AbbVie’s massive Humira discounts are stifling Netherlands biosimilars: report

Could a drug’s price ever be too low? That’s what some market-watchers are asking in the Netherlands, where AbbVie is discounting Humira as much as 89%.

The De Groene Amsterdammer dug into the procurement process for Humira biosimilars after they launched in Europe last year and turned up aggressive discounts that have effectively held off biosimilar rivals. And some of those would-be competitors have pulled back from the market because of those discounts, the newspaper reports.

At least 70% of Dutch patients remain on Humira, according to the publication. And no wonder: AbbVie struck a discount of up to 89% in one case to retain business for its original biologic.

Those discounts could be a red flag for Humira’s sales outside the U.S. this year, Bernstein analyst Ronny Gal figures. His team had expected ex-U.S. Humira sales to fall 35% this year, “but if that report is indicative of the broader environment, cuts may be much deeper,” he wrote in a note Monday.

In the Netherlands, though, the worry is that AbbVie’s discounting will drive biosimilar makers out of the market. One company has discontinued its version of the megablockbuster, De Groene Amsterdammer reports. Another only counts one hospital pharmacy as a customer in the country. And another company didn’t sell any of its biosimilar after six months of preparation and chose to export its Humira copies. Amgen and Sandoz each have had limited success there, the publication says, despite their powerful marketing muscle.

And at least one expert warns the drugmaker could raise prices if the other biosimilar makers call it quits. After all, AbbVie would have renewed pricing power without those competitors.

“This is a form of ruthlessness that we really only know from the American market,” Arnold Vulto, honorary professor of hospital pharmacy at Erasmus MC, told De Groene Amsterdammer, according to a translation. He called it a form of “market poisoning” and said AbbVie could charge high prices again with a renewed monopoly.

Now, the Netherlands’ competition authority is looking into the procurement process, the publication reports.

In the Netherlands, hospitals join together to increase purchasing power and secure discounts on drugs such as Humira. Each group individually negotiates with pharma companies. In one case, a hospital group disbanded over a disagreement on Humira biosimilars, the publication reports.

Another catch for those considering biosimilars? Each hospital retains an amount of the original drug for patients who are allergic or don’t otherwise benefit from copycats, the publication reports. If a hospital chooses to go with the biosimilar, AbbVie can refuse discounts on the Humira that facility does buy, diminishing the financial incentive for hospitals to switch over to biosimilars.

An AbbVie representative declined to respond to the article’s “claims and speculations,” the publication reports.

Even AbbVie executives themselves have said the competition is fiercer than they expected after biosimilars launched in October. The company lowered its ex-U.S. sales estimates for the drug in 2019 after one quarter of European competition.

Meanwhile, the company has the key U.S. market to itself until 2023 under patent agreements inked with various biosimilar makers. The U.S. made up most of Humira’s nearly $20 billion in global sales last year. As U.S. biosimilar launch dates near, AbbVie hopes new immunology launches Skyrizi and upadacitinib can pick up steam. One Humira biosimilar maker, Boehringer Ingelheim, has chose to hold out and fight its patent arguments in court rather than settle.

And AbbVie can take solace in the fact it’s not the only company to have upset market watchers in the Netherlands. Previously, Dutch health minister Bruno Bruins accused Novartis of exploiting an orphan designation on Lutathera to overprice the drug, which treats certain neuroendocrine tumors. Novartis responded that it “carefully considered” the price and that the price is similar to other drugs for the patients.

https://www.fiercepharma.com/pharma/abbvie-stifling-humira-biosim-competition-massive-discounting-dutch-report

Is Puma off cancer M&A list with Nerlyx marketing deal?

Puma Biotech has been a permanent subject of takeover gossip. But whatever M&A hope investors previously had for a buyout, a European Nerlynx licensing deal may have shattered it.

The Los Angeles biotech is licensing HER2 breast cancer med Nerlynx’s commercialization rights in Europe and part of Africa exclusively to Pierre Fabre for an upfront payment of $60 million, the company said on Monday.

Puma’s stock fell nearly 9% Monday that day on the news. The reason? As analysts from J.P. Morgan, SVB Leerink and Cantor Fitzgerald observed, investors are concerned that the deal reduced the possibility of a takeover.

“While the terms of the deal for this region appear reasonable, we believe some investors may be disappointed with an additional licensing agreement that could further reduce the strategic value of Nerlynx to a potential acquirer,” SVB Leerink analyst Thomas Smith wrote in a Monday note to clients.

In fact, Pierre Fabre is the sixth partner Puma has tapped for Nerlynx marketing, leaving the U.S. and Japan as the only remaining major markets, Smith said. Back in February 2018, the company licensed Greater China rights to CANbridge Life Sciences, right after granting Medison Pharma the Israeli rights. And that’s not to mention that a part of the drug’s sales will go to its original licensor, Pfizer, as royalty payments.

