Bristol Myers Squibb scores TYK2 OK; ARCH backs mRNA platform play; Illumina’s $8B conundrum; Sizing up Alnylam's win; and more

10 Sep 2022
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Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.
Trying to keep up with all the news coming out of ESMO? Well, other than the special event section below, we’ll also be updating the website throughout the weekend. If you prefer a summary, join Arsalan Arif and John Carroll for a virtual recap and analysis on Monday, when we will also publish a special report.
Bristol Myers Squibb scores TYK2 OK
Bristol Myers Squibb made a megablockbuster bet on deucravacitinib, the experimental TYK2 drug the company landed in the Celgene buyout, keeping it while auctioning off the rival Otezla to Amgen for $13.4 billion. Friday evening, that bet paid off in a landmark win, with Bristol Myers getting a green light to sell the first-in-class oral psoriasis drug — as Sotyktu (get it?) — for $75,000 a year as analysts project peak sales in the $3 billion-plus range. And there’s a big bonus.
ARCH backs mRNA platform play
John Maraganore — who led the charge of pioneering RNA interference at Alnylam — is co-founding a new platform company to explore everything else in the RNA field. There’s no number on how much Orbital will raise yet, but ARCH, a16z and Newpath Partners are clearly ready to bet however big they need. Beam is helping seed the startup with a suite of linear RNA and lipid nanoparticle knowhow, which will be combined with several new technologies from Orbital’s star scientific co-founders. Beam president/CSO Giuseppe Ciaramella, an early Moderna employee, is the interim CEO.
Illumina’s $8B conundrum
In a whiplash blow to the sequencing giant, European regulators blocked Illumina’s $8 billion acquisition of Grail just days after it prevailed over an FTC challenge. The EC said the deal would have stifled innovation and granted Illumina an unfair advantage over rivals in the blood-based cancer screening market. And as Jared Whitlock writes, that leaves Illumina with few good options moving forward — with divestiture seeming most likely.
Sizing up Alnylam’s win
Amid much anticipation, Alnylam detailed positive APOLLO-B data for its pivotal trial of patisiran in treating transthyretin-mediated — or ATTR — amyloidosistransthyretin-mediated — or ATTR — amyloidosis with cardiomyopathy. And the results spell out a clear advantage over a placebo in preventing a rapid decline in a 6-minute walk test. But bound to get immediate attention are unanswered questions on the drug’s health benefits and how the drug and placebo data tracked in the study for an increasingly common heart ailment compared to the disaster that befell a rival therapy at BridgeBio.
Two preclinical deals for Roche
Roche is on the hunt for something new. In search of first-in-class projects, it tapped PhoreMost, a small biotech working out of Cambridge, UK, for a target discovery pact in which PhoreMost will deploy its screening platform — which searches for the right pockets in target proteins to bind with — toward certain pathways in hematology and immunology selected by Roche. Days later, it bought out Good Therapeutics and its PD-1 modulated IL-2 program for $250 million in upfront cash, plus milestones. The rest of Good will be spun into a new company called Bonum.
Adcomm thumbs up for Amylyx
Second time’s the charm for Amylyx and its experimental ALS drug. In an unusual twist, outside experts on an FDA advisory committee voted 7-2 in favor of approving AMX0035, just months after voting against the drug in a first adcomm. Even more unusual was a promise from both CDER’s neuroscience director Billy Dunn and Amylyx’s co-CEOs that AMX0035 would be pulled from the market if the drug fails its ongoing Phase III PHOENIX trial.
Where did funny go?
What happened to humor in pharma advertising? That’s the question Endpoints MarketingRx editor Beth Bulik decided to delve into for her weekly feature. While survey results suggest people still want brands and marketing to be funny, business leaders overwhelmingly say they are afraid of using humor in messages to customers. She talks to experts about how they strike the balance and find the right place, right time, right people to be funny with.
#ESMO22
Ever since Roche nabbed a landmark approval for its PD-L1 Tecentriq in liver cancer In 2020, a number of drugmakers have tested their checkpoint inhibitors for the same indication. Three of them — Merck and Eisai with a Keytruda/Lenvima combo, Jiangsu Hengrui and Elevar with a camrelizumab/rivoceranib pairing and BeiGene with tislelizumab alone — spelled out their findings. And they’re all different.
