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.

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

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In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

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Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

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George Yancopoulos (Regeneron)

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Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

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Tuesday morning Inovio, which has been struggling to get its Covid-19 vaccine lined up for mass manufacturing, put out a release that touched on virtually every hot button in pandemic PR.

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Randy Schatzman, Bolt CEO (Bolt Biotherapeutics)

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