GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, Glax­o­SmithK­line’s Benlysta be­came the first bi­o­log­ic to win ap­proval for lu­pus pa­tients. Nine years on, the British drug­mak­er has un­veiled de­tailed pos­i­tive re­sults from a study test­ing the drug in lu­pus pa­tients with as­so­ci­at­ed kid­ney dis­ease — a post-mar­ket­ing re­quire­ment from the ini­tial FDA ap­proval.

Al Roy Lu­pus Al­liance Re­search

Lu­pus is a drug de­vel­op­er’s night­mare. In the last six decades, there has been just one FDA ap­proval (Benlysta), with the field re­sem­bling a grave­yard in re­cent years with a string of fail­ures in­clud­ing UCB and Bio­gen’s late-stage flop, as well as de­feats in Xen­cor and Sanofi’s pro­grams. One of the main rea­sons the suc­cess has elud­ed re­searchers is be­cause lu­pus, akin to can­cer, is not just one dis­ease — it re­al­ly is a dis­ease of many dis­eases, not­ed Al Roy, ex­ec­u­tive di­rec­tor of Lu­pus Clin­i­cal In­ves­ti­ga­tors Net­work, an ini­tia­tive of New York-based Lu­pus Re­search Al­liance that claims it is the world’s lead­ing pri­vate fun­der of lu­pus re­search, in an in­ter­view.

Un­der­stand­ing the dis­ease at the mol­e­c­u­lar lev­el will help re­searchers un­der­stand that cer­tain drugs will be ap­pro­pri­ate for cer­tain pa­tients, he said. “I think our in­abil­i­ty to sort of bet­ter seg­ment the pa­tients is a domi­no ef­fect for us not to bet­ter iden­ti­fy the drugs, and then test them in the right pop­u­la­tion…so right now it’s sort of a hodge­podge ap­proach, we sort of throw spaghet­ti at a wall, and hope that some­thing sticks.”

Giv­en lu­pus is an au­toim­mune dis­ease, im­mune cells such as B cells and T cells are im­pli­cat­ed in its man­i­fes­ta­tion, which is why some can­cer drugs such as Roche’s Gazy­va that share some of the same mech­a­nisms of ac­tion are be­ing test­ed for lu­pus.

Richard Fu­rie North­well Health

GSK’s Benlysta, which in­hibits the repli­ca­tion of B cells, was ini­tial­ly al­so be­ing pur­posed for use in a host of au­toim­mune dis­eases such as rheuma­toid arthri­tis, but the lu­pus da­ta emerged most com­pelling, sug­gest­ed Richard Fu­rie, chief of the di­vi­sion of rheuma­tol­ogy and pro­fes­sor at the Fe­in­stein In­sti­tutes at New York State’s largest health­care provider North­well Health, who has in­ves­ti­gat­ed the use of the drug for over two decades.

Fu­rie is al­so the lead in­ves­ti­ga­tor of BLISS-LN, the tri­al that tracked Benlysta’s im­pact on the rough­ly 60% of pa­tients with the sys­temic au­toim­mune dis­ease who de­vel­op lu­pus nephri­tis (of which 1 in 4 progress to end-stage re­nal dis­ease) for two years. In the 448 adult pa­tient-tri­al, the in­tra­venous for­mu­la­tion (one-hour IV in­fu­sion month­ly) of the drug plus stan­dard care was com­pared to stan­dard care alone. The topline re­sults were first dis­closed last De­cem­ber.

De­tailed da­ta, pre­sent­ed at a med­ical con­fer­ence on Thurs­day, showed that 43% of lu­pus nephri­tis pa­tients in the Benlysta arm achieved pri­ma­ry ef­fi­ca­cy re­nal re­sponse—a mea­sure of kid­ney func­tion de­fined by re­duc­tion in pro­tein in urine —com­pared with 32.3% of pa­tients in the con­trol arm at 104 weeks. A key sec­ondary goal, com­plete re­sponse rate was al­so sta­tis­ti­cal­ly sig­nif­i­cant­ly in fa­vor of the Benlysta arm at 30%, ver­sus 19.7% in the con­trol arm. Oth­er end­points, such as time to death or re­nal-re­lat­ed event, all point­ed to Benlysta’s su­pe­ri­or­i­ty.

For now, with stan­dard care on­ly about a third of pa­tients are get­ting com­plete re­spons­es and so its key to get that com­plete re­sponse rate up — and com­pa­nies have been try­ing to do that for some 20 odd years, but it’s been fail­ure af­ter fail­ure af­ter fail­ure, not­ed Fu­rie.

“So this is re­fresh­ing be­cause it works,” he said. “So 11 per­cent­age points was the ef­fect size. And when any­body would ask me what kind of ef­fect size would I like to see or what min­i­mum ef­fect size would I’d like to see? My an­swer was al­ways 10%. Con­sid­er­ing how many pa­tients I’ve sent on dial­y­sis and how many pa­tients have got­ten kid­ney trans­plants. I will take that bar­ring any safe­ty is­sues. And there re­al­ly were no safe­ty is­sues in this study.”

While the re­sults are en­cour­ag­ing, and Benlysta en­joys its mo­nop­oly in the lu­pus space for now rak­ing in £613 mil­lion in sales last year, ri­vals are stack­ing up, es­pe­cial­ly in lu­pus nephri­tis (LN). Com­peti­tors have al­so pub­lished their own Phase III da­ta, but with­out head-to-head tri­als, com­par­isons are tricky.

