Nancy Yu (RDMD)

Abun­dant fund­ing, sparse da­ta: San Fran­cis­co start­up backs 're­al world' mod­el for rare dis­ease drug de­vel­op­ment

Rare dis­eases, a field of drug de­vel­op­ment where fund­ing far out­strips re­search on of­ten poor­ly un­der­stood con­di­tions, can leave sci­en­tists of­ten rein­vent­ing the wheel to en­gi­neer ther­a­peu­tics.

RD­MD, a San Fran­cis­co-based com­pa­ny, has a plan to ad­dress that im­passe by serv­ing as a con­duit be­tween the pa­tient and the drug de­vel­op­er. The plat­form courts pa­tients with rare dis­eases by help­ing them ac­cess med­ical records and par­tic­i­pate in re­search, while for drug de­vel­op­ers, the com­pa­ny struc­tures the com­piled da­ta in an ef­fort to build re­search pro­grams and de­vel­op an ev­i­dence base palat­able for reg­u­la­to­ry au­thor­i­ties.

Un­til now, com­pa­nies big and small in the space have been stuck look­ing for pa­tients in 10, 20 or more hos­pi­tals, de­pend­ing on the dis­ease, not­ed co-founder Nan­cy Yu in an in­ter­view.

“So most com­pa­nies are grow­ing their in­ter­nal teams, as well as work­ing with con­tract re­search or­ga­ni­za­tions, and sub­con­tract­ing to up to some­times 15 dif­fer­ent soft­ware ven­dors to man­age the process,” Yu said.

Stream­lin­ing this process, and help­ing pa­tients them­selves ac­cess their da­ta and par­tic­i­pate in re­search, could change the way the rare dis­ease drug de­vel­op­ment is con­duct­ed, RD­MD hopes. This lofty goal was giv­en a $14 mil­lion in­jec­tion on Thurs­day in a Se­ries A round led by Spark Cap­i­tal, a ven­ture cap­i­tal firm that has pre­vi­ous­ly backed com­pa­nies such as Slack, Twit­ter and Ocu­lus.

“At the end of the day, rare dis­ease just re­quires a dif­fer­ent mod­el for drug de­vel­op­ment,” Yu said. “The chal­lenge is re­al­ly un­der­stand­ing what the dis­ease ac­tu­al­ly is and how you can best cre­ate and de­sign a pro­gram around ev­i­dence that ex­ists. It’s re­al­ly hard to de­sign a suc­cess­ful pro­gram if you don’t know much about the dis­ease.”

That re­quires pa­tient da­ta which, apart from be­ing scarce, are not all ac­ces­si­ble in one uni­ver­sal elec­tron­ic med­ical records sys­tem.

“So we get per­mis­sion from pa­tients … to be able to get all their records from their var­i­ous fa­cil­i­ties. And that’s both be­cause we want to em­pow­er pa­tients with that choice of opt­ing in to par­tic­i­pate in re­search, but it’s al­so a ne­ces­si­ty op­er­a­tional­ly for us to be able to get that in­for­ma­tion, be­cause it doesn’t sit in a cen­tral data­base some­where,” she said.

With the pa­tient’s con­sent, the da­ta are then col­lat­ed and dis­sem­i­nat­ed to com­pa­nies to give them a com­pre­hen­sive un­der­stand­ing of the dis­ease, and con­se­quent­ly, de­sign clin­i­cal tri­als, de­ter­mine what end­points and bio­mark­ers are rel­e­vant, and even ed­u­cate pay­ers and in­sur­ance com­pa­nies so they can cov­er the drugs up­on ap­proval.

There’s a lot that pa­tients can con­tribute to in terms of re­search that doesn’t nec­es­sar­i­ly in­volve par­tic­i­pat­ing in a clin­i­cal tri­al, she added.

“For ex­am­ple, some of this da­ta could be used to sup­port and elim­i­nate the need for a place­bo con­trol arm be­cause you’re just look­ing at da­ta that al­ready ex­ists in the re­al world around pa­tients and their nat­ur­al pro­gres­sion of dis­ease,” Yu said. “And so that’s cer­tain­ly some­thing that every­one is very fo­cused on and hop­ing to use the da­ta for.”

Sound fa­mil­iar? A New York-based tech com­pa­ny called Flat­iron Health that was swal­lowed by Swiss gi­ant Roche in 2018, has sim­i­lar plans to use re­al-world ev­i­dence to re­place more tra­di­tion­al clin­i­cal tri­al da­ta to help the FDA make de­ci­sions for can­cer drugs.

