Lilly follows Gilead, Mylan lead with authorized generic play

Eli Lilly’s plan to sell a discounted copy of its top-selling insulin illustrates the motivations behind a branded drugmaker strategy to launch generics to their own blockbuster therapies.

The pharma’s decision follows similar moves from Mylan and Gilead Sciences to produce cheaper copies of their own drugs. All three did so amid political and public criticism over pricing and access to their products.

Perhaps the biggest motivator for pharma to take this unorthodox approach is to protect market share from looming competition, Rita Numerof, president of the consulting firm, Numerof & Associates, said in an interview.

Holding onto customers via a lower list price is preferable, even if authorized generics essentially “cannibalize your own products before your competition does,” said Numerof, who has advised companies across the healthcare system for more than two decades.

Launching a branded generic at a reduced price also can help to fend off criticism around drug pricing. Numerof said both factors were at play in Lilly’s decision, and the low-cost version of Humalog could serve to blunt some criticism of the company on that front.

The rationale behind authorized generics, which are produced identically to the approved branded drug, can be seen in how company execs describe such launches.

In public statements, drugmaker execs have emphasized the impact on lowering out-of-pocket patient costs and addressing pricing scrutiny. But the financial drivers still play a role and are a component of how the companies sell the strategy to investors.

Lilly CEO David Ricks wrote in a blog post he hopes the company’s authorized generic will be a “catalyst for positive change across the U.S. health care system,” adding in common industry arguments around the rise of high-deductible health plans and a rebate system that doesn’t fully benefit patients.

But with a March 2020 deadline approaching for a regulatory opening to biosimilar versions of insulin, Lilly also stands to gain an early-mover advantage in the copycat space. Lilly’s Humalog already faces competition from a follow-on biologic developed by Sanofi, which launched the drug last year.

Holding onto market share was also a goal in other recent examples of authorized generic introductions.

Gilead Sciences launched its own set of authorized generics at the beginning of 2019 for its hepatitis C drugs, Harvoni and Epclusa. And while then CEO John Milligan played up the plan when announced last September as a lower-priced alternative for patients, the market dynamics suggest other reasons for the company, too.

On the biotech’s fourth quarter earnings call last month, chief financial officer Robin Washington called the authorized generics part of the plan to maximize the company’s opportunity in the hepatitis C market, adding the launches “should keep us very competitive in a durable long-term market.”

Sales of those two drugs has fallen in recent quarters as fewer untreated patients begin antiviral treatment, and competition cuts into pricing. The cheaper generic could help Gilead reach Medicaid and Medicare patients that previously didn’t see as much of a benefit from rebates that the company gives insurers on its list prices.

In another example, Mylan announced in December 2016 an authorized generic for its blockbuster EpiPen treatment. The copy of the auto-injector launched at a wholesale acquisition cost of roughly half the branded drug-device combination.

Again, company CEO Heather Bresch then called it “decisive action” to give Americans a solution to the problem of rising drug prices, while eliding Mylan’s direct role in raising EpiPen’s wholesale cost.

A few months before that launch, Congress grilled Bresch over a recent set of hikes to the allergy treatment’s list price.

In Lilly’s case, Sen. Chuck Grassley, R-Iowa, called the decision “good news” in a Monday tweet, but added it’s only one piece of the puzzle on insulin, with more to be done. The Finance Committee chairman also reiterated his expectation for thorough responses to a recent inquiry sent by him and Ron Wyden, D-Ore., to insulin drugmakers.

Looking forward, Numerof predicted the industry will see more authorized generic launches as part of an industry response to pricing scrutiny.

https://www.biopharmadive.com/news/lilly-follows-gilead-mylan-lead-with-authorized-generic-play/549760/

Fewer Complications With Robotic Surgery in Early Endometrial Cancer

Target Audience and Goals:

Gynecologic oncologists, obstetricians/gynecologists, primary care physicians, surgeons, internists

The goals of the study were to determine whether minimally invasive robotic surgery (MIRS), approved for treating gynecologic conditions in Denmark in 2005, reduced rates of serious complications in women with early-stage endometrial cancer, and whether the introduction of MIRS increased the overall use of minimally invasive surgery (MIS) in this setting.

Questions Addressed:

• Did the national introduction of MIRS in Denmark reduce the primary outcome of severe complications, defined as 30-day mortality and any intraoperative and post-operative complications in patients with early-stage endometrial cancer?
• How did complication rates compare among those treated with minimally invasive laparoscopic surgery (MILS), MIRS, and laparotomy?
• What was the rate of increase of MIRS in Denmark after its introduction?

