Jared Kaltwasser

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The passage of the Biologics Price Competition and Innovation Act (BPCIA) a decade ago was supposed to usher in a new era: High-priced biologic drugs would have competitors, called biosimilars, that were just as safe and effective. This price competition would then drive down healthcare costs.

In actuality, just as the broader ACA continues to be tied up in court battles, the biosimilars market has been hobbled by legal wrangling. Although the BPCIA was just one provision of the ACA, biosimilars were seen as one of the surest market-oriented ways to reduce healthcare costs.

Optimists see hope in the growing number of FDA-approved biosimilars. Their less-sunny counterparts, however, see unfulfilled potential and a gap between the number of approved biosimilars and the number on the market.

Biologics — agents derived from living organisms rather than chemicals — date back to the beginning of the 20th century. But recombinant DNA technology developed in the 1970s and 1980s launched a new era: synthesized biologics
instead of animal-derived agents. The price tags on some of the biologics were in the tens of thousands of dollars, which, at the time, seemed expensive.

The BPCIA created an accelerated pathway for drugmakers to gain approval for products that were substantially similar to existing biologics. Unlike small-molecule generics, biosimilars are not exact copies of their reference products. A small-molecule drug may comprise a couple dozen atoms; a biologic, hundreds or thousands. The chemical processes used to make small-molecule drugs ensure an exact copy (although the inactive ingredients to make the pill that contains the drug may differ). The fact that biologics are derived from living organisms also adds some slight — but not necessarily meaningful — variability.

Christine Simmon, executive director of the Biosimilars Council, a group that lobbies for the industry, says that although biosimilars are costly to produce, they offer enormous potential to lower prescription drug costs. “(Biosimilars) represent a tremendous savings opportunity for patients and taxpayers,” she says. “We are seeing ... up to 30% discounts now with biosimilars that are on the market.”

The FDA has approved 28 biosimilars so far. The first, approved in 2015, was Sandoz’s Zarxio (filgrastim-sndz), a biosimilar of Amgen’s cancer drug Neupogen (filgrastim). Zarxio came on the market just six months after approval, but most other biosimilars have not had such a quick journey. Seventeen of the 28 approved biosimilars were on the market at the beginning of July, so the gap is narrowingbut still there. 

The approved, on-the-market biosimilars include a handful of Genentech’s chemotherapy drug Herceptin (trastuzumab), as well as biosimilars of Amgen’s bone-marrow stimulant Neulasta (pegfilgrastim) and Janssen Biotech’s immunosuppressant Remicade (infliximab). Six biosimilars for AbbVie’s Humira (adalimumab) have also been approved, dating back to September 2016, but none have yet made it to market.

Simmon says the Humira biosimilars and others aren’t on the market because of litigation brought by the makers of the reference products on which the biosimilars are based. As the costly lawsuits drag out, they extend market exclusivity for the higher-cost brand-name products. Critics, however, charge that the lawsuits are based less on valid legal objections and more on a fear of competition.

Simmon says one way that brand-name drugmakers seek to protect market exclusivity is by filing and defending copious patents. “It’s very common for a brand-name biologic manufacturer to obtain as many patents as possible,” she says, noting that the patents often cover things far beyond the underlying biologic, even extending to language on product labels.

In the case of Humira, AbbVie’s legal strategy prompted a grocer’s union to file a class-action lawsuit arguing that the biopharmaceutical company is unfairly using a “legal thicket” to prolong its monopoly. AbbVie, however, has reached settlement agreements with all of its potential competitors to preserve Humira’s market exclusivity until at least 2023. 

In resolving the final such lawsuit last year, AbbVie’s chief legal officer, Laura J. Schumacher, said the company’s patents fund innovation. “As an innovation-driven biopharmaceutical company, we will continue to develop novel cures for the toughest health challenges and rely on a robust patent system to protect that investment in innovation,” she said in a press release.

