San­ther­a's Duchenne ef­fort gets a boost on pos­i­tive PhI­Ia for al­ter­na­tive steroid va­morolone — though there's a lot left to prove

Months af­ter San­thera got its hands on a sec­ond Duchenne mus­cu­lar dy­s­tro­phy drug, the Swiss com­pa­ny is get­ting an ear­ly look at how it im­proves mus­cle func­tion. But se­ri­ous ques­tions re­main as it takes on a field stuffed with en­trenched ri­vals and con­tro­ver­sy.

Er­ic Hoff­man

Rever­a­Gen was in charge of the Phase IIa ex­ten­sion, which com­pared dif­fer­ent dos­es of va­morolone with nat­ur­al his­to­ry con­trols. With 12 boys (aged 4 to 7) in each of four treat­ment groups, in­ves­ti­ga­tors test­ed 0.25, 0.75, 2.0 and 6.0 mg/kg/day in the study and pub­lished the re­sults in Neu­rol­o­gy.

With­out spelling out num­bers, the com­pa­ny not­ed that pa­tients reg­is­tered sta­tis­ti­cal­ly sig­nif­i­cant and pro­por­tion­al im­prove­ments from base­line on mul­ti­ple fronts, in­clud­ing the pri­ma­ry end­point of time to stand from supine. Sec­ondary end­points re­gard­ing mo­tor func­tion out­comes span time to run/walk 10 me­ters, time to climb stairs, 6-minute walk test and North Star Am­bu­la­to­ry Test — with the high­est dose out­per­form­ing the low­est in a no­table man­ner.

Per­haps more im­por­tant­ly to their point, Rever­a­Gen re­port­ed that va­morolone ap­pears to trig­ger less adren­al sup­pres­sion, in­sulin re­sis­tance and bone mor­bidi­ties nor­mal­ly ob­served with oth­er cor­ti­cos­teroids.

“Based on these da­ta, va­morolone has po­ten­tial to re­place stan­dard cor­ti­cos­teroids cur­rent­ly used in pa­tients with DMD,” Rever­a­Gen CEO said in a state­ment.

Thomas Meier

Cor­ti­cos­teroids such as pred­nisone and de­flaza­cort rep­re­sent the fun­da­men­tal DMD treat­ments, pro­vid­ing a point of ref­er­ence for new and ex­per­i­men­tal ther­a­pies. They are al­so dirt cheap, un­til Marathon ac­quired rights to de­flaza­cort, rushed it through an FDA ap­proval as Em­flaza and jacked up the price from rouhg­ly $1,000 to $89,000 in a no­to­ri­ous case of price goug­ing. The avail­abil­i­ty of pred­nisone at pen­nies per pill, though, keeps the bar high on any re­place­ment.

When San­thera ac­quired Idor­sia’s op­tion for va­morolone late last year (in ex­change for $20 mil­lion up­front and 1 mil­lion shares), CEO Thomas Meier high­light­ed how it fits in­to their port­fo­lio strat­e­gy to cov­er a broad Duchenne pa­tient spec­trum, “ir­re­spec­tive of ge­net­ic back­ground, dis­ease stage or age.” That’s in con­trast with the tar­get­ed ap­proach­es oth­ers such as Sarep­ta and start­up Ex­on­ics have tak­en, with their re­spec­tive ex­on-skip­ping and gene edit­ing ef­forts.

It has not worked out smooth­ly, though. San­thera’s oth­er Duchenne can­di­date, idebenone, has pre­vi­ous­ly been de­nied ac­cel­er­at­ed ap­proval by the FDA and slapped down by the EMA. (The drug is mar­ket­ed as Rax­one in Eu­rope to treat Leber’s hered­i­tary op­tic neu­ropa­thy.)

But San­thera has since man­aged to notch or­phan drug des­ig­na­tions on both sides of the At­lantic and kick­start­ed a Phase III tri­al eval­u­at­ing the ef­fi­ca­cy of idebenone in de­lay­ing the loss of res­pi­ra­to­ry func­tion in Duchenne pa­tients al­ready re­ceiv­ing cor­ti­cos­teroids.

Mean­while, Rever­a­Gen is in the midst of a Phase IIb study with 120 cor­ti­cos­teroid-naive boys, com­par­ing the two high­est dos­es of va­morolone (2.0 and 6.0 mg/kg/day) with pred­nisone and place­bo. It’s slat­ed to con­clude next year.

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Joe Jimenez, Getty

Ex-No­var­tis CEO Joe Jimenez is tak­ing an­oth­er crack at open­ing a new chap­ter in his ca­reer — and that in­cludes a new board seat and a $250M start­up

Joe Jimenez is back.

The ex-CEO of Novartis has taken a board seat on Century Therapeutics, the Versant and Bayer-backed startup focused on coming up with a brand new twist on cell therapies for cancer — a field where Jimenez made his mark backing the first personalized CAR-T approved for use.

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Can we make the an­tibi­ot­ic mar­ket great again?

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

Top Har­vard chemist caught up in FBI’s 'T­hou­sand Tal­ents' drag­net, ac­cused of ly­ing about Chi­nese con­nec­tions, pay

The FBI’s probe into the alleged theft of R&D secrets by Chinese authorities has drawn Harvard’s top chemist into its net.

The agency accused Charles M. Lieber, who chairs the university’s chemistry and chemical biology department, with lying about his involvement in China’s Thousand Talents campaign, which was established as a way of drawing in innovators from around the world. And the scientist, 60, was charged with making false statements about his ties to China.

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Eye­ing a trio of tri­al ini­ti­a­tions, Jim Wilson's gene ther­a­py start­up woos Bruce Gold­smith from Deer­field as CEO

Passage Bio — Jim Wilson’s self-described “legacy company” — has wooed a seasoned biotech executive to steer the clinical entry of its first three gene therapy programs.

Bruce Goldsmith jumps to the helm of Passage after a brief CEO stint at Civetta, a cancer-focused startup he helped launch while a venture partner at Deerfield. He takes over from OrbiMed partner and interim chief Stephen Squinto, who will now lead the R&D team.

Amber Saltzman (Ohana)

Flag­ship's first ven­ture of 2020 is out, and it's all about sperm

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”

Pfiz­er ax­es 6 ear­ly to late-stage can­cer stud­ies from the pipeline — with one oth­er cut for sick­le cell dis­ease

Pfizer trimmed a group of 3 R&D programs using their PD-L1 Bavencio — partnered with Merck KGaA — in their latest pipeline cull.

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The FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. They plan to squash it — and per­ma­nent­ly ex­ile him

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

UP­DAT­ED: Ac­celeron res­ur­rects block­buster hopes for so­tater­cept with pos­i­tive PhII — and shares rock­et up

Acceleron $XLRN says that its first major trial readout of 2020 is a success.

In a Phase II study of 106 patients with pulmonary arterial hypertension (PAH), Acceleron’s experimental drug sotatercept hit its primary endpoint: a significant reduction in pulmonary vascular resistance. The drug also met three different secondary endpoints, including the 6-minute walking test.

“We’re thrilled to report such positive topline results from the PULSAR trial,” Acceleron CEO Habib Dable said in a statement. The company said in a conference call they plan on discussing a Phase III trial design with regulators.

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