Relay Therapeutics had steadily raised the bar for RLY-4008, its bile duct cancer drug for a narrow group of patients with FGFR2-altered cholangiocarcinomaFGFR2-altered cholangiocarcinoma. And now it’s arriving in Paris with an improved performance that appears to pave a direct path to a quick approval. The ORR, as an analyst observes, is more than double that of the pan-FGFR inhibitors now in use.
This weekend at ESMO, the KRAS battle between Amgen and its pesky biotech rivals at Mirati will continue with new slices of combo data for advanced cases of colorectal cancer. And once again, Mirati will get in with a solid punch. Both of them have updated data on their KRAS drugs in combination with an EGFR inhibitorEGFR inhibitor.
The long-awaited OS data for Gilead’s Trodelvy are finally in — the results that were touted as “clinically meaningful” for a subset of metastatic breast cancer patients. And at a median OS of 14.4 months versus 11.2 months for chemotherapy, the results were a bit better than analysts had predicted.
A little more than four years after Bristol Myers Squibb proudly unveiled a $3.6 billion, next-gen I/O alliance with Nektar, investigators turned up at ESMO with the full set of disastrous data that helped ice the whole deal. Not only did Opdivo plus NektarNektar’s IL-2 therapy bempeg flunk a Phase III melanoma study, the combo actually performed significantly worse than Opdivo alone.
Long-term data on AstraZeneca and Merck’s blockbuster cancer drug and European confab staple Lynparza were a mixed bag. While the drug ushered in the PARP inhibitorPARP inhibitor market in 2014, five-year follow-up results in the first-line advanced ovarian cancer setting missed statistical significance on OS, even though the absolute numbers are still good.
A few months ago, while rumors were swirling about a potential Merck buyout, Seagen posted a topline look at its Padcev–Keytruda combo as a first-line therapy for advanced bladder cancer. An ESMO abstract filled in some of the gaps in the data and offered a look at durability, although some important metrics remain unanswered.
On the cusp of asking the FDA to approve its cancer drug for progressing desmoid tumors, SpringWorks is out with a fuller picture of the therapy’s performance in a Phase III trial four months after declaring a topline win. But ahead of its scheduled presentation, it also teed up a $225 million private placement and an expanded pact with GSK on a Blenrep combination.
Merck came into ESMO confident that it reigned supreme in the adjuvant setting for renal cell carcinoma — the new frontier for checkpoint inhibitors. Data from Roche and Bristol Myers Squibb only serve to highlight Merck’s dominance, as it spelled out the latest, improved hazard ratio for King Keytruda, cutting risks on disease-free survival by 37%.
Bristol Myers Squibb’s dual Opdivo/Yervoy immunotherapy strategy is seeing mixed data in kidney cancer. While Bristol Myers’ own Phase III study failed the primary endpoint of disease-free survival, Exelixis is showcasing Phase III data where a combination of Cabometyx with Opdivo and Yervoy improved PFS over the PD-1/CTLA-4 combo alone. But toxicities may cast a shadow over their use.
No stranger to big conference presentations, Merck’s heavyweight Keytruda is back with a hit and a miss. The first, testing the drug in the neoadjuvant or adjuvant setting for melanoma, delivered positive event-free survival data. The other, focused on head and neck cancer, failed to hit statistical significance despite what the company calls a favorable trend.
Eager to prove its cell therapy, Adaptimmune presented the newest Phase I SURPASS trial data for its MAGE-A4 program. Among 44 patients who received a single dose of the therapy (all evaluable except for one), investigators tracked a 44% ORR. But two deaths were also recorded as related to the treatment.
AstraZeneca spinout Dizal said its cancer drug cleared the primary goal in a Phase II trial of lung cancer patients in China with EGFR exon 20 insertion mutations. Touting an ORR of 59.8%, Dizal will be going against Takeda and J&J, both of which have approved meds for this subgroup, as well as others like Cullinan Oncology and Blueprint Medicines.