The cancer specialist has been a constant target of M&A speculation dating at least back to around mid-2017 when Nerlynx won an FDA advisory committee recommendation. At first, industry watchers pegged the time after approval and before launch as the perfect time for a takeover.

Nerlynx’s green light, to prevent breast cancer recurrence in women previously treated with Roche’s Herceptin, further fueled the rumor, especially as the label turned out cleaner and broader than expected (i.e., not restricted to hormone-receptor positive patients), despite some questions raised during the AdCom meeting.

“[I]t has long been explicitly clear that there is potential for the company to be acquired, given Nerlynx is an unencumbered oncology asset with >$1B in commercial sales potential,” Cowen analyst Chris Shibutani wrote in July 2017.

But rather than waiting until September as previously expected, Puma immediately launched the drug in the U.S., triggering the interpretation that an acquisition was not imminent. “We’d tend to agree that if a deal was only days or weeks away, it’s hard to understand why the company would push ahead with commercialization,” RBC Capital analyst Matthew Eckler wrote at the time.

In early 2018, the buyout rumor was again revived when a negative EU opinion looked likely. That January, Puma said a negative trend vote from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency would likely translate into a “no” on Nerlynx’s application, scheduled for February.

Puma’s stock took a hit on the news. But Almington Capital president John Engle, in a Seeking Alpha post, maintained that the drug’s U.S. market still represented a lucrative opportunity, and a beat share price made the company look quite attractive for a buyout.

And then, late in the year, GlaxoSmithKline made a $5.1 billion acquisition of Tesaro which, like Puma, had a marketed product—PARP inhibitor Zejula—and a commercial team. The move again stirred up M&A buzz among industry watchers.

Now, a buyout seems unlikely, at least in the eyes of some investors. But after talking to Puma CEO Alan Auerbach, Cantor analysts said that “the likelihood of potential M&A remains about the same.” Management pointed to other companies such as Pharmacyclics and Medivation that did deals in Europe for royalties and were also acquired afterward, according to Cantor.

Meanwhile, based on Pierre Fabre’s existing breast cancer sales team and experience in negotiations with EU payers, Cantor reasoned that “[t]he logic for doing an EU partnership was to get better economics than building a sales force itself.”

https://www.fiercepharma.com/pharma/puma-s-eu-nerlynx-licensing-pact-deals-blow-to-investors-takeover-hope

Stifel: abicipar improvement not enough to make Allergan drug competitive

After Allergan reported data from its 28-week open-label safety study, MAPLE, to evaluate the safety of abicipar produced via a modified manufacturing process, Stifel analyst Annabel Samimy noted that overall inflammation was reduced to 8.9% and severe inflammation to 1.6%. However, her talks with key opinion leading physicians lead her to conclude that the MAPLE inflammation rates are still too high compared to other “extremely safe” and effective options on the market today. Increasing competition on efficacy, dosing length, and price, as well as the still-high inflammation rates, continue to limit any meaningful commercial opportunity for abicipar, said Samimy, who keeps a Hold rating on Allergan shares.
https://thefly.com/landingPageNews.php?id=2887579

Bristol-Myers reports long-term survival results from pooled analyses of Opdivo

Bristol-Myers Squibb announced results from pooled analyses of survival data from four studies in patients with previously-treated advanced non-small cell lung cancer who were treated with Opdivo. In the pooled analysis of the four studies, 14% of all Opdivo-treated patients were alive at four years. Notably, in patients with PD-L1 greater than or equal to1% and less than1%, four-year overall survival rates were 19% and 11%, respectively. In the pooled analysis of the two phase 3 trials, CheckMate -017 and -057, the four-year OS rate for Opdivo-treated patients was 14% compared to 5% for docetaxel-treated patients. Additionally, exploratory landmark analysis of OS found that of patients who had a complete or partial response at six months, 58% of those treated with Opdivo were alive four years later vs. 12% of patients treated with docetaxel. Of patients who had stable disease at six months, 19% of those treated with Opdivo were alive four years later vs. 2% of patients treated with docetaxel. The data were presented at the American Association for Cancer Research Annual Meeting 2019 in Atlanta. Long-term safety data for Opdivo from all four studies were consistent with the known adverse event profile and did not reveal any new safety signals. The discontinuation rate due to treatment-related adverse events was 8.7% in patients treated with Opdivo. The most common treatment-related AE was fatigue. Scott Antonia, M.D., Ph.D., director of the Duke Cancer Institute Center for Cancer Immunotherapy, commented, “These analyses in a large population of patients with previously-treated advanced non-small cell lung cancer show, for the first time, that response to Opdivo correlates to a survival benefit over many years. These long-term survival outcomes are particularly interesting given that, historically, the average five-year survival rate for this patient population is approximately 5%.”

