Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosim­i­lars in­dus­try has gen­er­al­ly been a dis­ap­point­ment since its in­cep­tion, with FDA ap­prov­ing 33 biosim­i­lars since 2015, just a frac­tion of those have im­me­di­ate­ly fol­lowed their ap­provals with launch­es. And more than a hand­ful of biosim­i­lars for two of the biggest block­busters of all time — Ab­b­Vie’s Hu­mi­ra and Am­gen’s En­brel — re­main ap­proved by FDA but still have not launched be­cause of le­gal set­tle­ments.

Part of the rea­son that many of these brand-name bi­o­log­ic com­pa­nies have proven suc­cess­ful at block­ing biosim­i­lar com­pe­ti­tion is through their use of patent fortress­es, de­signed to make it im­pos­si­ble, or ex­treme­ly ex­pen­sive, to wage le­gal bat­tle.

In 2018, for ex­am­ple, Ab­b­Vie’s Hu­mi­ra was cov­ered by 132 patents, Roche’s Avastin (which now has biosim­i­lar com­pe­ti­tion) was cov­ered by 86 patents and Her­ceptin (which al­so now has biosim­i­lar com­pe­ti­tion) by 108 patents.

Re­searchers are now un­cov­er­ing the ex­tent to which sec­ondary patents (i.e., not the ones cov­er­ing the ac­tive in­gre­di­ent) have played a ma­jor role in stunt­ing the growth of the biosim­i­lars in­dus­try.

“Among patents as­sert­ed in US biosim­i­lar lit­i­ga­tion, on­ly 6% cov­ered the ac­tive in­gre­di­ent in the bi­o­log­ic drug, while the vast ma­jor­i­ty cov­ered us­es or pe­riph­er­al fea­tures of the drug, such as its man­u­fac­tur­ing process­es or de­liv­ery de­vices. The me­di­an time of patent fil­ing was more than a decade af­ter ap­proval of the orig­i­na­tor bi­o­log­ic, and one-fifth of the patents had no equiv­a­lents — ei­ther patents or patent ap­pli­ca­tions — in the Eu­ro­pean Union, Cana­da or Japan,” re­searchers at Har­vard Med­ical School and the Cum­ming School of Med­i­cine at the Uni­ver­si­ty of Cal­gary wrote in a new Na­ture Biotech­nol­o­gy in­ves­ti­ga­tion.

While not­ing that sec­ondary patents filed a me­di­an of more than a decade af­ter a bi­o­log­ic’s ap­proval “were pre­dom­i­nant­ly in­volved in the lit­i­ga­tion af­fect­ing the mar­ket en­try of biosim­i­lars for nine key bi­o­log­ic drugs,” they al­so said their find­ings un­der­score con­cerns about the weak­ness­es of the US patent sys­tem, adding:

Al­though patent­ing stan­dards are sim­i­lar across ju­ris­dic­tions, their ap­pli­ca­tion by US patent ex­am­in­ers can be less strin­gent, a trend that has been at­trib­uted to sub­op­ti­mal re­source al­lo­ca­tion among oth­er rea­sons. For ex­am­ple, three ex­am­in­ers eval­u­ate a patent ap­pli­ca­tion in the Eu­ro­pean Union com­pared to one in the Unit­ed States. Patent ex­am­in­ers in the Unit­ed States al­so process more than dou­ble the num­ber of patents or claims an­nu­al­ly than Eu­ro­pean Patent Of­fice ex­am­in­ers. While our study found that many sec­ondary patents are at is­sue in biosim­i­lar ef­forts to en­ter the US mar­ket, an­oth­er study found the main hur­dle to mar­ket en­try of biosim­i­lars for 9 top-sell­ing mon­o­clon­al an­ti­bod­ies in Eu­rope was the key patent on the orig­i­na­tor prod­uct, not sec­ondary patents.

But some who track the biosim­i­lar in­dus­try close­ly don’t have near­ly as omi­nous of an out­look as oth­ers, some of whom think biosim­i­lars should just be scrapped for bi­o­log­ic price con­trols af­ter a cer­tain cut-off date.

Ron­ny Gal

Bern­stein an­a­lyst Ron­ny Gal said in a note last sum­mer that while the US mar­ket has been stag­nant re­cent­ly, he pre­dict­ed it will re­turn to growth as new mol­e­cules launch, with biosim­i­lars to Lu­cen­tis and Hu­mi­ra com­ing in the next 12 months.