Reference product manufacturers have also sought to limit the impact of biosimilars once they eventually reach the market, according to Ameet Sarpatwari, J.D., Ph.D., an assistant professor at Harvard Medical School. “One strategy originator manufacturers have employed to limit biosimilar uptake has been to negotiate formulary exclusivity with payers,” wrote Sarpatwari and his co-authors in an article about biosimilars not living up to their promise published in the August 2019 

American Medical Association Journal of Ethics

Such deals often include rebates for payers or PBMs that essentially create an incentive structure that keeps higher-priced products on the market. That, in turn, has the effect of reinforcing physician comfort with the brand-name drugs, wrote Sarpatwari.

Insurers and PBMs have questions about how the biosimilars market will eventually shape up, Simmon says. A physician can prescribe the generic of a small-molecule drug and know that no matter who the manufacturer is, the generic will almost certainly be available at the pharmacy and will work the same way as the reference product. Will the same be true of biosimilars? “Plans and PBMs, generally speaking, have questions about whether or not there will be a lot of interchangeable biosimilars in the future, as well as ... how much growth we can expect in the availability of biosimilars,” she says.

For Simmon, one priority is avoiding lengthy court battles. She wants to preserve the opportunity for drug companies to enter into patent settlement agreements, which offer a way to quickly legal disputes. She also wants to see patent disputes go through the inter partes review process before the Patent and Trademark Board, an adjudicative body within the U.S. Patent and Trademark Office, rather than get ensnarled in protracted court cases.

Also on Simmon’s wish list is patent reform that puts limits on what can be patented. Finally, she says, the FDA needs to find a better way for interested parties to locate relevant patents — without having to hire costly law firms. “Right now that’s very time-consuming and expensive,” she says, “because there is no resource you can just search through and find patents.”

Additionally, America’s Health Insurance Plans (AHIP) is asking lawmakers to reduce the patent life for biologics from 12 years to seven, arguing that doing so would facilitate earlier availability of biosimilars and further open up the market. Drugmakers are opposed, saying they need a long period of exclusivity to earn back their investment and that it serves the larger purpose of encouraging biotech innovation.

Although it’s clear that biosimilars are here to stay — hundreds remain in development — such regulatory changes could be the deciding factors in when biosimilars finally achieve acceptance and realize their potential in this, their second decade.

Jared Kaltwasser is a healthcare reporter based in Iowa.

Articles

Advocates say a number of regulatory changes could help bring more of these products on to the market.

Is the Biosimilars Waiting Game Finally Over?  

The evidence linking to depression, particularly major depressive disorder, and to healthcare utilization and higher spending is broad and deep. 

But new research findings show that at least some of the spending could be reined if physicians and hospitals targeted some major clinical manifestations of major depressive disorder, such as suicide attempts and treatment failures.

The research, by corresponding author Amy Tung, PharmD, MS, of Allergan Inc., and colleagues, was scheduled to be presented at the Academy of Managed Care Pharmacy’s 2020 annual meeting. The in-person event was canceled because of the COVID-19 outbreak, but presentations and abstracts were presented instead and published as a supplement to the Academy's journal. You can see that supplement 

Tung, who is the associate director of health economics and outcomes research at Allergan, and her colleagues looked at administrative healthcare claims from an unnamed large insurer. The investigators sifted through the data to identify patients between the ages of 18 and 64 who were diagnosed with major depressife disorder between 2012 and 2018 and were prescribed an antidepressant. A total of 29,335 patients were identified for the study.

The records of the cohort were then examined to calculate total healthcare resource use (HRU), and then the independent effect on HRU of events such as MDD-related emergency room (ER) visits, suicide attempts/ideation, severe mental health disorder, and treatment failure.

The analysis found, not surprisingly, that all of the key events were associated with higher levels of HRU, which was expressed in terms of visits to a healthcare facility (inpatient, outpatient, and ER).

The events with the greatest impact on average per-patient HRU were severe mental health disorders, which were associated with 10.25 HRU visits compared with 7.75 visits for those patients without severe mental health disorders. Hospitalization for major depressive disorder (9.39 vs. 7.76 visits), ER visits related to major depressive disorder (9.37 vs. 7.76 visits), suicidal ideation/attempt (9.27 vs. 7.75 visits), and the failure of at least two treatments (8.28 vs. 7.43 visits) were also found to be associated with HRU.

