Amgen’s R&D Group Focuses On Efficiency As Drug Cost Concerns Continue
Executive Summary
Scrip spoke with R&D head David Reese about improving R&D timelines and success rates, including through the use of genomics and proteomics, as data readouts near for key drugs in big indications.
Amgen Inc. has been working for years to improve the efficiency of its research and development group, but executive vice president of R&D David Reese said that when he moved into his role 18 months ago he looked at additional ways to streamline the organization so that it works within an industry business model that’s changing based on increasing concerns about the costs of new drugs.
“What I really did was take a basic approach and say, 'OK, what are our assumptions about the world over the next 10-15 years?’” Reese said in an interview during the recent J.P. Morgan Healthcare Conference in San Francisco. “The business model is changing, led by the US drug pricing discussion, and clearly the industry is in a state of evolution, so any R&D organization has to be prepared to produce what we want to do, which is transformative medicines for that world to come.”
Amgen has decided to focus its efforts on three therapeutic areas – cardiovascular disease, oncology and inflammation – and will have important clinical trial readouts across all three categories this year. Those three therapeutic areas represent a very large public health burden with annual mortality across the globe equal to the population of the state of California, Reese noted, which is 39.6 million.
“At the highest level, the mission statement of R&D [at Amgen] is transformative medicines for diseases with significant public health burden where we can actually help both patients and societies around the world as we confront an aging planet,” he said.
The executive outlined three strategic imperatives for achieving that goal:
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An “existential challenge” for the industry is the R&D success rate, since only about 8% of drug candidates make it to patients, Reese said. “We have to do better than that,” he added. “Our genetics and other -omics platforms are intended to really help us improve our odds there.”
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The second existential challenge is the time it takes to develop drugs from an idea in a research laboratory to a launch in the commercial market, which is about 12-14 years, on average. “We all understand that if that continues, we simply won’t be viable as an industry,” Reese said. “We have instituted a host of programs internally to improve cycle times. We've reduced, we think, probably three years on average right now. I think we can do better and we will do better going forward.”
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Lastly, Amgen’s R&D organization is becoming more focused on “enabling considerations for use and access across the drug development spectrum. It used to be that an R&D organization had a terminus of regulatory approval; that was the goal line. I would posit that now that’s perhaps less than half the battle. In fact, we need to ensure that the drugs we’re developing, and the evidence packages we're putting together, will enable those drugs to get to the patients that need them,” he said.
Working ‘Hand-In-Glove’ With Commercial Teams
Reese said that doesn’t mean Amgen’s commercial organization is determining what kind of fundamental discovery research is being done by the R&D group. However, he noted that the R&D organization could build a “hand-in-glove relationship” with their commercial colleagues shortly after a new drug candidate is identified to make sure clinical studies reflect the demands of patients, prescribers and payers in the indications where the medicine is being developed.
That may mean that members of Amgen’s commercial teams and its value and access organization sit in on some of the R&D group’s discovery research governance meetings.
“Now, they're not going to tell a chemist where to put a florine atom on a molecule, but they are going to say, 'Hey, here's the kind of world this molecule is likely to land in, here's what we need to think about, what we need for this being a drug that can really move the needle for patients and for payers around the world,’” Reese said. “I think creating that kind of dialog and bringing in medical affairs earlier in the research and discovery process are very practical things that can occur.”
Genetic Starting Points To Improve The End Game
Having genetics as a starting point is part of Amgen’s strategy for cutting the company’s R&D timelines and improving the success rate for its drug candidates, which ultimately should reduce the cost of producing new medicines.
For instance, developing drug candidates against proven genetic biomarkers helps the company cut the time and cost of early development, because fewer preclinical experiments are needed to validate the target. Genomic insights also can make sure appropriate patients are enrolled in clinical trials to increase the likelihood that the drug will perform as anticipated in those studies.
Amgen has invested heavily in genomics research, including through the acquisition of deCode genetics EHF in 2012, and it is investing in proteomics research under a partnership with SomaLogic Inc. Via deCODE, Amgen and SomaLogic are measuring and analyzing 5,000 proteins across all kinds of diseases in 40,000 people. (Also see "'Beautiful baton pass' as Amgen picks up deCODE to validate drug targets " - Scrip, 11 Dec, 2012.)
“That's 200 million data points and then you're uniting that with genetic data,” Reese said. “That will then also allow you not only to do additional target discovery and pathway discovery, but this sort of patient segmentation or stratification.”
Amgen also is beginning to look at transcriptomics – the study of the transcriptome, or the set of RNA molecules within a given cell. But while the company is narrowing its interests to unmet medical needs in large population diseases based on genomic, proteomic and transcriptomic insights, it no longer is focused on drug discovery for neurological diseases – a category that includes major unmet needs in big indications, such as Alzheimer’s disease.
“When I looked at our portfolio and where we think we can bring the most amount of leverage to bear and really move the needle in terms of developing transformative medicines, neuroscience to me was a challenge from a couple of perspectives,” Reese said.
First, the basic understanding of the biology of these diseases lags other therapeutic areas, he noted. Then this lack of biologic understanding is coupled with a lack of genetic or surrogate biomarkers. These deficits lead to lengthy clinical trial programs with no early predictors of the studies’ potential outcomes.
“That said, we remain interested and I think genetics is actually going to drive that field – it has to,” Reese said, noting that Amgen still is exploring neuroinflammation in its inflammation R&D group and that it may look for ways to outsource neuroscience assets that have been deprioritized.
Bringing Drugs To Market Faster
At the same time that it has invested in genetic research, Amgen also has closely examined its drug development processes from the research laboratory to the commercial market to see where it can shorten the timeline for bringing new medicines. Reese led that project under prior EVP of R&D Sean Harper, who left the company in 2018 to work in venture capital. (Also see "Finance Watch: Three New Funds, Including Former Amgen R&D Head Harper's Next Venture" - Scrip, 7 Sep, 2018.)