There’s a plethora of protein degradation biotechs, and a smaller handful of protein stabilization players, but Lizzie Ngo was searching for something more. The principal at Longwood Fund landed on an idea surrounding the activation, inactivation and trafficking of proteins by coopting phosphorylation. Photys Therapeutics is launching with a $75 million initial haul.
Unlike in other neurodegenerative diseases, such as Alzheimer’s, the pathology of Parkinson’s is relatively well-understood. But the knowledge has yet to translate into newer, more effective therapies. Innervace, a new biotech launched out of Penn and backed by Deerfield, wants to change that with a procedure called deep brain stimulation. The Series A comes in at $40 million.
With a sharp eye on transcription — the process of creating RNA from DNA — Colorado-based Arpeggio Biosciences raised $17 million in a Series A round, two years after a $3.2 million seed round and four years after creation. While transcription factors are hard to drug directly, the biotech hopes to design and screen molecules that can alter the transcripts.
FINANCING
If ArsenalBio does it right, its first CAR-T candidate — a potential treatment for ovarian cancer — will be in the clinic later this year. And a group of deep-pocketed investors is handing over $220 million to push it along. The planned trial will mark a big test for ArsenalBio’s suite of technologies, which promise to overcome the barriers keeping CAR-T from solid tumors.
Joel Dudley’s first investment since joining former Google CEO Eric Schmidt’s firm is an $8 million seed round for Harmonic Discovery, which is building a platform to design small molecule drugs that can target multiple proteins at the same time, with a special focus on kinases and an eye to utilizing machine learning to help with the process.
It’s time to turn off the lights at Metacrine. The party ended months ago for the Rich Heyman startup, which came out of the IPO gate in 2020 with high hopes of pursuing a drug for NASH. It’s being bought out by another struggling biotech, Equillium, which made it clear that it was primarily interested in Metacrine’s cash balance and doesn’t plan on retaining the employees.
After whittling itself down from 41 to just six employees following a fruitless readout on its blood disorder drug earlier this year, Imara found a buyer to exchange the drug for cash. Imara will be selling its sickle cell disease and beta thalassemia drug to Cardurion Pharmaceuticals, a cardio upstart that got $300 million from Bain last year. The deal is for $35 million upfront, with some biobucks attached.
In March, Zealand Pharma gutted its US workforce and said it was looking for strategic partnerships for its diabetes products following a disappointing first year on the market for its diabetes treatment Zegalogue. It found the partner in Novo Nordisk, which is paying about $3.3 million upfront to take over worldwide marketing.
Having scored their first FDA approval, the dermatology specialists at Arcutis pounced on a new buyout to beef up the pipeline. They are acquiring Ducentis BioTherapeutics in a hybrid deal comprising $16 million in cash and roughly $14 million in stock, mainly to get their hands on a preclinical checkpoint agonist that they believe can work well with their lead drug.
Basilea Pharmaceutica is one more step closer to its final days as an oncology company. As part of its pivot to anti-infectives, the Swiss company sold its preclinical PARG checkpoint inhibitor program to UK-based Nodus Oncology in exchange for upfront and near-term research milestone payments of just over $1 million, plus milestones.
As the CRO industry continues to consolidate, another company is looking to get in on the multinational action with its latest move. Avance Clinical, an Australian-based CRO, acquired US-based research organization C3 Research Associates, giving the company a solid foothold on North American soil. The private equity group Riverside backed Avance’s move.
CORONAVIRUS
Less than a week after the FDA signed off on Omicron-specific bivalent Covid vaccines from both Moderna and Pfizer, federal health officials announced that the shots will be available to most Americans by the end of the week as shipping of doses has begun nationwide. They believe that could prevent up to 100,000 hospitalizations this fall and winter.
As Moderna pivots away from Covid-19 to other vaccines, the mRNA-focused biotech is still plotting how it could hit $13 billion in annual US Covid-19 vaccineCovid-19 vaccine sales, with $100 shots and 50% of all adults getting a booster. The company noted it will move to value-based pricing as it moves from the pandemic setting to the commercial market.