A similar effect was found when those HRU datawere translated into all-cause healthcare spending. The largest spending disparity came when patients had severe mental health disorders ($12,337 vs. $7,513) and hospitalization related to major depressive disorder ($12,156 vs. $7,499). Suicide ideation/attempt raised all-cause spending by nearly $3,000 ($10,496 vs. $7,499). ER visits and treatment failure similarly had notable, though, smaller impacts.

These finding come against a backdrop of a growing recognition of depression’s influence on healthcare utilization and spending. A study published last in the 

 found that spending on major depressive disorder rose by 21.5% between 2005 and 2010. That study also showed that people with serious depression shoulder heavy economic burdens beyond healthcare spending, including more missed days of work and higher overall work productivity impairment. That study concluded that the more severe a patient’s depression, the higher the economic burden associated with that patient.

In their new analysis, Tung and colleagues argued that one important strategy to address the high HRU and spending associated with patients with major depressive disorder would be to better treat or prevent costly key events.

“New MDD therapies that treat patients in the ER or the hospital or prevent suicide attempt/ideation, severe mental health disorder, and treatment failure have the greatest potential to reduce overall MDD costs,” they concluded.

Patients with major depressive disorder have higher healthcare utilization rates when they experience certain key clinical events, according to a new study.

Key Events Drive Significant Portion of Association Between Depression, Healthcare Utilization and Cost

Patients with multiple sclerosis (MS) who are taking alemtuzumab (Lemtrada) may have milder symptoms when infected with coronavirus disease 2019 (COVID-19), according to a small study of 10 patients with relapsing-remitting MS. The study offers new data on what is a complicated question for physicians: How to best treat patients with MS given concerns that some 

 (DMTs) might render patients more susceptible to COVID-19.

Kathleen Costello, MS, ANP-BC, MSCN, associate vice president for healthcare access at the National Multiple Sclerosis Society, noted that 

 recommend patients with MS who are taking DMTs continue taking those treatments, but added that physicians and patients need to be vigilant. "Those people on certain DMT’s that deplete immune system cells should be vigilant with precautions to reduce the spread of the virus, such as wearing a mask in public, frequent and thorough handwashing, social distancing, and avoiding crowds or large gatherings," she said.

, M.D., Ph.D., and colleagues noted that there was a lack of consensus about DMTs in the earliest days of the pandemic. Some guidelines suggested temporarily delaying treatment with immunosuppressive DMTs, particularly if the DMT in question was associated with depletion of lymphocytes. The fear was that such patients would be left more vulnerable to COVID-19.

To investigate the question, Matias-Guiu and colleagues at the Hospital Clínico San Carlos in Madrid telephoned 10 patients with RRMS and asked them questions about their MS, as well as questions about potential COVID-19 symptoms and potential symptoms among members of their households. 

Of the 10 patients included, 80% were female and the mean time since diagnosis was 17.3 years ± 8.59 years). The average time since the last dose of alemtuzumab was 9.8 ± 6.64 months, and the last lymphocyte count was 760 ± 231/μL.

Two of the patients had symptoms such as fever, diarrhea, and headache that the authors believed were likely associated with COVID-19. Neither patient had been evaluated by RT-PCR, though one patient later had a positive serological test. However, neither required hospitalization, and both patients’ symptoms were generally categorized as mild and the length of symptoms appeared to be short. The authors also noted that another participant lived with someone who had contracted COVID-19, and yet that participant did not show any symptoms of the disease.

“Although there are few cases, the feeling is that patients who are under treatment with alemtuzumab do not have different risk than the population,” Matias-Guiu told 

In the study, he and colleagues suggested the apparent lack of a heightened risk might be because immune reconstitution sparked by alemtuzumab might make the patient’s immune system stronger against SARS-CoV-2, the virus that causes COVID-19.

Matias-Guiu said his team has another article, currently under review by a journal, which affirms these findings, though he said the confidence intervals remain very wide due to the low number of cases.