For in­stance, Au­rinia’s oral drug, vo­closporin, gen­er­at­ed pos­i­tive piv­otal da­ta last De­cem­ber. When added to stan­dard-of-care the drug, which is de­signed to in­hib­it an en­zyme that ac­ti­vates T-cells called cal­cineurin, in­duced re­nal re­sponse of 40.8%, while those on the con­trol arm ex­pe­ri­enced a rate of 22.5% at 52 weeks. Al­though a pre­vi­ous mid-stage study brought up safe­ty con­cerns with the drug, af­ter more deaths in the vo­closporin arm were record­ed, the Phase III tri­al put those fears to rest with rough­ly sim­i­lar rates of se­ri­ous ad­verse events across both arms.

“De­spite pro­vid­ing Benlysta treat­ment for twice as long as vo­closporin, and set­ting the bar for re­nal re­sponse sub­stan­tial­ly low­er, Benlysta still on­ly man­aged to bare­ly hit sta­tis­ti­cal sig­nif­i­cance. In light of these re­sults, we re­gard the ben­e­fit of Benlysta in LN to be mar­gin­al, at best, sim­i­lar to its ben­e­fit in sys­temic lu­pus ery­the­mato­sus (SLE),” HC Wain­wright an­a­lyst Ed Arce wrote in a De­cem­ber note.

Last No­vem­ber, Roche’s Gazvya al­so gen­er­at­ed pos­i­tive mid-stage da­ta when com­bined with stan­dard care in LN pa­tients. The drug — en­gi­neered to at­tach to CD20, a pro­tein found on cer­tain B-cells — met the main goal of in­duc­ing a sta­tis­ti­cal­ly su­pe­ri­or com­plete re­nal re­sponse of 40% at week 76, ver­sus 18% in pa­tients giv­en stan­dard treat­ment, Roche said.

A num­ber of oth­er au­toim­mune and can­cer drugs are al­so be­ing re­pur­posed for use in LN and in the larg­er lu­pus pa­tient pop­u­la­tion. But for Lu­pus Re­search Al­liance’s Roy, a sin­gle tar­get ap­proach will not gar­ner the type of im­pact that could trans­form the lives of pa­tients, but a bis­pe­cif­ic strat­e­gy that is be­ing test­ed in ear­li­er stage tri­als from com­pa­nies just might.

“I think a B cell or a T cell sort of drug mech­a­nism is too my­opic, and I think that’s been borne out in the tri­als. Even in Benlysta, the ef­fect size was very small. So I think one sort of ther­a­py ei­ther tar­get­ing a B or T cell pop­u­la­tion is not go­ing to be enough,” he said. “And un­for­tu­nate­ly, be­cause we have a lack of ap­proved drugs, com­bi­na­tion ther­a­pies aren’t re­al­ly some­thing that we can em­ploy in lu­pus as you can em­ploy in oth­er dis­eases, par­tic­u­lar­ly can­cer.”

So some com­pa­nies such as Bris­tol My­ers and Am­gen are try­ing to ad­dress the het­ero­gene­ity of the dis­ease with­out know­ing how we strat­i­fy pa­tients at a mol­e­c­u­lar lev­el, rec­og­niz­ing that monother­a­pies at­tack­ing a sin­gle path­way aren’t very ef­fec­tive, he not­ed. “So the next best bet is to re­al­ly look at de­vel­op­ing a com­bo ther­a­py by virtue of hav­ing mul­ti­ple mech­a­nisms.”

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance Chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

Pharma brands are trying to figure out new ways to better reach patients and doctors, but also measure results. (Credit: Shutterstock)

Do phar­ma TV and so­cial ads work? Phar­ma mar­ket­ing agen­cies adopt­ing new tech so­lu­tions to find out

It’s a timeworn advertising question — is my ad campaign working? In pharma, that can be an especially difficult question to answer in part because of privacy regulations, but also because the brands spend a lot of money on TV commercials where viewers can’t directly click on an ad.

Healthcare marketing services companies like Lasso and CMI Media Group are trying to change that with new measurement methods and partnerships that aim to get closer to patients’ and physicians’ actions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Corey McCann, Pear Therapeutics CEO

Pear Ther­a­peu­tics touts Q2 growth while scal­ing back full-year goals and chop­ping 9% of staff

Pear Therapeutics set some ambitious goals back in March, predicting a five-fold boost in revenue and a surge in new prescriptions for its digital therapeutics. Now the company is scaling back those estimates and chopping 9% of its workforce — an all-too-common occurrence in biotech lately.

CEO Corey McCann unveiled Pear’s Q2 numbers on Thursday, touting a 20% quarter-over-quarter revenue growth totaling $3.3 million. That’s more than double what the company made in Q2 2021, and McCann thinks the team could see a nearly four-fold jump in revenue this year, falling in the range of $14 million to $16 million.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Seagen interim CEO Roger Dansey and Daiichi Sankyo CEO Sunao Manabe

Paving the way for Mer­ck­'s buy­out, Seagen los­es ar­bi­tra­tion dis­pute with Dai­ichi over ADC tech

As Seagen awaits a final buyout offer from Merck that could be in the territory of $40 billion, Seagen revealed Friday afternoon that it lost an arbitration dispute with Daiichi Sankyo relating to the companies’ 2008 collaboration around the use of antibody-drug conjugate (ADC) technology.

But that loss likely won’t matter much when it comes to Merck’s deal.

After breaking off its pact with Daiichi in mid-2015, the two companies battled over “linker” tech — a chemical bridge between an ADC’s antibody component and the cytotoxic payload — that Seagen claims Daiichi would improve upon and implement in its current generation of ADCs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.