Searching for ways to treat long Covid, a new collaboration — bringing together researchers from leading institutes in academia — will hone in on what the virus does to “drive chronic disease,” research how SARS-CoV-2 affects the immune system and what effects it could have on cognitive function, nerve signaling and other processes. Two billionaires are backing the project with $15 million to start things off.
The FDA is now following through on an emergency use filing for a repurposed cancer drug that European regulators initially took an interest in. The agency will convene an adcomm to discuss Veru’s EUA — specifically, combing over the treatment effect size given “the high placebo mortality rate, the limited size of the safety database, and identifying the proposed population.”
R&D
After a scandal involving doctored images, a very public board fight and a Phase II fail took the wind out of its sails, Athira plotted a comeback for its unconventional approach to treating Alzheimer’s. In amending the failed Phase II trial to include new measurements — and shining a spotlight on a biomarker called neurofilament — it also hints at a possible accelerated approval pitch.
Moderna CEO Stéphane Bancel’s vision to become a 40-drug company is materializing at a time analysts say the urgency is increasing for it to deliver on programs outside of Covid-19. Going through its mRNA pipeline for the annual R&D day, the biotech spotlighted some early data for orphan drug programs while previewing key vaccine readouts.
It’s challenging enough to get one cancer drug approved. But it looks like Erasca is gunning for its two lead candidates in combination — though both are still in very early stages. Pooling the analysis of its two ongoing trials — one for an ERK1/2 inhibitorERK1/2 inhibitor and the other for an SHP2 inhibitorSHP2 inhibitor — the company says it will begin dose escalation for the combo soon.
Less than two months after expanding its immuno-oncology partnership with Roche’s Genentech, Bicycle Therapeutics touted some new in-house data on its lead program. While execs viewed the data as positive, with a handful of responses among a dozen very sick patients, analysts were
Several years after securing $100 million cash to pursue its lead drug in certain allergic and inflammatory diseases, one-time high flier Allakos is now pivoting its R&D efforts to other diseases and another potential candidate. The Phase III study tested its lead drug in confirmed eosinophilic duodenitis, and it met one co-primary endpoint but missed the other.
Eye-focused biotech Iveric Bio reported positive Phase III results for its injectable complement C5 protein inhibitorcomplement C5 protein inhibitor, saying it met the primary endpoint of the mean rate of growth in geographic atrophy over 12 months. Building on its first Phase III win, the readout paves the way for an NDA filing by the end of Q1 next year.
Pacira Biosciences is hoping that the latest data surrounding its non-opioid painkiller will expand its usage post-surgery. Presenting topline results from a Phase III study investigating its bupivacaine-based treatment Exparel for post-surgical use in patients undergoing a total knee replacement, the company reported that the drug hit the primary endpoint in pain scores compared with a different formulation.
The FDA approved AstraZeneca’s PD-L1 Imfinzi in combo with gemcitabine and cisplatin for advanced biliary tract cancer, making it the first immunotherapy for this patient group. The combo was shown to improve overall survival in a Phase III trial, surprising many as both Keytruda and Opdivo failed in this setting.
Revance Therapeutics finally landed an FDA approval for its Botox competitor, known as Daxxify final, after initially submitting the original BLA way back in January 2020. The botulinum toxin products will compete to temporarily improve moderate to severe frown lines — what Revance estimates is a $3.2 billion and growing market. The hope is that its longer-lasting property will make a difference.
In an effort to push a high-dose version of Eylea, Regeneron unveiled a pair of trial wins, securing a way to unlock a likely extension to its multibillion-dollar franchise. The higher dose lends itself to longer dosing regimens, and both trials hit noninferiority in vision gains for patients with diabetic macular edema and wet age-related macular degeneration.
It’s time to review and revise federal guidance on pharma manufacturers’ donations to patient assistant charities, according to a new study that takes a deep look into drugmakers’ incentives by calculating patients’ cost sharing and manufacturers’ revenues. The authors conclude that the leading companies would find it profitable to donate, which violates the spirit of anti-kickback statutes.
While just three brand-name inhalers approved between 1986 and 2020 now face generic competition, the same sort of long monopoly extensions are not as prevalent for nebulizers, a new study published in Nature Biotechnology explains. To address the ways developers obtain a longer period of exclusivity, the author pointed to regulatory reforms.