Study Synopsis and Perspective:

MILS for endometrial cancer has been associated with reduced complication rates compared with total abdominal hysterectomy in a number of randomized trials, but the uptake of MILS was not rapid in Denmark before the introduction of robotic assistance.

After the introduction on a nationwide basis in Denmark in 2005, MIRS was associated with the performance of a greater proportion of MIS, as well as lower serious complication rates than laparotomy in patients with International Federation of Gynecology and Obstetrics stage I or II endometrial cancer, according to researchers led by Siv Lykke Jørgensen, MD, of Odense University Hospital in Denmark.

In Denmark, the treatment of early-stage endometrial cancer was centralized from 28 centers to 6 national cancer centers starting in 2005, each of which implemented MIRS from 2008 to 2013. The authors believe that this centralization produced a high flow of patients and “optimal conditions for improving surgical expertise.”

As the use of MIRS rolled out across the country, the rate of total abdominal hysterectomy dropped from 85.9% to 27.8%, while MIS increased from 14.1% to 72.2% (MILS 22.2%, MIRS 50.0%), the authors reported in JAMA Surgery.

The research team defined serious complications as 30-day mortality, and severe intraoperative and postoperative complications. Severe intraoperative complications included unintended vascular, urinary tract, bowel, or nerve damage; severe postoperative complications encompassed the 90 days following surgery and included acute renal failure, paralytic ileus, deep venous thrombosis, pulmonary embolism, acute myocardial infarction, sepsis, fistula, postoperative deep or intra-abdominal hematoma, surgical evacuation of cavities, and the need for gynecologic reoperation.

The nationwide registry study included 5,654 women with early-stage disease who underwent surgery from January 1, 2005 to June 30, 2015. These women were divided into two groups:

• Group 1 included 3,091 women who underwent surgery before the introduction of MIRS in their regions
• Group 2 included 2,563 women who underwent surgery after the introduction of MIRS

In group 1, 7.3% had severe complications compared with 6.2% in group 2. In multivariate logistic regression analyses, women in group 1 were found to have a significantly greater risk of developing complications compared with women in group 2 (OR 1.39, 95% CI 1.11-1.74).

In group 2 — those in the post-MIRS period — severe complications occurred in 81 of 712 women who underwent total abdominal hysterectomy (11.4%), 29 of 569 women who underwent MILS (5.1%), and 59 of 1,282 women who underwent MIRS (4.6%). In this group, total abdominal hysterectomy was associated with increased odds of complications compared with either type of MIS:

• MILS (OR 2.58, 95% CI 1.80-3.70)
• MIRS (OR 3.87, 95% CI 2.52-5.93)

No significant difference was seen in complication rates between MILS and MIRS (OR 1.50, 95% CI 0.99-2.27).

The researchers found that the odds of severe complications were associated with lymphadenectomy in group 2, as well as American Society of Anesthesiologists (ASA) score, body mass index, socioeconomic status, and surgical year, but not with age, smoking status, tumor risk group, socioeconomic group, and intra-abdominal adhesions.

Strengths of the study included prospectively entered national data over a 10-year period with the gradual introduction of MIRS. By dividing the subjects into cohorts according to the availability of MIRS, researchers noted that they avoided a comparison across surgical modalities that were not available during the time frame. The study also included 97% of women who had surgery for early-stage endometrial cancer in Denmark, minimizing selection bias.

Limitations of the study included the risk of information bias, which is inherent in registry-based studies. As there may have been an underreporting of minor complications in the registry, the authors included only major complications. The authors were unable to adjust for surgeon-specific learning curve, as information on MILS and MIRS experience of surgeons was not available, though they noted that the MIRS learning curve is reported to be less steep than that of conventional laparoscopy.

Source References:

JAMA Surgery, 2019; DOI: 10.1001/jamasurg.2018.5840

Editorial: JAMA Surgery, 2019; DOI 10.1001/jamasurg.2018.5841

Study Highlights: Explanation of Findings

MIRS was approved for treatment of gynecologic conditions in 2005 in Denmark and rolled out across the nation starting in 2008. Jørgensen and colleagues noted that their data suggest that the implementation of MIRS increased the use of MIS overall and reduced the risk of complications compared to open surgery.