But tra­di­tion­al ran­dom­ized con­trolled tri­als (RCTs) are con­sid­ered the gold stan­dard to prove if a com­pound or in­ter­ven­tion is safe and ef­fec­tive for its in­tend­ed use — they are used to show that a ben­e­fit or ad­verse event ob­served is not a mat­ter of chance or bias.

But giv­en lim­i­ta­tions such as strict in­clu­sion cri­te­ria, which typ­i­cal­ly dis­qual­i­fy old­er pa­tients and those suf­fer­ing from co-mor­bidi­ties, RCTs can be an in­ac­cu­rate rep­re­sen­ta­tion of pa­tients in the re­al world. But skep­tics crit­i­cize that re­ly­ing sole­ly on re­al-world ev­i­dence could be dan­ger­ous, as the process has the po­ten­tial to in­tro­duce re­searcher bi­as­es, and is not sub­ject to the same method­olog­i­cal rig­or.

That be­ing said, un­like can­cer drug de­vel­op­ment, rare dis­ease tri­als are of­ten ham­pered by slow en­roll­ment due to the scarci­ty of pa­tients — and the FDA re­quires a much small­er body of ev­i­dence for de­ci­sion mak­ing. Sarep­ta Ther­a­peu­tics’ pi­o­neer­ing Duchenne mus­cu­lar dy­s­tro­phy (DMD) drug Ex­ondys 51, for in­stance, was ap­proved on the ba­sis of a tiny non-place­bo con­trolled tri­al that com­pared the ef­fect of the drug to the nat­ur­al course of the dis­ease.

De­spite stiff op­po­si­tion from with­in and out­side the agency from crit­ics who said da­ta were in­suf­fi­cient to war­rant ap­proval, the FDA cleared the drug for use in a sub­set of pa­tients with the rare mus­cle-wast­ing dis­ease in 2016, prompt­ing some to sug­gest the agency had bowed to pres­sure from pa­tient ad­vo­cates. On­ly in 2019 did Sarep­ta sub­mit plans for a con­fir­ma­to­ry tri­al, which is ex­pect­ed to be com­plet­ed by 2024. But in the mean­time, the com­pa­ny has since se­cured an­oth­er DMD ap­proval on the ba­sis of a 24 pa­tient study.

Yu, who pre­vi­ous­ly worked with con­sumer ge­net­ics com­pa­ny 23andme, set up RD­MD in late 2017 soon af­ter co-founder On­no Faber was di­ag­nosed with a rare ge­net­ic dis­ease called NF2 (Neu­rofi­bro­mato­sis Type 2), which af­fects 1 in 30,000 peo­ple.

“And so when we got to­geth­er, it was re­al­ly to fig­ure out how do we tack­le this — there are 7000 con­di­tions and like one in 10 peo­ple have a rare dis­ease that in ag­gre­gate, it’s a re­al­ly big prob­lem,” she not­ed.

On Thurs­day, the com­pa­ny al­so un­veiled a part­ner­ship with Bel­gium-based drug­mak­er UCB for up to five years to work on pro­gres­sive supranu­clear pal­sy (PSP), a rare neu­rode­gen­er­a­tive dis­ease.

In ad­di­tion, RD­MD is al­so part­ner­ing with pa­tient ad­vo­ca­cy or­ga­ni­za­tions and physi­cian con­sor­tiums across 12 con­di­tions, in­clud­ing the Chil­dren’s Tu­mor Foun­da­tion, Cure San­fil­ip­po Foun­da­tion and Na­tion­al Tay-Sachs & Al­lied Dis­eases As­so­ci­a­tion.

The Se­ries A round al­so in­clud­ed the par­tic­i­pa­tion of ex­ist­ing seed in­vestors Lux Cap­i­tal, Vil­lage Glob­al and Garu­da Ven­tures, and new in­vestor Maveron. The mon­ey will be used, among oth­er things, to ex­pand in­to a fur­ther 20 rare con­di­tions and en­sure the con­ti­nu­ity of re­search pro­grams through­out the Covid-19 pan­dem­ic.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Vas Narasimhan (Photographer: Jason Alden/Bloomberg via Getty Images)

No­var­tis de­tails plans to axe 8,000 staffers as Narasimhan be­gins sec­ond phase of a glob­al re­org

We now know the number of jobs coming under the axe at Novartis, and it isn’t small.

The pharma giant is confirming a report from Swiss newspaper Tages-Anzeiger that it is chopping 8,000 jobs out of its 108,000 global staffers. A large segment will hit right at company headquarters in Basel, as CEO Vas Narasimhan axes some 1,400 of a little more than 11,000  jobs in Switzerland.

