AstraZeneca’s Covid-19 vaccine woes, Moncef Slaoui resigns over sexual harassment claims, FDA acts tough, and more

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.

You know the week has been overflowing with news when stories that you thought were huge on Monday get largely buried by Wednesday and full news cycles get wrapped into one report. It may be a good idea to sit down for this edition — it’s going to take a while.

José Baselga’s shocking death and legacy

The sudden death at 61 of José Baselga, the brilliant oncology R&D chief at AstraZeneca and a towering figure in cancer drug development who had earlier been chief medical officer at Memorial Sloan Kettering, shook the industry before the week even began. The outpouring of tributes and farewells from colleagues and former collaborators reflected the breadth of his legacy. Baselga succumbed to Creutzfeldt-Jakob disease, a rapidly progressive and lethal but extremely rare neurodegenerative ailment. His daughter launched a fundraiser to support research into the condition, which you can see here.

AstraZeneca tries to put out fire

AstraZeneca confidently declared a 79% efficacy figure for its Covid-19 vaccine in a US trial, assuming it had a straight path toward an EUA. Little did it know it was steering straight into a storm, as the NIH issued a middle-of-the-night statement just hours later raising concerns about the data they chose to disclose. As it turned out, the Data and Safety Monitoring Board overseeing the trial blasted AstraZeneca for cherry-picking the most favorable number rather than more complete and recent results — an act that they said would erode public trust. The company tried to put out the fire with a primary cut of the more up-to-date numbers, suggesting the vaccine is 76% effective — although the fullest picture may not emerge until the FDA reviews the full dataset.

Moncef Slaoui accused of sexual harassment

Moncef Slaoui — whom GlaxoSmithKline terminated as the board chair at its bioelectronics joint venture Galvani following allegations of sexual harassment and inappropriate conduct from an employee that GSK said was “substantiated” in an investigation — has officially cut all professional ties with his resignation from the VC firm Medicxi. The longtime GSK exec had been immersing back into biopharma after wrapping a stint as the vaccine czar of Operation Warp Speed. Reprimanded by Emma Walmsley in a company-wide letter, Slaoui had offered an “unreserved” apology to the employee involved and stepped down from two biotech boards.

FDA takes Pfizer to task over tanezumab

The future isn’t looking bright for Pfizer and Eli Lilly’s anti-NGF osteoarthritis drug tanezumab. Following an in-depth review from the FDA that raised a litany of concerns about significant safety risks, an advisory committee voted almost unanimously to recommend against its approval. Per the regulators’ assessment, the 41 trials Pfizer has run over 15 years offered “substantial evidence of effectiveness” but the proposed risk evaluation and mitigation strategy may not be enough to assuage fears of joint-related problems. Outside experts agreed, with many asking for long-term followup studies and at least one going further to say the drug didn’t seem any better than aspirin or ibuprofen, or even placebo.

Biopharma’s diversity problem

Among the many issues that the Covid-19 pandemic has exposed is the troubling underrepresentation of minority groups in clinical trials. But how did the industry get here, and what are some ways to break those structural barriers to inclusion? Investing in communities, building trust and fostering diversity from the top down are going to be crucial, Nicole DeFeudis writes. And if Moderna’s move in its vaccine trial is any signal of what’s to come, the industry could be headed for a tipping point.

Can better labeling avert a disaster?

A consortium of pharma and tech companies is coming together to solve a seemingly esoteric but potentially deadly problem: how drugmakers actually keep track of where a patients’ cells are going. “We are begging for standardization wherever possible,” an expert told Kyle Blankenship, and labeling and identity of cells are one of the most important areas for that. Otherwise, “someone is going to make a major mistake, and we are racing against time,” said Amy DuRoss, whose company, Vineti, is offering an open source tracking system.