This may be the first analysis of how a nationwide uptake of MIRS affected the risk of surgical complications in an unselected national cohort of women with early-stage endometrial cancer, the authors noted. “The reduction in the number of severe complications was observed despite a higher proportion of women with an older age, a high ASA score, high-risk histopathologic characteristics, and intra-abdominal adhesions being offered MIS and a higher proportion of women undergoing staging lymphadenectomy,” they wrote.

Randomized trials comparing total abdominal hysterectomy vs MIRS have also shown a reduced risk of complications post-MIS, but not all studies have confirmed this, according to Jørgensen’s group, with one U.S. study of Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data showing a rate of 23.7% with MIRS vs 19.5% with MILS. “However, we believe that the increased risk of complications after MIRS compared with MILS is a result of selection bias related to the allocation of women with a higher risk of complications to undergo MIRS rather than to the higher risk of complications after MIRS.”

In a commentary that accompanied the study, Jason D. Wright, MD, of Columbia University in New York City, and colleagues, wrote that the study “demonstrates that minimally invasive hysterectomy is associated with fewer complications than laparotomy and that increasing use of MIS improves surgical outcomes.”

However, the commentary stated, the question remains whether a robotically assisted surgical program is required to increase the use of MIS. With that question in mind, they noted that the study comes with several caveats, including the fact that there was no true control group, and that the results could have been confounded by the fact that endometrial cancer care was centralized into six regional cancer centers in Denmark at the time robotically assisted surgery was being introduced.

“Regardless, Jørgensen and colleagues have demonstrated that increasing the rate of minimally invasive hysterectomy can improve outcomes for women undergoing hysterectomy for early-stage endometrial cancer,” Wright’s group concluded. “Going forward, the use of MIS for early-stage endometrial cancer should be an important quality metric. Programs to promote access to MIS, whether laparoscopic or robotically assisted, should be a priority for women with endometrial cancer.”

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Heidi Wynn Maloni, PhD, ANP-BC, CNRN, MSCN, Nurse Planner

Primary Source

JAMA Surgery

Source Reference: Jørgensen S, et al “Nationwide introduction of minimally invasive robotic surgery for early-stage endometrial cancer and its association with severe complications” JAMA Surg 2019; DOI: 10.1001/jamasurg.2018.5840.

Secondary Source

JAMA Surgery

Source Reference: Wright J, et al “Harnessing minimally invasive surgery to improve outcomes in endometrial cancer surgery: The robots are coming” JAMA Surg 2019; DOI: 10.1001/jamasurg.2018.5841.

Additional Source

MedPage Today

Source Reference: Bassett M “Fewer Complications With Robotic Surgery in Endometrial Cancer” 2019.

https://www.medpagetoday.org/hematologyoncology/othercancers/78379?_ga=2.167776808.827601334.1551534165-1125047970.1528569052

Glooko makes its management app free to any person with diabetes

Glooko has made its mobile app free for any person with diabetes, ditching the subscription fees that had applied to users who were not sponsored through their provider, health plan or employer.

The move comes on the heels of announcements promising that the 2015 Fierce 15 company’s product will be compatible with platforms such as Senseonics’ implantable, long-term continuous glucose monitoring hardware, as well as the upcoming connected insulin pens from Novo Nordisk.

While one-time hardware costs may still apply, Glooko’s free version will include all the previously available features, including helping users track their glucose levels and spot trends connected to synced food, exercise and medication data. It also allows healthcare providers to check in and monitor progress remotely.

“I am thrilled we are removing the subscription fee for users of the mobile app—this will allow anyone who wants to use Glooko for self-management to be able to do so,” CEO Russ Johannesson said in a statement, adding that it will also allow providers to monitor larger patient populations. “Diabetes is a very complicated, data-intensive condition; more frequent support for patients is critical in helping them better manage their diabetes.”

According to the company, its remote monitoring programs have been shown to help improve average blood glucose outcomes by 12%, after three months of patient coaching, and helped reduce hyperglycemia events by 15%.

For users of Senseonics’ 90-day Eversense CGM system—launched in August of last year—logged blood glucose, insulin, food intake and other data will be shared with Glooko after connecting their Eversense account in the cloud, the company said in a statement.