Ofev was one of Boehringer Ingelheim’s top sellers in the first half of this year, raking in a whopping $1.48 billion. Now the German pharma giant wants to expand into the small group of pediatric patients with lung scarring diseases, with Phase III results in hand suggesting its dosing regimen works in kids.
LAW
J&J has settled a case with a former employee who accused top execs — including former CEO Alex Gorsky and former R&D head Matthai Mammen — of gender discrimination and retaliation leading up to her eventual termination after 25 years with the pharma giant. The case was dismissed with prejudice on Aug. 8, after the dispute had been “amicably resolved,” according to court documents released a week ago.
While the SPAC market continues to oscillate between inked deals, nixed agreements and pulled IPOs, Perceptive Advisors will have to pony up $1.5 million to the SEC for what the regulator deemed “conflicts of interest” related to blank check dealings. Perceptive, which founded multiple SPACs, was charged for failing to disclose its ownership of sponsors of SPACs into which it advised clients to invest. The firm said it’s cooperating with the SEC.
Once riding high with a market value close to $1 billion, Geron settled an investor lawsuit for $24 million. Stockholders claimed the company wrongly touted early data for a Janssen-partnered cancer drug candidate and failed to reveal the actual disappointing primary endpoint results, something they realized after reading news reports from STAT’s Adam Feuerstein.
Teva fired back at GSK after the UK-based drugmaker sought to squash Teva’s attempt to get its “skinny” label case overturned by the US Supreme Court. In a reply, Teva slammed GSK’s claims around these label carve-outs and noted that the previous ruling in GSK’s favor “is more than just a misapplication of settled precedent: it is an about-face.”
The former CEO of a South Florida-based contract drug manufacturer has been sentenced to more than three years in federal prison over repeatedly lying to the FDA and allowing contaminated products to be sent to children’s hospitals. Raidel Figueroa was charged as part of an investigation into an outbreak of infections linked to Burkholderia cepacia, or B. cepacia.
More than a decade after its first day in court, Bayer is finally settling two whistleblower cases. The German drugmaker agreed to pay a $40 million fine to resolve allegations that it downplayed the safety risks of a statin drug and paid kickbacks to doctors and hospitals to convince them to prescribe two of its other drugs.
MARKETINGRX
Pharma’s big swing to digital advertising is finally losing steam — but still growing at a double-digit pace. While the pace is slowing down compared to the pandemic rush, a new report predicts $15.8 billion in 2022 spending, a 14% increase year over year. Based on this trend, the industry would hit just shy of $20 billion by 2024.
Continuing its effort to address the racial disparity that’s particularly pronounced in dermatological conditions, Kyowa Kirin is re-boosting the “Look Deeper at CTCL” campaign during Lymphoma Awareness Month with social media and digital posts aimed at raising awareness in the Black community about the rare cancer.
Genentech and Novartis are once again partnering with a well-known comedian to raise awareness of chronic idiopathic urticaria, also known as chronic spontaneous urticaria. Vicki Lawrence, known for her work as a cast member on “The Carol Burnett Show,” has been speaking out about her condition as “the face of hives.” New digital and social posts are re-upping the work and spotlighting the condition again.
Physicians’ empathy for patients sometimes comes from personal experience. That’s the case in Sun Pharma’s new campaign with 10 dermatology healthcare providers who talk about their personal experiences with acne. Sun’s dermatology business includes several acne treatments, and the company hopes it may help patients better relate to their doctors.
Does your pharma brand speak Spanish? Not just translating advertising copy into the language, but authentically speaking to people with consideration of different Hispanic cultures? That’s what pharma brands should be doing if they want to reach the “crucial” Hispanic audience, according to Publicis Health Media.
Pfizer is amping its science push this month with a round of new Facebook ads featuring bolder-than-norms pop culture takes; Bristol Myers Squibb and Jazz funded three new Stand Up To Cancer research teams for lung cancer and Ewing sarcoma; The American Lung Association teams with Sanofi to remind people, especially those with chronic medical conditions; to get their flu shots — learn more in the MarketingRx roundup.