PREMIUM

Lonnie Moulder aims global 

You haven’t heard much from him, but Lonnie Moulder hasn’t been idle in the two years since he closed the $5 billion sale of Tesaro to GlaxoSmithKline. And he’s finally ready to take the limelight as interim CEO of Zenas BioPharma, a biotech startup with roots in China and the US for which he has assembled a pipeline with seven drugs. Europe will soon be added to the frame as he pursues global deals that will set him up to pursue all three of the world’s top pharma markets. This time, though, the cancer-oriented Moulder is jumping into new arenas, autoimmune conditions and rare diseases.

BridgeBio clears early hurdle with NIH help

Mike Collins, an NIH researcher and division chief who specializes in bone and mineral metabolism, gave BridgeBio’s Calcilytix team the idea to treat a rare genetic disease called ADH1 with a calcium sensing receptor (CaSR) antagonist. Two years later, the biotech — with the help of a principal investigator from the NIHhas laid out a clear set of data from a tiny, 6-person Phase II study showing how the drug they selected did exactly what they wanted it to: raising the level of calcium in the blood to normal levels while whittling back the overabundance of calcium in urine. The bigger test, though, is still ahead.


PEOPLE

  • Longtime Gilead R&D chief William Lee is hanging up his cleats, and Dan O’Day has recruited Flavius Martin from Amgen to run the game. Martin, who led Amgen’s research for the oncology, inflammation and cardiometabolic units out of South San Francisco, is expected the carry the torch in immuno-oncology.
  • Diana Brainard, one of the masterminds behind Gilead’s Covid-19 drug remdesivir, is jumping ship to take up the CEO post at antiviral T cell player AlloVir. She takes over from David Hallal, who has recruited the biotech to his manufacturing basecamp.
  • In the latest refresh for Merck’s C-suite, Caroline Litchfield is getting promoted to CFO, replacing Robert Davis as he moves to the top job vacated by Ken Frazier. The current treasurer, Litchfield is a veteran at the company for more than three decades.
  • Giovanni Caforio had a relatively tame year compared to the other Big Pharma CEOs throwing themselves into the Covid-19 fight, but he’s still rewarded with a $20 million pay package for overseeing the big Celgene integration and confronting a parallel crisis in health disparities.

FDA+

  • Amy Abernethy, the FDA’s principal deputy commissioner of food and drugs and acting chief information officer, is making a surprise exit from the agency after a little more than two years — during which she spearheaded a major restructuring of IT and established standards for real world evidence. Her departure couldn’t come at a more critical time.
  • Should the industry brace itself for a tougher regulatory environment? SVB Leerink analyst Geoffrey Porges sparked a debate with new predictions about restrictions on drug pricing, challenging FDA drug reviews and greater scrutiny of M&A. And while some FDA watchers are wary of calling it a shift so soon, a Senate committee has kicked off talks on drug pricing reforms with a Republican calling the current system “a mess across the board.”
  • The FDA needs to be having better and clearer scientific dialogues to foster the development of complex generics, Teva COO Christine Baeder argued in an interview with Zach Brennan, as the spotlight shines on the next iteration of the Generic Drug User Fee Amendments.
  • The HHS inspector general has cleared a Novartis program that pays for low-income patients to access its $475,000 CAR-T therapy Kymriah, praising its effectiveness while ruling the risk of overutilization is low.

R&D

  • In a first for the LAG-3 class, Bristol Myers Squibb says a combination of relatlimab and its PD-1 Opdivo significantly extended progression-free survival in a Phase III study for melanoma. It’s a big win for both Bristol and the so-far laggard pathway, which has drawn a pack of pharma and biotech players.
  • Roche’s R&D team was handed a mixed bag this week. On one hand, it staked a toehold in the $12 billion race to push checkpoint therapies into earlier stages of cancer, as Phase III data suggested adjuvant use of its PD-1 blocker Tecentriq helped early-stage lung cancer patients live longer than chemotherapy did. On the other, the pharma giant has halted dosing for its late-stage study of tominersen, an antisense drug it licensed from Ionis in hopes of tackling Huntington’s disease.
  • A failed Phase IIa study left little to salvage for Frequency Therapeutics’ four-shot treatment regimen for hearing loss. But the execs, who insist the trial design is to blame, still sees a way forward with a single dose.
  • Novartis says a $2 billion drug in its radiopharmaceuticals portfolio has delivered “groundbreaking” data for prostate cancer, hitting both co-primary endpoints on overall survival and radiographic progression-free survival while setting them up for a potential blockbuster future.