“Glooko has a large database of millions of users who are now able to see a clearer picture of their glucose profiles by integrating Eversense CGM data,” said Senseonics President and CEO Tim Goodnow. “With personalized medicine at the forefront of healthcare, data integration between Eversense CGM and Glooko helps provide customized data for users as well as healthcare providers.”

https://www.fiercebiotech.com/medtech/glooko-makes-its-management-app-free-to-any-person-diabetes

Diabetes coverage better, but shake-up on the way with Novo’s oral semaglutide?

Payer pressure has been squeezing diabetes drugs, leading to some major sales difficulties and layoff rounds. As Bernstein analyst Wimal Kapadia observes, things are on the mend in terms of 2019 formulary coverage, but one drug could “disrupt them all.”

Most diabetes drug classes “fared much better than we would have anticipated,” Kapadia wrote in a Tuesday report to clients. Other than fast-acting insulins, all classes saw an uptick in 2019 formulary coverage, he said.

Novo’s Tresiba is driving a coverage improvement for the basal insulin class, Eli Lilly and Novo are competing in the GLP-1 field, and Merck & Co.’s Januvia and Lilly and Boehringer Ingelheim’s Jardiance are winners in their respective DPP-4 and SGLT2 arenas. But Novo’s oral semaglutide could put pressure on all of them, Kapadia contended.

Oral semaglutide will touch on both the branded orals and the injectable GLP-1s and therefore holds power to shake up the coverage landscape. “The payers’ ability to use it as a tool to squeeze in the branded orals and injectable GLP-1s will likely come down to price,” the Bernstein analyst said.

If Novo prices the drug at a small premium to existing orals, payers might use it to drive down other drugs’ costs given its superior efficacy profile. Or, if the drug comes at a high price, Kapadia said he expects “step edits,” where patients will be required to go through cheaper SGLT2s or DPP-4s before moving up to oral semaglutide.

Novo has amassed a large pool of late-stage data for its megablockbuster hopeful. Across the Pioneer trials, oral semaglutide proved better at reducing blood sugar and helping patients lose weight, even when it was pitted against Januvia and Jardiance, or in some cases, against Novo’s own Victoza and Lilly’s GLP-1 rival Trulicity. It has already turned up cardiovascular outcomes data, showing it could cut CV-related death versus placebo.

The Danish diabetes giant had bought a priority review voucher with an eye on an earlier nod, executives revealed during its fourth-quarter earnings call in early February. That could mean a potential approval by the end of the year, ODDO BHF analysts have previously said.

Currently, Novo’s Victoza and Ozempic and Lilly’s Trulicity account for about 86% of GLP-1 volumes, according to Kapadia. Coverage has increased across the board for them—Victoza, plus 8%, Ozempic, up 58%, and Trulicity, 5%—and even AstraZeneca’s extended-release Bydureon BCise saw coverage grow 4% as the British drugmaker shifts patients to the easier-to-use version. It is a remarkable phenomenon “for a class that is the most expensive amongst diabetes products,” the Bernstein analyst noted.

Even though Trulicity still holds the top spot for the second year running with a coverage ratio of 84%, including almost all patients across commercial and 70% in the highest quality tier of Medicare Part D plans, those that allow only Trulicity have decreased, Kapadia noted.

Pricing pressure and cut-throat competition has yet to spread to the GLP-1 franchise at least from a coverage perspective. The “duopoly” is working well for now, as Ozempic’s expansion hasn’t disrupted Trulicity in any major way, but 2020 might be a different story, Kapadia figured.

“With consecutive years of coverage expansion for the class, we would be very surprised if we did not see some tightening in 2020,” he said. Victoza is benefiting from a CV risk-reduction nod in 2017. But last November, Trulicity got its own CV data. In the Rewind study, the Lilly GLP-1 reduced a combined rate of heart attack, stroke and CV death compared with placebo. Because just over 30% of participants had established CV disease, Credit Suisse analyst Vamil Divan at that time argued the data could help Trulicity distinguish from other drugs. Meanwhile, Ozempic is also looking to get pooled CV data onto its label. Both will file ahead of contracting season, Kapadia said.

With all the data Lilly and Novo rolled out to differentiate their products, Kapadia said payers will likely become pickier. “Our take is that payers will almost certainly try to push the market toward a single award,” he wrote. “We suspect that it will come down to price to ensure decent coverage.”