The first phase of the work is almost done, the company says in a statement to Endpoints News. Now it’s on to phase two. In the statement, Novartis says:

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Lina Gugucheva, NewAmsterdam Pharma CBO

Phar­ma group bets up to $1B-plus on the PhI­II res­ur­rec­tion of a once dead-and-buried LDL drug

Close to 5 years after then-Amgen R&D chief Sean Harper tamped the last spade of dirt on the last broadly focused CETP cholesterol drug — burying their $300 million upfront and the few remaining hopes for the class with it — the therapy has been fully resurrected. And today, the NewAmsterdam Pharma crew that did the Lazarus treatment on obicetrapib is taking another big step on the comeback trail with a €1 billion-plus regional licensing deal, complete with close to $150 million in upfront cash.

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How pre­pared is bio­phar­ma for the cy­ber dooms­day?

One of the largest cyberattacks in history happened on a Friday, Eric Perakslis distinctly remembers.

Perakslis, who was head of Takeda’s R&D Data Sciences Institute and visiting faculty at Harvard Medical School at the time, had spent that morning completing a review on cybersecurity for the British Medical Journal. Moments after he turned it in, he heard back from the editor: “Have you heard what’s going on right now?”

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Scoop: Roche scraps one of two schiz­o­phre­nia PhII tri­als af­ter fail­ing the pri­ma­ry end­point

Roche has terminated one of two Phase II trials testing its drug ralmitaront in patients with schizophrenia, the Big Pharma confirmed to Endpoints News.

The study was terminated last month, according to a June 22 update to the registry on clinicaltrials.gov. Begun in September 2020, the trial was looking at ralmitaront in patients with acute schizophrenia. The trial enrolled 286 patients out of an originally planned 308.

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Pearl Huang, Dunad Therapeutics CEO (Ken Richardson, PR Newswire)

Long­time biotech leader Pearl Huang takes the reins as CEO of No­var­tis-backed up­start

It has only been a few months since Pearl Huang exited the top seat at Cygnal Therapeutics, but now she’s back at the helm of another biotech.

After taking a few months off — passing an exam in that time to get her captain’s license from the US Coast Guard — she’s been named CEO of Dunad Therapeutics, a biotech focused on developing a small molecule covalent therapies that was founded in 2020. Huang told Endpoints News that two factors attracted her to going back to the c-suite: the company’s technology and its co-founders.

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(AP Photo/Gemunu Amarasinghe)

Some phar­ma com­pa­nies promise to cov­er abor­tion-re­lat­ed trav­el costs — while oth­ers won't go that far yet

As the US Department of Health and Human Services promises to support the millions of women who would now need to cross state lines to receive a legal abortion, a handful of pharma companies have said they will pick up employees’ travel expenses.

GSK, Sanofi, Johnson & Johnson, BeiGene, Alnylam and Gilead have all committed to covering abortion-related travel expenses just four days after the Supreme Court overturned Roe v. Wade and revoked women’s constitutional right to an abortion.

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Aurobindo Pharma co-founders P. V. Ram Prasad Reddy (L) and K. Nityananda Reddy

Au­robindo Phar­ma re­ceives warn­ing let­ter from In­di­a's SEC fol­low­ing more FDA ques­tion marks

Indian-based generics manufacturer Aurobindo Pharma has been in the crosshairs of the FDA for several years now, but the company is also attracting attention from regulators within the subcontinent.

According to the Indian business news site Business Standard, a warning letter was sent to the company from the Securities Exchange Board of India, or SEBI.

The letter is related to disclosures made by the company on an ongoing FDA audit of the company’s Unit-1 API facility in Hyderabad, India as well as observations made by the US regulator between 2019 and 2022.

David Veitch, Basilea CEO

Basilea toss­es an on­col­o­gy drug back to Mer­ck, dou­bling down on an­tibi­otics in re­vamp

Swiss biotech Basilea Pharmaceutica has shed one of its last pipeline ties with oncology as it makes a move to concentrate on antibiotics in a race to profitability next year. And they’ve followed up on that with news of a Phase III success they believe can help expand prospects for a key franchise player.

The company put out word on Monday that the execs are handing rights to the FGFR inhibitor derazantinib back to Merck by the end of this year as it shuts down clinical work on the tumor checkpoint controller lisavanbulin. They’re still working on partnering that out along with their TTK/PLK1-inhibitor BAL0891 and preclinical oncology assets.