DISCOVERY

  • A pair of veterans of George Church’s lab tracked the poop of 200 wild animals over the last four years. Now, they say they’ve gathered a vast trove of genetic information that could be mined for new drugs on a long list of diseases — with backing from an Israeli billionaire.
  • Can a “super-seasonal” flu shot offering protection for three to five years bridge the gap between current and universal vaccines? The NIH and the University of Washington are taking a shot into the clinic this April after publishing animal data suggesting broad response to their nanoparticle technology.

REGULATORY

  • Novo Nordisk has been slammed with a refuse-to-file letter from the FDA regarding a once-weekly semaglutide injection at the 2 mg dose level, a rare rebuke for the Danish diabetes drug maker’s most high-profile program.
  • Safety signals observed in a postmarketing study have spurred the FDA to add a new warning to the label of GlaxoSmithKline’s shingles vaccine Shingrix, noting it was associated with an increased risk of a rare but debilitating disorder known as Guillain-Barré syndrome.
  • About two and a half years after selling off royalties on a disappointing Sanofi-partnered diabetes drug, Zealand Pharma has a new in-house product to boast about. The injectable dasiglucagon will be sold as Zegalogue to treat severe hypoglycemia.
  • Merck may be on the firing line for accelerated approvals of Keytruda, but that hasn’t stopped it from adding a new approval for the PD-1 inhibitor as a combination therapy with chemo to treat frontline metastatic esophageal cancer or gastroesophageal junction carcinoma.

CORONAVIRUS

  • The US will no longer distribute Eli Lilly’s bamlanivimab alone due to the increasing spread of coronavirus variants, although hospitals can still order the antibody as part of a combo. The countrywide halt follows the government’s decision to stop delivering the monotherapy to three states where variants ran rampant.
  • GlaxoSmithKline and Vir are submitting their monoclonal antibody, VIR-7831, for an emergency use authorization in mild-to-moderate Covid-19 patients, pursuing a similar indication as currently authorized antibodies based on recently announced Phase III data.
  • Albert Bourla declared that Pfizer is ready to go solo, if necessary, on future mRNA endeavors, having accrued decades worth of experience over the past year working with BioNTech on the ultra-fast development of a Covid-19 vaccine. The current pipeline, though, still appears to lean heavy on the German partner.
  • Regeneron says it will seek an EUA for a lower dose of its antibody cocktail, which was shown to reduce hospitalization or death by 70% in a new Phase III study. The 1,200 mg dose appeared just as good as the authorized 2,400 mg dose, with some evidence indicating that even smaller doses, as low as 300 mg, might already be enough.

STARTUP

  • A group behind the technology leading to J&J’s Covid-19 vaccine has scored some $47 million to test out a new kind of preventative product: a nasal spray that can protect people from broad virus families temporarily. It’s early days, but a look under the hood was evidently enough to get GV, F-Prime and some seasoned antiviral experts excited.
  • RA Capital’s low-profile small molecule incubator has spawned a neuro upstart, with $80 million to go after hyperexcitability disorders from chronic pain to epilepsy to depression. “It’s a lot about execution,” CEO Bob Azelby said, which is where the experienced C-suite comes in.
  • Microsoft and Sam Altman are backing a self-professed AI enthusiast’s take at a computational drug discovery platform, with ambitions spanning ophthalmology, infectious disease, neurology, immunology and aging.