Reese said the R&D organization looked at “where can you actually shrink timelines – eliminate white spaces in transitions of molecules as they go from preclinical to Phase I, Phase II and Phase III? What are things you can do in parallel to cut down time that you normally would have done sequentially, if you choose to?”
Reese said the company is applying the lessons learned through that process, with its KRAS inhibitor AMG 510 being a notable beneficiary of that exercise. AMG 510 moved from preclinical to clinical development in a matter of months “and now 17 or 18 months since the first patient was dosed, we're moving along in Phase II, we'll have Phase II data [in lung cancer] over the course of this year,” he said. As a result, the closely watched drug is the most advanced program in the KRAS class.
However, rapidly advancing a cancer drug in a subset of patients with a specific tumor type is different from quickly developing a drug for a large group of patients with cardiovascular disease. But Amgen is optimistic that it can move forward faster in that therapeutic area, which it is trying to do with the Phase I candidate AMG 890 – a small interfering RNA (siRNA) drug that targets lipoprotein(a), or Lp(a).
“I think the way forward there comes back to genetics and allied technologies,” Reese said. “In the Lp(a) program [we’re] using genetics and other technologies to say here are the patients we really think are the highest risk that are going to benefit the most, so you can design a very efficient development program.”
While cardiovascular outcomes studies may still be required to confirm safety in a big patient population, he said identifying trial participants based on genetic markers may mean that outcomes studies do not have to be as large at the FOURIER outcomes trial that enrolled over 27,000 patients to confirm the cardiovascular benefits of Amgen’s PCSK9 inhibitor Repatha (evolocumab). (Also see "Is Amgen's FOURIER Enough For Physicians, Payers To Expand Repatha Use?" - Scrip, 17 Mar, 2017.)
Heart Failure, Cancer Studies Among 2020 Readouts
A Phase III readout for another cardiovascular disease drug is among several major milestones for Amgen’s R&D pipeline in 2020. The company may finally have Phase III results later this year from a long-running study of omecamtiv mecarbil in the treatment of heart failure. (Also see "Heart Failure Pipeline Review: Amgen's Omecamtiv And Merck's Vericiguat Step Up To Plate" - Scrip, 16 Feb, 2018.)
The novel small molecule developed in partnership with Cytokinetics Inc. directly targets and selectively activates cardiac myosin, a heart muscle protein involved in cardiac contraction; Servier SA has rights to the candidate in certain markets. (Also see "Amgen, Servier strike deal to sell, develop heart drugs" - Scrip, 9 Jul, 2013.)
Amgen also expects Phase III results this year for tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP) and developed in partnership with AstraZeneca PLC, in severe asthma. (Also see "AstraZeneca Respiratory Head: Tezepelumab Could Be 'Game Changer'" - Scrip, 8 Sep, 2017.)
Phase III results are anticipated in 2020 as well for Otezla (apremilast) in mild-to-moderate psoriasis. Amgen acquired the phosphodiesterase 4 (PDE4) inhibitor late last year, a divestiture required in Bristol-Myers Squibb Co.’s $74bn acquisition of Celgene Corp. The oral drug is approved for moderate-to-severe psoriasis where Celgene positioned it as a treatment option after topical therapies, but before biologics. (Also see "Amgen's $13.4bn Otezla Buy Helps Bristol/Celgene Merger Close By Year-End" - Scrip, 26 Aug, 2019.)
Early- and mid-stage clinical trial readouts for Amgen in 2020 include early data from the ongoing Phase II trial for AMG 510 in non-small cell lung cancer (NSCLC) patients with a KRAS G12C mutation as well as Phase I data for AMG 510 monotherapy in solid tumors, and for the combination of AMG 510 with Merck & Co. Inc.’s PD-1 inhibitor Keytruda (pembrolizumab) in NSCLC.
First-in-human data also are expected this year for AMG 701, a half-life-extended bispecific T-cell engager (BiTE) targeting B-cell maturation antigen (BCMA) for the treatment of multiple myeloma. (Also see "Interview: Amgen's BiTE Platform Becomes A Feast As More Molecules Enter The Clinic" - Scrip, 6 Mar, 2018.) The company’s first-generation anti-BCMA BiTE, AMG 420 already has generated Phase I results in multiple myeloma. (Also see "ASH Preview: BCMA-Targeting CAR-Ts And Bispecifics Hog The Spotlight" - Scrip, 28 Nov, 2018.)
Beyond tezepelumab for severe asthma, Amgen has multiple other drug candidates in the clinic within its inflammation R&D pipeline, including AMG 570, a bispecific antibody targeting ICOS and BAFF that’s in Phase II for the treatment of systemic lupus erythematosus (SLE). AMG 592, an interleukin-2 (IL-2) mutein – a mutated version of IL-2 designed to enhance the number and function of T-regulatory cells – is in Phase I and may be developed to treat SLE, rheumatoid arthritis and graft-versus-host disease.
Amgen also continues to augment its own R&D with assets from outside of its laboratories and in ex-US markets, as it did through its recently closed partnership with BeiGene Ltd. in China. Reese said the company has financial capacity for additional deals even after the multibillion-dollar Otezla and BeiGene transactions. (Also see "Amgen Joins China Oncology Market Race With $2.7bn BeiGene Stake" - Scrip, 1 Nov, 2019.)
“Our approach to business development and M&A will not really change,” Reese said. “Going forward, our greatest interest, of course, are things within our core therapeutic areas and we look for deals where we feel that both parties will benefit – technology platforms through late-stage assets, like Otezla. All of that remains in our scope.”