FDA+
As Florida Gov. Ron DeSantis publicly feuds with the FDA after accusing the federal agency of dragging its feet on approving the state’s drug import plan, Colorado is announcing its own drug importation partnership with a handful of companies, including a Canadian subsidiary, in an attempt to bring down drug prices.
The FDA’s monthslong trial hold on Sarepta Therapeutics’ next-gen Duchenne muscular dystrophy drug is out the door after the biotech and regulator hashed out a new global trial protocol to expand monitoring of urine biomarkers. The hold was first issued after a serious adverse event of low magnesium levels in one patient’s blood was observed.
Almost a dozen new Humira biosimilars will finally launch in the US next year, beginning with Amgen’s in January (almost four years behind Europe). But Alvotech, which developers one of the top follow-on contenders, with a higher concentration version and a potential interchangeable designation to boot, was slammed with a rejection due to manufacturing issues.
Neulasta, one of Amgen’s oldest drug franchises, has another biosimilar to contend with. German pharma Fresenius Kabi got its pegfilgrastim biosimilar approved by the FDA, and it will be marketed as Stimufend as a therapy for neutropenia.
In a push to bring in new drug development tools, the FDA officially kicked off a pilot program designed to expand its qualification of those out-of-scope drug development tools by selecting Integral Molecular’s Membrane Proteome Array as the first participant. The cell-based array is used to evaluate off-target protein binding.
Eight years after the last version of guidance on pediatric clinical pharmacology studies, the FDA released updated draft guidance focusing on how sponsors of new drugs and biologics can best identify the appropriate pediatric doses of their developing products, as well as how to use disease and exposure-response knowledge from prior studies to inform future pediatric development.
MANUFACTURING
The latest leg of Merck KGaA’s expansion drive will take place in mainland Europe. It’s looking to invest around $129 million into single-use assemblies as part of the production of Covid-19 vaccinesCovid-19 vaccines and other therapeutics at its site in Molsheim, France, while building what it is calling the Launch and Technology Center in the city of Darmstadt, Germany. The $159.3 million center will look to produce small molecule-based drugs for clinical trials and eventual production.
Cell therapy player Orca Bio will expand its manufacturing capabilities by constructing a new 100,000-square-foot commercial facility in Sacramento, CA. As it starts a Phase III trial, the biotech says it wants dedicated space for its late-stage pipeline in addition to an existing facility for early-stage work.
Two years into the implementation of a requirement for manufacturers to report data annually to the FDA, the agency hosted a webinar to clarify the guidance. Several manufacturers and consultants also explained some of the challenges faced in reporting and what could be done to make the process smoother in the future.
Pharma manufacturing in Virginia is getting a large boost from the US Department of Commerce, which is dishing out $52.9 million in grants to support new capabilities and training programs for essential generic medicines. The plan is for a local manufacturing cluster to eventually increase the domestic supply of APIs.
An FDA inspection found several issues including spore-related contamination and missing logbooks in the manufacturing area at a site in the city of Chuncheon, South Korea, according to a Form 483. The inspection took place at a factory for Hugel, a maker of botulinum toxin(s), dermal fillers and other aesthetic products.
Catalent is looking to expand its clinical supply facility in Singapore; Cambrex, a drug substance, drug product and analytical services provider, completed the first phase of its $30 million expansion in North Carolina; HHS awarded a $19.8 million monkeypox vaccine distribution contract to AmerisourceBergen; make sure you don’t miss a beat by checking out our roundup of small manufacturing news.
DON’T MISS
Health inequity in the US increasingly drew attention through the pandemic, with long-existing disparities exacerbated — and spurring financial support and promises of help from pharma companies. Now the Merck Foundation is taking a step further with a new $20 million fund to focus equity efforts specifically on cancer care.
Pharma companies and advocates condemned a federal judge’s ruling that a Texas business shouldn’t be required to cover HIV-prevention drugs under religious freedom law. According to them, thousands of patients could be affected. ViiV, which markets a suite of PrEP drugs, says it expects the final ruling to be appealed.
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