PHARMA

  • Novartis’ top ranks are eager to separate the company from its troubled past — but legal records are keeping them grounded. In an unusual statement, the Swiss drugmaker pushed back on comments from chairman Joerg Reinhardt claiming they never bribed doctors, calling it “inaccurate and inconsistent” with what they admitted in court.
  • Thanks to a $150 million endowment from Eric and Wendy Schmidt, the Broad Institute is opening a new center to explore what director Todd Golub calls the dual revolutions of biology and machine learning. A few pharma partners have already gathered at its wings.
  • AbbVie is on the offensive over Humira two years before the first biosimilars to the megablockbuster are expected to hit the market, taking one Icelandic developer to court over allegations it stole trade secrets to create its copycat version.
  • Continuing its fight against a Trump-era rule to allow drug imports from Canada, industry group PhRMA has now petitioned the FDA to reject New Mexico’s import plan because of missing details that may make the imported drugs unsafe and not cost-effective.

FINANCING

  • Biotech VC bets continue to run the gamut as Gyroscope grabbed $148 million on the heels of positive data on its dry AMD gene therapy, Brii capped a tumultuous month with $155 million in fresh funding for an infectious disease pipeline, while the protein printing shop AbSci closed a $125 million crossover round. Other venture ideas reloading in cash this week revolve around bispecifics, eye cancer, IL-2s, CTPS1 and gene therapies for coronary heart disease.
  • The eruption of biotech IPOs propelled Lava Therapeutics and its gamma delta T cell-targeting bispecifics to a $100.5 million raise to start the week. Edgewise and Design Therapeutics, Ikena Oncology and Universe Pharmaceuticals followed, grabbing a collective $566 million for drugs targeting rare muscle ailments, degenerative disorders, metabolic pathways and the elderly.
  • Things were quieter on the filing side, though both of the new S-1s are notable: Recursion is looking to take its AI platform public after a hefty Series D, while Zymergen would pave the way for synthetic biology companies to debut on Nasdaq. Chardan brought the latest SPAC deal, pulling Renovacor onto Wall Street to advance an AAV‑based gene therapy that would fix a rare heart mutation.
  • With an eye on early-stage biotech, RiverVest Venture Partners has closed its largest fund yet at $275 million. The goal would be to “participate more fully” in later rounds and double down on its quick exit strategy.

MANUFACTURING

  • To rise up to the challenge of mass-producing mRNA vaccines — at a cost and scale previously unthought of — the head of design at Ginkgo Bioworks drew inspiration from the project he was working on before the pandemic: making synthetic meat.
  • With sales of Zolgensma flagging, Novartis is shuttering the Longmont, CO manufacturing plant it leased from AstraZeneca just a year ago. The departure leaves 400 employees without jobs, as the pharma giant concentrates production of current and future gene therapies in two other sites and contract networks.
  • Set out to be a central player in the cell therapy 2.0 movement, Lyell is preparing to open a $65 million manufacturing center in the Seattle area — one designed in a way that they “wouldn’t be fitting a square peg into a round hole in the future.”

DON’T MISS

  • More than two years after emerging from stealth, Maze Therapeutics has opened up its $191 million pipeline for a first look. The pipeline features three programs, including a new small molecule approach for the rare lysosomal disorder Pompe disease, a chronic kidney disease target that will put them in square competition with Vertex, and an ALS gene therapy that theoretically could be marketed for the entire patient population.
  • 2021 was supposed to be the year Odonate filed an NDA for its metastatic breast cancer drug. Instead, the biotech is scrapping those plans and winding down operations in one fell sweep after determining the data package is unlikely to support approval of its oral chemo. At last count, 153 staffers were on board.
  • Looking to replicate Roche’s success with Evrysdi, Takeda has racked up another early-stage discovery deal with Evotec to develop RNA targets ripe for small molecule therapeutics. The pact builds on other collaborations with the German player.
  • UK software provider Insightful Science is acquiring Dotmatics, a cloud-based scientific R&D data management platform founded by two ex-Merck scientists and based in San Diego, to beef up its cloud research platform.

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