A gene therapy mystery? GenSight blasted as 1st PhIII eye study ends in an intriguing failure

April 4, 2018 05:41 AM EDTUpdated May 26, 08:50 PM

John Carroll

A gene therapy mystery? GenSight blasted as 1st PhIII eye study ends in an intriguing failure

GenSight has a gene therapy mystery on its hands, which is about the last thing it wanted at the end of Phase III.

Assessing the 48-week data from its first pivotal test of a treatment for Leber Hereditary Optic Neuropathy — or LHON, a rare genetic disease that causes blindness — investigators pulled out a meaningful improvement in sight in their one treated eye.

Bernard Gilly

The mystery: The other eyes that received a sham therapy did just as well with their eyesight. Exactly as well.

That makes the Phase III study of GS010 a failure, and rather than stay to try and solve the mystery, investors bailed, driving down the EuroNext stock $SIGHT down by 34%.

One of the reasons why the early gene therapy pioneers like GenSight picked hereditary eye diseases to go after first is that the eye is a contained unit, limiting off-target effects. But GenSight’s Paris-based CEO Bernard Gilly says that as only a fraction of patients historically see a spontaneous improvement in eyesight, he’s wondering if the therapy injected into one eye delivers an unexpected benefit to the other.

At the same time, GenSight touted a hit on a retinal biomarker for the disease, which they claimed as evidence that the therapy had an impact separate from the sham.

“The fact that structural measures of the retina showed such a large statistical difference with treatment is compelling and objective evidence that this gene therapy protects the integrity of many retinal ganglion cells from the damage of LHON,” commented company co-founder José-Alain Sahel.

That’s a messy argument, with the company arguing that it appeared the therapy improved sight for both eyes, but only hit the secondary biomarker in the treated eye.

The company — which tried and failed to make it onto Nasdaq — will be left looking for more data to analyze from its next two Phase III studies, which are upcoming. But easy explanations will be hard to come by.

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October 17, 2019 07:29 AM EDTUpdated 07:48 AM

John Carroll

R&D

The FDA will hustle up an expedited review for AstraZeneca’s next shot at a blockbuster cancer drug franchise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

October 17, 2019 07:00 AM EDTUpdated 08:45 AM

John Carroll

R&D

Startups

Sean Parker helps create a CRISPRed cell therapy 2.0 play — and he’s got a high-profile set of leaders on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.
The biotech started by putting together an “arsenal” of technologies aimed at making cell therapies for cancer much, much better than the rather crude first-generation drugs that hit the market from Novartis and Kite.
Their drugs have become the baseline against which all others are being measured.
“The technology set we’re developing is independent of the chassis,” Drazan tells me. “It doesn’t have to be autologous (extracted from the patient) or allogeneic (off the shelf). It doesn’t have to be a T cell, it could be a B cell.” But they are starting out on the autologous side, where they have the most knowledge and insight into manufacturing techniques.
It also doesn’t have to be close to the clinic.
Drazan expects the biotech will be working its way through preclinical operations for “a few years,” with enough money from the $85 million launch round to get into humans.
By today’s superheated fundraising standards, that’s not a huge amount of cash. Lyell, another cell therapy 2.0 startup we featured last week, raised $600 million in a year, including a big chunk of cash from GlaxoSmithKline. Drazan is interested in dealmaking as well, but he also knows he has the cash necessary to support the company for a good run — a key part of what it takes to bring together a stellar team of top players.

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October 16, 2019 07:54 AM EDT

John Carroll

R&D

Eli Lilly’s first PhIII showdown for their $1.6B cancer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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ENDPOINTS CAREERS

Medical Director to Senior Director Clinical Development - Neuromuscular Disorders / Spinal Muscular Atrophy

Biogen

Cambridge, Massachusetts, USA

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Swamy Vijayan. Plexium

October 17, 2019 06:45 AM EDT

Amber Tong

Startups

Venture

San Diego upstart debuts discovery engine that puts a twist to protein degradation

For years, the idea of protein degradation — utilizing the cell’s natural garbage disposal system to mark problematic proteins for destruction — remained an elegant but technically difficult concept. But now established as a promising clinical strategy, with major biopharma players such as Bayer, Gilead and Vertex trying to grab a foothold via partnership deals, a San Diego startup is looking to exploit it and push its limits.

October 16, 2019 10:07 AM EDT

John Carroll

Pharma

R&D

CSL accuses rival Pharming of participating in a scheme to rip off IP on HAE while recruiting senior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

October 14, 2019 05:16 PM EDT

John Carroll

[Video] Celebrating trial failures, changing the culture and allying with California dreamers: R&D chief Hal Barron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Medical animation: Making it easier for the site and the patient to understand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

ENDPOINTS CAREERS

Medical Director, Clinical Development – Pain

Biogen

Cambridge, Massachusetts, USA

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October 16, 2019 06:58 AM EDTUpdated 8 hours ago

John Carroll

Deals

R&D

UPDATED: Alexion pays $930M to buy out Achillion and its promising companion drug to Soliris

After a series of stock-crunching setbacks over the years, Achillion enjoyed a turn in the sun a few weeks ago as the FDA blessed their lead drug danicopan (ACH-4471) — a complementary therapy for PNH patients taking Alexion’s Soliris — with a breakthrough drug designation after taking a look at some solid supporting Phase II data.

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October 15, 2019 07:45 PM EDTUpdated 1 hour ago

John Carroll

R&D

The $102B club: The top 15 R&D spenders in the global biopharma business — 2019 edition

Over the past few years, the deluge of capital into biotech has helped lead to a dramatic shift in focus on new drug approvals, as startups are now able to raise enough cash to get through a pivotal and onto the market. But the top 15 players still account for $102 billion in spending, and their successes and failures continue to determine just how productive the industry is.

Recently we’ve seen a number of new R&D chiefs take their places at the Big 15, either setting the stage for a more focused R&D strategy — often playing more heavily in oncology. That’s true for AstraZeneca, which has had some landmark successes, and GSK, which is in search of its own turnaround in pharma R&D. HIV and vaccines are separate from that group, now led by Hal Barron.

I’ve made a point of watching their track record every year for more than a decade now. What follows is intended as a broad gauge of their activity. You don’t have to have a lot of major successes to score a winning record here, but it’s virtually impossible without a blockbuster or three in the pipeline.

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