FDA ex­pert pan­el unan­i­mous­ly rec­om­mends ap­proval for Hori­zon Ther­a­peu­tics eye drug

An FDA ad­vi­so­ry com­mit­tee not­ed with con­cern a small safe­ty data­base but unan­i­mous­ly en­dorsed a Hori­zon Ther­a­peu­tics drug for a rare eye au­toim­mune dis­ease that can blind pa­tients: tepro­tu­mum­ab for thy­roid eye dis­ease (TED).

“It was a pret­ty easy vote,” said Er­i­ca Brit­tain, an NIH bio­sta­tis­ti­cian and one of the 12 pan­elists on FDA’s Der­ma­to­log­ic and Oph­thalmic Drugs Ad­vi­so­ry Com­mit­tee.

Af­ter lis­ten­ing to tes­ti­mo­ny from pa­tients and ad­vo­cates, the ad­vis­ers de­bat­ed the drug’s la­bel and whether there was enough da­ta to prop­er­ly un­der­stand the drug’s ad­verse ef­fects, but rarely showed the kind of alarm that would lead to a ‘no’ vote.  Hori­zon sub­mit­ted a Phase III tri­al show­ing that the drug could dra­mat­i­cal­ly low­er prop­to­sis, or bulging of the eye, by at least 2 mm in 89.2% of pa­tients, but be­tween the Phase III and the Phase II there were less than 90 pa­tients ac­tu­al­ly treat­ed with a pro­fu­sion.

“The un­cer­tain­ty lies in the small pa­tient pop­u­la­tion and po­ten­tial risk of side ef­fects,” said Tim­o­thy Mur­ray, a pan­elist and di­rec­tor of Mi­a­mi Oc­u­lar On­col­o­gy and Reti­na. But “this is one of the more re­mark­able drugs to come out of an un­met need.”

The FDA had raised con­cerns about how the pri­ma­ry end­point in Hori­zon’s Phase III was cal­cu­lat­ed, but that did not seem to be a ma­jor is­sue for the pan­el. Like the FDA, they de­ter­mined the biotech nev­er­the­less showed strong ef­fi­ca­cy and spent much of the ses­sion de­bat­ing how a post-ap­proval study should be con­struct­ed. Hori­zon had pro­posed a reg­istry of 200 pa­tients but some ex­perts want­ed 500.

The PDU­FA date is set for March 8.  The FDA does not have to lis­ten to the rec­om­men­da­tions but gen­er­al­ly does.

Hori­zon has pro­ject­ed $750 mil­lion in peak sales for the drugs, while an­a­lysts have pegged the num­ber clos­er to $500 mil­lion. It would be a sig­nif­i­cant win for the com­pa­ny and end a long road for an an­ti­body that be­gan life as a Roche-li­censed treat­ment for sol­id tu­mors. Hori­zon pur­chased it two years ago from Nar­row Vi­sion for $145 mil­lion up­front two years ago.

The com­pa­ny ex­pects to treat around 15,000 to 20,000 TED pa­tients per year. The au­toim­mune dis­ease pri­mar­i­ly af­fects women and man­i­fests in midlife and can se­vere­ly hand­i­cap peo­ple.

Pa­tient and pa­tient ad­vo­cates tes­ti­fied be­fore the FDA ad­vi­sors’ dis­cus­sion, and the pan­elists cit­ed their words when ex­plain­ing their vote.  Pa­tients talked about the dis­ease ren­der­ing them un­able to dri­ve or do dai­ly tasks, while al­so chang­ing their ap­pear­ance.

I wel­come the ad­di­tion of this drug to our ar­ma­men­tar­i­um to treat this hor­ri­ble, hor­ri­ble dis­ease,” said John Stam­ler, a Uni­ver­si­ty of Iowa oph­thal­mol­o­gist and pan­elist. “It may be the on­ly ar­row in our quiver.”

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,800+ biopharma pros reading Endpoints daily — and it's free.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,800+ biopharma pros reading Endpoints daily — and it's free.

US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,800+ biopharma pros reading Endpoints daily — and it's free.

Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Clockwise from left: Canaccord Genuity principal Michelle Gilson, Canaccord Genuity CSO Brian Mueller and BioMarin CSO Hank Fuchs (Canaccord Genuity webcast)

Bio­Marin CSO diss­es ri­vals for the he­mo­phil­ia A gene ther­a­py crown: Way be­hind, fac­ing big re­cruit­ment chal­lenges and at best a .6 on the gen-one scale

The leader in the race to a hemophilia A gene therapy does not like to be compared unfavorably to the competition. And when their top execs do the comparing, don’t look for any modesty — BioMarin, they say, owns the lead.

As Factor VIII expression wanes over time, quite a few analysts have raised questions about the kind of future BioMarin’s gene therapy — a supposed once-and-done treatment — faces if it stops working. But just 7 days away from their PDUFA date, with high odds of success, the top execs clearly feel that they are way out front, while promising their rivals will discover there’s a tough slog ahead trying to pursue trials where large numbers of patients are ineligible for new therapies.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

James Wilson, WuXi Global Forum at JPM20

FDA puts up a red light for Pas­sage Bio’s first gene ther­a­py pro­gram, de­lay­ing a pro­gram from James Wilson's group at Penn

Gene therapy pioneer James Wilson spearheaded animal studies demonstrating the potential of new treatments injected directly into the brain, looking to jumpstart a once-and-done fix for an extraordinarily rare disease called GM1 gangliosidosis in infants. His team at the University of Pennsylvania published their work on monkeys and handed it over to Passage Bio, a Wilson-inspired startup building a pipeline of gene therapies — with an IND for PBGM01 to lead the way.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,800+ biopharma pros reading Endpoints daily — and it's free.

Silviu Itescu, Mesoblast CEO

FDA's ODAC shrugs off ob­jec­tions to Mesoblast's GVHD drug for chil­dren, vot­ing 9-1 in fa­vor and im­prov­ing the odds of an ap­proval

The FDA’s Oncologic Drugs Advisory Committee once again waved through an investigational drug, clearing the potential final hurdle before the agency’s decision.

Thursday’s winner was Mesoblast $MESO, an Australian stem-cell company that submitted its Ryoncil drug for the treatment of steroid refractory acute graft-versus-host disease in children younger than 12. ODAC gave Ryoncil the thumbs up by a 9-1 vote, shrugging off concerns about trial design and pushing aside the need for an additional study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,800+ biopharma pros reading Endpoints daily — and it's free.