John Leonard, Intellia CEO

In­tel­li­a's CRISPR pro­gram that ed­its genes di­rect­ly in pa­tients shows dura­bil­i­ty in AT­TR amy­loi­do­sis

The first in vi­vo CRISPR/Cas9 gene edit­ing pro­gram has some new dura­bil­i­ty da­ta show­ing sus­tained re­duc­tion of a tox­ic pro­tein in AT­TR amy­loi­do­sis at all four dose lev­els in a small 15-pa­tient study.

In­tel­lia Ther­a­peu­tics pre­sent­ed the much-an­tic­i­pat­ed da­ta for its Re­gen­eron-col­lab­o­rat­ed NT­LA-2001 Fri­day morn­ing, adding to the ini­tial Phase I re­sults it first de­liv­ered al­most a year ago to the day.

The Cam­bridge, MA, biotech’s shares $NT­LA climbed near­ly 6% be­fore the open­ing bell Fri­day.

In­tel­lia is now in talks with the FDA and oth­er reg­u­la­tors about tri­al de­sign for a po­ten­tial piv­otal study, the Jen­nifer Doud­na-found­ed biotech said on an in­vestor call Fri­day morn­ing. The much-tracked sin­gle-dose pro­gram, which ed­its genes di­rect­ly in­side the body, is be­ing in­ves­ti­gat­ed for two dif­fer­ent man­i­fes­ta­tions of AT­TR amy­loi­do­sis — polyneu­ropa­thy, where pa­tients have pe­riph­er­al nerve dam­age, and car­diomy­opa­thy, where pa­tients’ heart mus­cles don’t work well.

All re­sults since last June have been in polyneu­ropa­thy, with Fri­day’s da­ta drop show­ing sus­tained dura­bil­i­ty in the rare con­di­tion in which tox­ic pro­tein ac­cu­mu­lates in a pa­tient’s or­gans.

Back in Feb­ru­ary, In­tel­lia had said that at the high­est dose lev­el (1.0mg/kg), six pa­tients had shown a 93% mean re­duc­tion in the tox­ic pro­tein. In the new da­ta, three of those pa­tients reached the nine-month fol­low-up point and main­tained that lev­el of TTR re­duc­tion.

The mean re­duc­tion for the three pa­tients at the sec­ond-high­est dose (0.7mg/kg) was 86%. For the longest-tracked group, dose lev­el two at 0.3mg/kg, the three pa­tients had a mean re­duc­tion of 89%.

Part II of the study, which is on­go­ing, is test­ing a dose of 80mg, the fixed-dose equiv­a­lent of the high­est dose group in Part I, the com­pa­ny said.

Headaches, in­fu­sion-re­lat­ed re­ac­tions, back pain, rash and nau­sea were the most fre­quent ad­verse events across all four dose lev­els, the biotech said. Eleven of the 15 pa­tients re­port­ed a max­i­mal ad­verse event of grade 1. The most se­ri­ous ad­verse event, which In­tel­lia said was “pos­si­bly re­lat­ed” to its treat­ment, was grade 3 vom­it­ing in a pa­tient with a med­ical his­to­ry of gas­tro­pare­sis.

“Based on the in­ter­im da­ta shared to­day, we be­lieve NT­LA-2001’s po­ten­tial to be a trans­for­ma­tion­al treat­ment for pa­tients with AT­TR amy­loi­do­sis is be­com­ing clear­er. The safe­ty, depth of serum TTR re­duc­tion and dura­bil­i­ty pro­file demon­strat­ed thus far high­lights its po­ten­tial for halt­ing and re­vers­ing the dis­ease af­ter a sin­gle dose,” said CEO and pres­i­dent John Leonard in a state­ment.

The com­pa­ny will com­plete en­roll­ment for both the polyneu­ropa­thy and car­diomy­opa­thy arms of the tri­al lat­er this year and will present the first car­diomy­opa­thy re­sults by year’s end, In­tel­lia said.

In­tel­lia is try­ing to leapfrog Al­ny­lam’s On­pat­tro and re­cent­ly ap­proved Amvut­tra, as well as Io­n­is’ Tegse­di. Those are all RNA-tar­get­ing drugs, but re­quire con­stant dos­ing com­pared to In­tel­lia’s one-time ther­a­py. On­pat­tro and Tegse­di have shown re­duced mu­tant pro­tein ex­pres­sion by about 80%.

Al­ny­lam is pur­su­ing la­bel ex­pan­sions of its On­pat­tro and Amvut­tra in AT­TR with car­diomy­opa­thy, as well.

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.

Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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BREAK­ING: Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck 5 years ago, where the soft spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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No­vavax shares shred­ded as Covid vac­cine sales fall more than 90% in Q2

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.