vifor Pharma Group's Veltassa (patiromer), which was approved by the FDA in 2015, but carries warnings about constipation and can interact with other oral drugs. (Also see "Relypsa’s Potassium-Lowering Drug Clears FDA, But Dosing Warning Could Impact Use" - Pink Sheet, 22 Oct, 2015.)
"We are extremely pleased because within the six months after the commercial launch we are equivalent or even higher in what is called new-to-brand prescriptions, which is an incredible achievement of the medical and commercial team so quickly," Dobber said.
There is significant underdiagnosis in the space because of lack of awareness on the part of general practitioners and cardiologists and to a smaller extent nephrologists, the exec explained.
Hyperkalemia is high serum potassium concentration in the blood that can be asymptomatic but can cause long-term damage. It is often caused by CKD or other metabolic deficiencies. The standard of care has been a restrictive diet or an old generic medicine, sodium polystyrene sulfonate, that carries a lot of side effects. There are roughly 3 million patients in the US with hyperkalemia, according to AstraZeneca.
"Hyperkalemia is not always seen by payers as an area of high unmet medical need, so we need to do a lot of education," Dobber said. "Our access is getting better every day and the expectation clearly is that we will exceed Veltassa for 2020 from a prescription standpoint."
Senior VP for market access Rick Suarez also talked to Scrip about the launch. "We are very pleased with payers' willingness to add it to formulary and preferred positions at that," Suarez said. "Some of the largest Medicare payers in the country have done so, and we are also seeing very good uptake in hospitals."
As for the anticipated launch of roxadustat, Dobber said it is a complex product with two separate segments of the market to target, dialysis and non-dialysis.
"We will have specific people detailing in the dialysis centers versus [to] nephrologists working in hospitals and clinics," he said. "We have a very strong field force already but probably it is reasonable to say that we will expand it a little bit more."
As for the challenging reimbursement environment for bundled payments in dialysis centers under Medicare, Suarez said the company is prepared.
"The bundles create their own challenges because the legislative environment can change at any time, but we feel we have a good grasp of how it is currently reimbursed and how our product will be treated in the bundle," Suarez said. "Time will tell."
Moving Beyond Diabetes With Farxiga
In addition to the two new launches, AstraZeneca also has a potential large commercial opportunity coming in the first half of the year from the approval of the diabetes pill Farxiga (dapagliflozin) for the treatment of heart failure. The FDA granted a priority review for Farixga for the reduction of cardiovascular death or worsening of heart failure in adults with reduced ejection fraction (HFrEF) both with and without type 2 diabetes, with action expected in the second quarter. (Also see "AZ’s Farxiga Gets FDA Priority Review For Heart Failure" - Scrip, 6 Jan, 2020.)
The filing represents a significant opportunity for AstraZeneca to expand the SGLT2 inhibitor outside of diabetics. Farxiga was already approved to reduce the risk of hospitalizations for heart failure in type 2 diabetics with cardiovascular risk factors in October, the first SGLT2 to win the indication.
"It will open up a completely new patient population," Dobber said. "We have high expectations of course for this opportunity." The expanded filing was based on the Phase III DAPA-HF trial that showed the drug reduced the composite endpoint of cardiovascular death or worsening heart failure by 26% when given on top of standard of care, with benefits seen in both diabetics and non-diabetics. (Also see "Farxiga Data Change Heart Failure Treatment Outlook" - Scrip, 2 Sep, 2019.)
He said AstraZeneca will remain committed to the diabetes space, but that within diabetes, the focus will move more toward cardiovascular disease and comorbidities of diabetic patients. That comes after another major diabetes player, Sanofi, announced in December that it will end diabetes research altogether. (Also see "Sanofi, Long-Time Leader In Diabetes, Is Exiting Diabetes Research " - Scrip, 10 Dec, 2019.)
A High Bar For Cardiovascular Disease
At a time when there is some renewed interest in the cardiovascular disease therapy among some big pharma players, Dobber reiterated AstraZeneca's commitment to the space.
"There is a lot of attention of oncology and the breakthroughs in oncology, but we need to understand the number one killer in the world is still cardiovascular disease by far," he said. AstraZeneca is looking increasingly at inflammation as a trigger for atherosclerotic plaques and heart attacks, with work ongoing in R&D.
But it is a challenging space. He pointed to AstraZeneca's experience with Epanova (omega-3-carboxylic acids) as an example of just how tough the cardiovascular space can be. The company announced on 13 January the discontinuation of the cardiovascular outcomes trial testing Epanova in patients with high triglycerides who are at increased risk of cardiovascular disease due to a low likelihood of success. (Also see "AZ Halts Epanova Study As High Placebo Effect Kills Acasti’s Omega-3 TRILOGY-1 Trial " - Scrip, 14 Jan, 2020.)
The drug was first approved by the FDA in 2014 for the treatment of high triglycerides, but a positive cardiovascular outcomes trial would have opened the drug up to a potentially broader cardiovascular risk reduction claim. A rival drug, Amarin Corp. PLC's Vascepa (icosapent ethyl), has succeeded where Epanova failed, resulting in mega-blockbuster sales expectations from some analysts. (Also see "Sales Already Growing As Vascepa Secures Cardio Approval" - Scrip, 16 Dec, 2019.)
"This is a very hard place because the bar is very high," Dobber said of the cardiovascular therapeutic area. "But that makes it also very attractive if you find a molecule that can further reduce [the risks]."
As for building in cardiovascular disease through business development, Dobber said it is challenging to find a breakthrough asset. "As a large company, we are scanning every day potential opportunities," he stated. He said CEO Pascal Soriot and chief financial officer Marc Donoyer would take a critical view of any assets he might bring to their attention because of the high valuations. But, he added, “if it makes sense, there is a clear willingness to in-license or buy those new assets, but there are not too many," he said.
Two areas AstraZeneca has identified as new areas for expansion are gene therapy and cell therapy, he added. "It is fair to say we are not one of the frontrunners at the moment, but clearly there is a huge commitment from our R&D colleagues in order to have a close look," Dobber noted.