“If this sounds to some of you like the gener­ic mar­ket cir­ca 2005, we tend to agree,” he wrote. “Fur­ther, we sus­pect this was not lost on some of some of the ear­ly win­ners in the biosim­i­lar mar­ket. They seem to be be­gin­ning to pur­sue next-stage strate­gies, e.g. No­var­tis go­ing to mid-size biosim­i­lars, Co­herus en­try to fol­low-on PD1, Pfiz­er and Am­gen launch­ing late-en­trant biosim­i­lars at prices above the mar­ket. There is an­oth­er decade of growth here (the gener­ics peaked in 2015) but the days of just de­vel­op­ing the largest five drugs and be­ing suc­cess­ful be­cause com­peti­tors made mis­takes are prob­a­bly reach­ing their end.”

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

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In­cyte hit by CRL on ex­tend­ed-re­lease JAK tablets, mud­dy­ing plans for Jakafi fran­chise ex­pan­sion

The FDA has rejected Incyte’s extended-release formulation of ruxolitinib tablets, in a surprise setback for the company’s plans to build on its blockbuster Jakafi franchise.

The ruxolitinib XR tablets are designed to be taken once a day, whereas Jakafi is indicated for twice daily dosage (although some patients can take it once daily).

According to Incyte, the FDA acknowledged in its complete response letter that the study submitted in the NDA “met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval.”

Zhi Hong, Brii Biosciences CEO

Brii Bio­sciences stops man­u­fac­tur­ing Covid-19 an­ti­body com­bo, plans to with­draw EUA re­quest

Brii Biosciences said it will stop manufacturing its Covid-19 antibody combination, sold in China, and is working to withdraw its emergency use authorization request in the US, which it started in October 2021.

The Beijing and North Carolina biotech commercially launched the treatment in China last July but is now axing the work and reverting resources to other “high-priority programs,” per a Friday update. The focus now is namely hepatitis B viral infection, postpartum depression and major depressive disorders.

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FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Sergio Traversa, Relmada Therapeutics CEO

Rel­ma­da makes 'crit­i­cal changes' to PhI­II tri­al to try and save de­pres­sion drug

Relmada Therapeutics is making changes to its Phase III study of its lead drug for major depressive disorder, in an attempt to avoid problems with a prior trial that showed little difference between the drug and a placebo.

That failure in October wiped 80% from Relmada’s stock price, and was followed by another negative readout a few months later. In both cases, the company said that there had been trial sites that were associated with what it called surprising placebo effects that skewed the results compared with the drug, REL-1017.

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Paul Song, NKGen Biotech CEO

NK cell ther­a­py-fo­cused biotech eyes SPAC deal

A small, Santa Ana-based biotech created in 2017 is looking to enter a SPAC deal as it lays out plans to begin trials in its lead cell therapy candidates and bring on new executives.

Graf Acquisition Corp. IV and NKGen Biotech announced Thursday, with few other details, that the two companies signed a non-binding letter of intent to “pursue a business combination.” Graf Acquisition II and III withdrew their IPOs last year.

Peter Hecht, Cyclerion Therapeutics CEO

Hard pressed for cash, Cy­cle­ri­on looks for help fund­ing rare dis­ease drug

Cyclerion Therapeutics may have the design of a Phase IIb study ready to go, but it’s scrambling for a way to fund it.

The company said in a press release that it’s “actively evaluating the best combination of capital, capabilities, and transactions available to it to advance the development of zagociguat,” its lead candidate for a rare, genetic mitochondrial disease known as MELAS.

In a separate SEC filing, Cyclerion once again flagged “substantial doubt about (its) ability to continue as a going concern.” As of the end of 2022, it had cash and cash equivalents of only $13.4 million.

Eu­ro­pean Com­mis­sion de­lays pro­pos­al for ma­jor changes to phar­ma leg­is­la­tion

The European Commission has once again delayed the release of its proposal for an overhaul of the continent’s pharmaceutical legislation.

The release, previously anticipated on March 29, will occur “slightly later” than expected due to the “very busy College agendas of the last few weeks,” a Commission spokesperson told Endpoints News via email.

While the agency hasn’t provided an updated timeline, the spokesperson said the agenda is “always indicative and adoption dates of Commission proposals may change any time, especially when these proposals concern reforms of complex legislations of major importance.”