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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Scott Struthers, Crinetics CEO

Cri­net­ics spins out ra­dio­phar­ma ef­forts in­to a new com­pa­ny, high­light­ing the grow­ing field­'s al­lure

Largely known for its nonpeptide small molecule research, Crinetics has been keeping its radiopharma work comparatively under wraps. But that changed Monday afternoon as the California biotech spun out a new company focused solely on the burgeoning field.

Crinetics launched Radionetics after the closing bell Monday, the company announced, seeding the new entity with $30 million raised from 5AM Ventures and Frazier Healthcare Partners. Radionetics will start with its own radiopharma-centric platform and a pipeline of 10 programs aimed at solid tumors.

Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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