https://thefly.com/landingPageNews.php?id=2887585

Scholar Rock presents additional preclinical data on SRK-181-mIgG1

Scholar Rock announced additional data on the mechanism of action of a highly specific inhibitor of TGFbeta1 activation in syngeneic mouse tumor models that emulate clinically-observed primary resistance to checkpoint blockade therapy. Detailed preclinical results are being presented at the American Association for Cancer Research, or AACR, annual meeting. The preclinical data demonstrate that treatment with SRK-181-mIgG1, a highly specific inhibitor of TGFbeta1 activation, in combination with an anti-PD1 immunotherapy, can drive tumor regression or control, resulting in significant survival benefit compared to anti-PD1 monotherapy, the company said. In addition, newly presented immune response data show that combination treatment leads to infiltration and expansion of CD8+ T cells and a reduction of immunosuppressive myeloid cells, suggesting TGFbeta1’s multiple contributions to primary resistance to CBT. “These new preclinical results reinforce our belief that a highly specific inhibitor of TGFbeta1 activation can enable the immune response to overcome a key mechanism of primary resistance to checkpoint blockade therapy, even in tumors that express other TGFbeta isoforms, and could meaningfully expand the number of patients who could benefit from checkpoint blockade therapies. With the recently announced nomination of SRK-181 as the first product candidate in our cancer immunotherapy program, we are eagerly working towards initiating a Phase 1 trial in patients with solid tumors in mid-2020,” said Nagesh Mahanthappa, President and CEO of Scholar Rock.
https://thefly.com/landingPageNews.php?id=2887591

Jounce Therapeutics reports new clinical data on vopratelimab

Jounce Therapeutics reported new clinical data on vopratelimab at the American Association for Cancer Research Annual Meeting. “The Jounce poster presentations show that patients in the ICONIC trial with emergence of ICOS hi CD4 T cells have improved progression free survival and overall survival compared to patients with ICOS lo CD4 T cells. Data related to important immune characteristics of ICOS hi CD4 T cells were also presented,” said the company. Three groups of Iconic relapsed refractory solid tumor patients were compared in the new analysis: 18 patients who have demonstrated ICOS hi CD4 T cells in the blood, 32 patients who have demonstrated ICOS lo CD4 T cells, and a group of patients enrolled in parts A through D which includes an additional 151 patients that were not tested for ICOS status due to lack of samples, according to Jounce. It added, “The emergence and persistence of the ICOS hi CD4 T cell biomarker in the peripheral blood is associated with improved PFS and OS: All benefit in the study, measured by tumor reductions, PFS and OS, was in the ICOS hi CD4 T cell group; PFS: median 6.2 months for patients with ICOS hi CD4 T cells vs 2 months for both patients with only ICOS lo CD4 T cells and All Patients; OS: median not yet reached for patients with ICOS hi CD4 T cells vs 9 months for patients with only ICOS lo CD4 T cells and 9.1 months for All Patients.” Richard Murray, CEO of Jounce Therapeutics, said, “We are encouraged by the improved PFS and OS data associated with the emergence of the ICOS hi CD4 T cell biomarker and are convinced that meaningful advancements in immuno-oncology will require the type of science-based translational understandings that the Jounce team and platform have enabled to advance vopratelimab thus far. We have established our translational technology base for the purpose of creating a preclinical and, more importantly, clinical scientific understanding of the mechanism of action of new immunotherapies and the characteristics of responding versus non-responding patients to focus the next steps of clinical development for vopratelimab and our pipeline.”
https://thefly.com/landingPageNews.php?id=2887593

EDAP TMS SA Reports Q4 and Full Year 2018 Results

• Record fiscal year 2018 revenues of EUR39.2 million
• Q4 2018 HIFU net sales increased 79% year-over-year
• Profitable and cash flow positive during the fourth quarter of 2018
• Completed first U.S. sale of Focal One at the end of 2018
• Ended the year with a strong cash position of $22.3 million

EDAP TMS SA EDAP, +22.33% (“the Company”), the global leader in therapeutic ultrasound, announced today financial results for the fourth quarter and full year 2018 and provided a strategic and operational update.

Marc Oczachowski, EDAP’s Chief Executive Officer, said: “We are very pleased to report our fifth consecutive year of growth during 2018, achieving total revenue of EUR39.2 million. As announced, one of the major milestones during the year was FDA clearance of Focal One in June, and just six months later, we completed the first U.S. sale of Focal One to the John Wayne Cancer Institute. We followed that up with three additional U.S. Focal One sales in less than sixty days. Our HIFU sales and marketing development teams have also been very active outside of the U.S., with the opening of new markets and further expansion in existing countries such as Brazil.

“We experienced very strong momentum during the fourth quarter in the adoption of our HIFU technology in the U.S. and internationally. Our teams are fully focused on leveraging this positive trend to further develop our sales pipeline for 2019,” Mr. Oczachowski concluded.

https://www.marketwatch.com/press-release/edap-tms-sa-edap-reports-q4-and-full-year-2018-results-2019-04-01