Matias-Guiu said it’s still very early and the data that exists are mostly based on small or short-term studies. He said a number of questions and potential explanations still need to be evaluated. For one, he said the fact that MS patients don’t appear to be at a higher risk of infection than the general population may be unrelated to the disease itself and instead be a result of these patients being less exposed to the virus. For now, though, he said early fears have not been supported by the data.

“Obviously, more studies will come out, but in any case, it does not seem that there should be an additional fear [about MS patients taking DMTs] to that of the rest of the population,” he said.

Are patients with MS taking DMTs at higher risk of infection or case severity during COVID-19? A small study suggests that may not the case with one.

Do DMTs Increase the Risk of COVID-19 for MS Patients?

An increase in molecular testing of patients with gastrointestinal stromal tumors (GIST) would allow physicians to make better therapeutic decisions without a significant uptick in the cost of care, according to a new analysis.

The research found that increasing molecular testing rates to 100% among patients with 2 mutation types would result in an overall cost increase of just $15,213 per million members of a managed care plan per year. That breaks down to just 1.5 cents per member, per year, wrote corresponding author 

, M.P.H., of the Analysis Group economic consulting firm.

The research was set to be unveiled at the 

Academy of Managed Care Pharmacy’s 2020 annual meeting

. The in-person event was canceled because of COVID-19, but the research was posted online instead.

Over the past two decades, investigators have learned how to fine-tune therapy for patients with GIST by matching them with therapeutic strategies tied specifically to the mutations behind their cancers. Yet such “precision medicine” is far from universal. “The use of molecular diagnostics to classify GIST has been shown to be successful in optimizing patient treatment, but these methods remain under-utilized,” wrote 

, M.D., of the Oregon Health and Science University and his co-authors in a 

Proudman and colleagues decided one way to encourage more physicians to follow molecular testing guidelines would be to calculate the costs of including the testing in a patient’s care. To do so, he and colleagues set up a cost-impact model looking at how universal (100%) molecular testing of patients with GIST associated with mutations of 

 exon 9 would affect the overall cost to insurers. At present, an estimated 60% of patients with 

 exon 9 mutations undergo molecular testing, and just 49% of those with 

The model assumed that patients with other types of mutations, and those for whom testing was not performed, received the standard therapy of imatinib (Gleevec) 400mg. Those with 

 exon 9 mutations were assumed to receive a higher, 800 mg dose of imatinib in the model. Those with 

 exon 18 mutations were modeled based on receiving best supportive care, since an effective therapy has yet to be found for patients with the most common of these mutations.

The model assumed the bulk of patients (69%) were on commercial insurance plans; the remaining patients in the simulation were assumed to be on Medicare (23%) and Medicaid (9%). The rate of GIST cases in the study was set at 11 per million members.

As noted above, increasing molecular testing rates to 100% for these patients increased the cost per million members per year by just more than $15,000. Within that number were a mix of increased and decreased costs. Testing costs increased by $2,748, but adverse event costs were $293 lower.

The main influence of the overall increased cost were pharmacy costs, which rose $12,758. Proudman and colleagues said the higher pharmacy costs were due to higher dosages among patients with 

 exon 9 mutation, as well as increased duration of therapy for those patients because of longer progression-free survival. If patients with 

 exon 9 mutations were excluded, overall costs would actually drop slightly due to the decision to treat patients with 

 exon 18 mutations with best supportive care instead of the standard 400 mg dose of imatinib.

Proudman and colleagues said the cost increases were minimal regardless of plan type.

“Increased molecular testing in GIST is associated with minimal additional costs and a meaningful increase in the number of patients receiving optimized treatment,” Proudman and colleagues concluded.

Researchers cost-impact model calculates the cost to be 15 centers PMPY.


Author | Jared Kaltwasser

Articles

Is the Biosimilars Waiting Game Finally Over?

Key Events Drive Significant Portion of Association Between Depression, Healthcare Utilization and Cost

Do DMTs Increase the Risk of COVID-19 for MS Patients?

Boosting Molecular Testing in Patients with GIST Would Have Minimal Cost Impact, Study Finds