BIO 2019 Notebook: Merck On Finding The Right Balance, Sandoz On The Next Wave Of Biosimilars, NORD On Patient Engagement
Executive Summary
News and views from day three of the BIO International Convention: Merck’s Frazier champions both social justice and capitalism; Sandoz’s Pike thinks refinement of clinical data requirements will encourage biosimilar sponsors to target more moderate-selling biologics; National Organization for Rare Disorders’ Salstonstall sees impact from FDA reviewers talking to patients.
Frazier Says Merck Is About Trying To Find The Right Balance
Kenneth Frazier often starts the day perusing the obituary page in the New York Times. When asked during a fireside chat at the BIO International Convention in Philadelphia on 5 June what he’d like his Times obituary to say, the Merck & Co. Inc. chairman and CEO said he hoped he’d be mostly remembered as someone who cared about social justice.
Earlier in the talk, however, Frazier also said “we have to defend capitalism in this world,” a remark that drew applause.
Much of the chat centered on the competing concerns for a company developing and marketing life-saving drug therapies, but also needing to deal with access to those therapies for those who need them.
Frazier noted a familiar refrain that some bad actors define the biopharmaceutical industry in the imagination of the general public, but asserted his company tries to find the right balance between profit and access to health care.
“We try to do the responsible things around pricing and around marketing, and I hope we do a better job of that going forward.” – Merck & Co.’s Kenneth Frazier
“Big pharma, right? That’s a code word – don’t trust these people,” Frazier said. “I’ve worked in this industry, including as a lawyer, going back to the 1970s and this industry was referred to then as the ethical pharmaceutical industry. It wasn’t a joke back then.”
But the biopharma industry needs to recognize “a framework of shared values in our society,” he said, adding that “the cost thing needs to be solved.” Frazier drew an analogy between biopharma and the oil, gas and fossil fuels industry, which often cites the vital role of fuels in human development but still comes up against opposition that only sees it as an environmental threat.
“I think the analogy with our industry is we have to find ways of getting these life-saving medicines to the patients who need them without destroying the basis upon which we’re going to go after tomorrow’s medicines,” Frazier said. In other words, defending the duality of capitalism, in that it provides societal advances, but requires the profit motive to drive innovation.
Merck & Co. tries to find a balance by following the science, the exec said. He pointed to Merck’s clinical development of Keytruda (pembrolizumab) and how it decided to use biomarkers to optimize the patient selection in those trials. Initially, he pointed out, Wall Street was not a fan of that strategy.
“They said, ‘Why would you restrict the number of patients who are eligible to receive your medicine? That’s not a good money-making strategy,’” Frazier recalled. “It was, however, from our standpoint the right way to do it, to follow the science to try to understand which people were best suited for the drug, because you want to get the right drug at the right dose at the right time to the right patient.”
The company then followed that strategy with a decision to price Keytruda initially at par with the standard of care. Frazier asserted Merck & Co. could have been justified in pricing higher than SOC therapy because Keytruda offered an improvement. “We try to do the responsible things around pricing and around marketing, and I hope we do a better job of that going forward,” he said.
NORD: Patient Engagement In Drug Approval Process Increasing
In his 21 years at the National Organization for Rare Disorders, Peter Saltonstall has been encouraged to see a continued increase in patient involvement in the development and approval processes for rare disease therapies. A joint effort between NORD and the US Food and Drug Administration showed just how lacking that input was previously, the group’s president told the BIO audience on 4 June.
Passage of the FDA Safety and Innovation Act in 2012 helped the process along, with further momentum from the 21st Century Cures Act of 2016. (Also see "FDA's 21st Century Cures Plan Gives Patient-Focused Drug Development A Boost" - Pink Sheet, 10 Jul, 2017.) “I have seen in my estimation a real commitment to get the patients in the center of the conversation,” Saltonstall said, “to capture patient data and bring that information back to help industry people like yourselves … have real patient input to be able to better develop drugs.”
“We are working with specific review divisions, many of whom you should know when we had our first meetings to talk to reviewers hadn’t had any interactions with patients.” – NORD’s Peter Saltonstall
In 2018, then-FDA commissioner Scott Gottlieb asked NORD to work with agency review staff to make patient input more pervasive in the review and approval process for rare disease therapies. NORD and the agency signed a memorandum of understanding under which they would work together toward that end, Saltonstall said.
“We are working with specific review divisions, many of whom you should know when we had our first meetings to talk to reviewers hadn’t had any interactions with patients,” he explained. They’re reviewing drugs for a patient population but hadn’t spoken to patients, and so what NORD is doing right now is following through on … having meetings with review divisions, bringing in patients and having … the reviewers speak directly with patients about the disease, about their experience.”
Catch Up On Days One And Two:
(Also see "BIO 2019 Notebook: Sharpless On Pricing, Takeda M&A Strategy, FDA Cell And Gene Therapy Staffing" - Scrip, 4 Jun, 2019.)
(Also see "BIO 2019 Notebook: Merck; Out-Licensing Deals; RMAT" - Scrip, 3 Jun, 2019.)
“It’s really interesting some of the things we hear like, ‘As well as the therapy works, I will tell you that it gives me diarrhea.’ It’s an issue,” Saltonstall added. “And the reviewers are going, ‘Wow, we didn’t hear about that.’”