Elsewhere in the diabetes landscape, Tresiba saw its coverage ratio rise 16%, the largest change in the basal insulin category, and it’s now just slightly smaller than Novo’s Levemir. Coverage for fast-acting insulins, including Novolog and Lilly’s Humalog, largely stood still in 2019. Within the stable DPP-4 class, Januvia grew 7%. As for SGLT2s, Kapadia noted a significant change in 2019, when Jardiance’s 19% growth came at the expense of Johnson & Johnson’s Invokana. The two drugs were at the same level in 2018.

https://www.fiercepharma.com/pharma/diabetes-meds-coverage-improves-but-novo-s-oral-semaglutide-could-disrupt-them-all-analyst

Former Agios Executive to Take Over Deciphera After CEO Steps Down

After five years at the reins, Mike Taylor will step down from his role as president and chief executive officer of Waltham, Mass.-based Deciphera Pharmaceuticals. Taylor’s last day in the role will by March 18, the company announced late Monday.

Steve Hoerter, the chief commercial officer of Agios Pharmaceuticals, will take over the top spot of Deciphera. Hoerter has been serving as a member of the company’s board of directors. Taylor will assist Hoerter through the transition for a period of about six months, the company said in its announcement.

Taylor took over the helm of Deciphera in 2014. During his five years as president and CEO, he has guided the company’s oncology pipeline to have to Phase III candidates that could become approved products. In the fall of 2018, Deciphera completed enrollment of the Phase III INVICTUS study f DCC-2618, a broad-spectrum KIT and PDGFRα inhibitor, in fourth-line and fourth-line-plus gastrointestinal stromal tumor (GIST) patients. At the time of the announcement in November, Taylor said the company anticipates the report of top-line data by the middle of 2019. If the results are successful, he said that would support filing a New Drug Application for full approval in fourth-line and fourth-line-plus GIST patients.

The company also initiated a Phase III study in second-line GIST patients who have progressed or are intolerant to front-line therapy with imatinib, including those with any KIT or PDGFRα mutation.

Taylor also oversaw the initial public offering of the company in 2017.

James A Bristol, chairman of the board of directors at Deciphera, touted the work accomplished by Taylor during his time at the helm of the company. Bristol said that since Taylor took over as CEO in 2014, the company has transitioned from an “early-stage private company into a public company with two ongoing pivotal Phase III studies, multiple promising clinical product candidates, and a robust discovery engine.” Bristol noted that Taylor’s departure comes as the company prepares for a potential transition into a commercial-stage oncology company, one that Hoerter will be able to handle.

“Steve’s significant contributions as an existing member of our board of directors give us great confidence that he will be an exceptional CEO who will lead Deciphera to continued success as we seek to become a commercial oncology company,” Bristol said of Hoerter.

Hoerter joins the executive ranks of Deciphera with more than 25 years of global pharmaceutical and biotechnology sales, product launch and general management experience. In addition to his most recent role as CCO of Agios, Hoerter has held senior commercial positions at leading oncology companies including Agios, Clovis, Roche, Genentech, Chiron and Eli Lilly.

“This is an exciting time at Deciphera as we prepare for the read-out of our first Phase III trial of ripretinib and the potential transition to a commercial-stage company. I am honored to succeed Mike as CEO, and to lead Deciphera as we rapidly advance our portfolio of transformative product candidates with the goal of improving the lives of people living with cancer. Together with the great team at Deciphera, I look forward to building on the strong science and patient-focused culture of the company,” Hoerter said.

Taylor noted that he was proud of all that the Deciphera team has accomplished in his five years as CEO. He touted the experience of Taylor and said he will be the “right person” to lead Deciphera into its next phase as a commercial oncology company.

https://www.biospace.com/article/former-agios-executive-to-take-over-deciphera-after-ceo-steps-down/

Ligand sees Q1 revenue ‘at least’ $38M, not comparable to consensus $55.21M

Ligand is providing guidance for the first quarter of 2019 for total revenues of at least $38 million, and adjusted diluted EPS of approximately $30.00. First quarter revenue breakdown is projected to be approximately $19 million in royalties, including $15 million of Promacta royalties estimated for the first two months of 2019, $12 million in license fees and milestones and $7 million of material sales. There is potential for approximately $5 million in additional royalties and contract payments during the first quarter based on the timing of milestones and sales levels for royalty-bearing assets.
https://thefly.com/landingPageNews.php?id=2874705

Voyager Therapeutics initiated at Cantor Fitzgerald

Voyager Therapeutics initiated with an Overweight at Cantor Fitzgerald. Cantor Fitzgerald initiated Voyager Therapeutics with an Overweight and $27 price target.
https://thefly.com/landingPageNews.php?id=2874731