Now, the FDA is helping NORD obtain funding for longitudinal natural history studies of rare diseases that lack approved drug therapy, he said. These will supply patient-reported data to help reviewers understand the risk/benefit profile of investigational drugs.
Future Biosimilars Could Target More Modest-Selling Biologics
An easing of regulatory expectations for extensive Phase III comparability trials could spur biosimilar sponsors to go after more modest-selling reference biologics, a Sandoz International GMBH executive believes.
The first wave of 351(k) sponsors in the US targeted multi-billion dollar blockbusters – such as AbbVie Inc.’s Humira (adalimumab) and Amgen Inc.’s Enbrel (etanercept) – in part because development costs, including substantial analytical programs and large Phase III trials to demonstrate biosimilarity, can reach into the hundreds of millions of dollars, Julia Pike, VP of intellectual property-North America, told a 3 June panel discussion on biosimilars at BIO.
“I think in the next wave one of the things you’re going to see people press on a little bit harder is how to get something approved as a biosimilar without having to engage in large-scale, Phase III clinical trials,” she said.
“That’s then going to change the kind of candidates that biosimilar companies are going to look at developing. If you don’t have to invest $150m in order to develop a product, then you no longer need that to be a $12-$13bn worldwide blockbuster. You can go after something that just crossed the half-billion mark and still have it be a worthwhile investment.”
“If you don’t have to invest $150m in order to develop a product, then you no longer need that to be a $12-$13bn worldwide blockbuster.” – Sandoz’s Julia Pike
Global health regulators’ familiarity with biosimilars has increased enormously in the past decade, Pike said. “The regulatory agencies have developed a pretty high degree of sophistication with how to think about biosimilars, and as they become more sophisticated you see that they’re refining their guidance of what it takes to be considered a biosimilar.”
“One of the clearest culminations” of this refinement is the US FDA’s November 2018 licensure of Coherus BioSciences Inc.'s Udenyca (pegfilgrastim-cbqv), a biosimilar to Amgen’s Neulasta (pegfilgrastim), which was approved “without substantial Phase III clinical data,” Pike said.
Coherus conducted its clinical program only in healthy subjects, opting not to perform an efficacy or immunogenicity study in oncology patients. (Also see "Keeping Track: FDA Starts November With A Bang" - Pink Sheet, 2 Nov, 2018.)
In contrast, Mylan conducted a safety, efficacy and immunogenicity study in 194 breast cancer patients to support the approval of Fulphila (pegfilgrastim-jmdb), which the FDA approved as the first biosimilar to Neulasta in June 2018. (Also see "Mylan’s Fulphila: First Neulasta Biosimilar’s Road To US Market Slowed Only By Product Quality, GMP Deficiencies" - Pink Sheet, 7 Nov, 2018.)
The initial reference biologics targeted by biosimilar developers were “low-hanging fruit, and the calculation was the biggest products with patents either expiring or expiring soon,” said Paul Golian, VP & assistant general counsel at Bristol-Myers Squibb Co. Given the initial investment for biosimilar development and regulatory uncertainty as the pathway was being established, “it’s not surprising perhaps that so many of the players all went after the same handful of things.”
However, Golian has his doubts about whether the blockbuster category of PD-1/PD-L1 inhibitors – including Merck & Co.'s Keytruda (pembrolizumab) and Bristol’s Opdivo (nivolumab) – will be the focus of biosimilar development given the glut of ongoing new product development efforts in the space.
“There’s actually 151 … PD-1 or PD-L1 molecules in the clinic, or approaching the clinic … and just the big eight companies in this space have more than 2,500 clinical studies. My company has around 860 ongoing clinical studies with our Opdivo product,” Golian said.
Although the currently marketed products are still fairly new and have a lot of patent life left, “rather than biosimilars I think it’s almost like a strategy to just have a me-too, to have yet another antibody” establishing that they are “similar enough that maybe health authorities will start to extrapolate indications,” he said. “There’s a lot of companies big and small that are all
Philly Loves Its Cheesesteaks …
That most quintessential of Philadelphia foods, the cheesesteak, has been front and center at the annual BIO meeting.
During the exhibitor hospitality receptions on 4 June, sandwiches of thinly sliced and diced beef and gooey cheese were available in abundance on the exhibit floor.
At the nearby Reading Terminal Market (billed as “one of America’s largest and oldest public markets housed since 1893 in a National Historic Landmark building”), the lunchtime lines are long at the cheesesteak vendors.
At the start of a 5 June panel discussion on the International Pricing Index, moderator Patrick Kilbride, senior VP of the Global Innovation Policy Center and a Philadelphia area native, had this advice: “If you haven’t tried your cheesesteak yet, I highly recommend Billy Murphy’s Irish Saloon in East Falls. You won’t go wrong.”
Before his BIO fireside chat on 4 June, FDA acting commissioner Ned Sharpless visited the agency’s Philadelphia field office and laboratory. He tweeted a picture of his lunch – a cheesesteak, naturally.
… And Its Beer
Fortunately, the glitterati of the biotech world have plenty of opportunities to wash down those cheesesteaks with a cold beverage.
The BIO convention is running concurrently with Philly Beer Week, a 10-day festival to celebrate Philadelphia as “America’s Best Beer-Drinking City,” according to the event’s organizer. Featured events include beer-focused happy hours, dinners, trivia contests and bingo.