Mag­gie Carmichael wasn’t de­vel­op­ing like oth­er kids. As a tod­dler, she wasn’t walk­ing and had a lim­it­ed vo­cab­u­lary for her age.

She was di­ag­nosed with PMM2-CDG, po­ten­tial­ly fa­tal gene mu­ta­tions that cause ab­nor­mal en­zyme ac­tiv­i­ty — and af­fect few­er than 1,000 peo­ple world­wide. Her par­ents, Hol­ly and Dan Carmichael, raised $250,000 for sci­en­tists to screen ex­ist­ing drugs to find a po­ten­tial treat­ment, and in a sin­gle-pa­tient tri­al with Mag­gie as the test sub­ject, one drug showed promis­ing re­sults. The young girl stopped face-plant­i­ng when crawl­ing, she be­gan us­ing a walk­er in­stead of her wheel­chair, and her lex­i­con ex­pand­ed.

The Carmichaels and their or­ga­ni­za­tion, Mag­gie’s Cure, could have hand­ed off the work to a biotech com­pa­ny. In­stead, the fam­i­ly from Stur­gis, Michi­gan, formed a joint ven­ture part­ner­ship with Per­lara PBC, a San Fran­cis­co com­pa­ny that tries to iden­ti­fy new and ex­ist­ing drugs to treat rare dis­eases. The Mayo Clin­ic would lat­er join as a co-own­er of Mag­gie’s Pearl.

The com­pa­ny se­cured ap­proval last De­cem­ber for a 40-pa­tient clin­i­cal tri­al that could one day lead the FDA to ap­prove the drug for PMM2-CDG. It would al­so de­fy what doc­tors told the Carmichaels about the prospects of a treat­ment when Mag­gie was di­ag­nosed at 9 months:

“Not a snow­ball’s chance in hell.”

Half of all rare-dis­ease pa­tients are chil­dren, and their fam­i­lies have long pushed to speed up cures, usu­al­ly by form­ing foun­da­tions that seed mon­ey for re­search. If there are promis­ing find­ings, many hand the work off to biotech com­pa­nies to de­vel­op treat­ments. Now, some fam­i­lies are form­ing their own biotech busi­ness­es, act­ing as drug de­vel­op­ers to find treat­ments for ul­tra-rare dis­eases that af­fect 1,000 pa­tients or few­er.

But their chances are slim.

On­ly about 12% of drugs in clin­i­cal tri­als are ever ap­proved by the FDA. And few biotech firms fo­cus on rare dis­eases giv­en the lim­it­ed size of the pa­tient mar­ket; 12% of clin­i­cal tri­als are fo­cused on rare dis­eases.

This means fam­i­lies aren’t like­ly to find a cure — let alone make a prof­it.

“If a drug should get ap­proved for a dis­ease with 1,000 pa­tients, the prob­a­bil­i­ty that there are any ma­te­r­i­al prof­its, I would say, is ac­tu­al­ly re­mote,” said James Ger­aghty, who is on biotech boards and is the au­thor of “In­side the Or­phan Drug Rev­o­lu­tion: The Promise of Pa­tient-Cen­tered Biotech­nol­o­gy.”

But fam­i­lies say cures, not prof­its, mo­ti­vate them.

Ac­cord­ing to the Na­tion­al In­sti­tutes of Health, there are rough­ly 7,000 rare dis­eases, af­fect­ing near­ly 1 in 10 Amer­i­cans. A rare dis­ease is gen­er­al­ly con­sid­ered one that af­fects few­er than 200,000 peo­ple in the US at a giv­en time. On­ly 30% of chil­dren with rare dis­eases will live to see their 5th birth­day.

Some 95% of rare dis­eases are with­out an FDA-ap­proved treat­ment or ther­a­py.

Up­on a child’s di­ag­no­sis, par­ents will of­ten quit their jobs and re­order their lives to find a treat­ment. Fam­i­lies will use their own mon­ey or raise funds to en­ter the are­na. Dozens, if not hun­dreds, of non­prof­it fam­i­ly foun­da­tions across the na­tion fo­cus on rare-dis­ease treat­ments amid the dearth of pub­lic and pri­vate fund­ing.

Joe Panet­ta

Drug­mak­ers can charge ex­or­bi­tant prices for rare-dis­ease drugs, so it can be high­ly prof­itable to tar­get rare dis­eases like cys­tic fi­bro­sis, which af­fects up to 200,000 Amer­i­cans. But the mar­ket be­comes much less at­trac­tive for ul­tra-rare dis­eases be­cause of the much small­er pool of pa­tients.

“It’s the riski­est of the risky,” said Joe Panet­ta, CEO of Bio­com Cal­i­for­nia, a life sci­ences trade group.

Drug reg­u­la­tions pro­hib­it the Carmichaels from shar­ing how Mag­gie is do­ing now be­cause of the clin­i­cal tri­al, but Mag­gie’s Pearl, as­sum­ing its drug earns FDA ap­proval, says it aims to en­sure the treat­ment can be ac­cessed by all with the dis­ease.

The Carmichael fam­i­ly is help­ing to pay for a clin­i­cal tri­al it es­ti­mates will cost $3 mil­lion to $5 mil­lion. The fam­i­ly won’t say how much it’s con­tribut­ing, but $2 mil­lion is com­ing from a fed­er­al Small Busi­ness In­no­va­tion Re­search grant.

Hol­ly Carmichael, chief op­er­at­ing of­fi­cer of Mag­gie’s Pearl, says she’s mo­ti­vat­ed to shep­herd a drug’s de­vel­op­ment while keep­ing prices low­er than they might oth­er­wise be. “We’re not a tra­di­tion­al biotech with share­hold­ers that have cer­tain prof­it thresh­olds,” she said.

The com­pa­ny has pledged to rein­vest a por­tion of its prof­its in­to re­search and de­vel­op­ment. The rest would flow to the ven­ture’s own­ers, in­clud­ing the Carmichael fam­i­ly.

Ethan Perl­stein

In that way, Mag­gie’s Pearl is “just like any oth­er busi­ness,” said Ethan Perl­stein, the CEO of Mag­gie’s Pearl and Per­lara, which counts Swiss drug gi­ant No­var­tis AG and en­tre­pre­neur Mark Cuban among its ear­ly in­vestors. Con­vict­ed phar­ma­ceu­ti­cal ex­ec­u­tive Mar­tin Shkre­li was bought out of his ear­ly stake in Perl­stein’s ven­ture.

Last month, a Boston com­pa­ny called Vibe Biotech­nol­o­gy an­nounced a cryp­tocur­ren­cy-based mod­el to raise mon­ey for rare-dis­ease drug de­vel­op­ment. In­vestors will have the pow­er to vote on rare-dis­ease re­search pro­pos­als, and pa­tients’ fam­i­lies have own­er­ship stakes in promis­ing ther­a­pies.

“The chal­lenge for rare dis­eases isn’t nec­es­sar­i­ly find­ing a treat­ment — it’s fund­ing it,” said Alok Tayi, CEO and co-founder of Vibe Biotech­nol­o­gy, in a state­ment. “For the first time, Vibe Bio is giv­ing pa­tients with rare and over­looked dis­eases ac­cess to the fund­ing and com­mu­ni­ty sup­port they need to de­vel­op cures and own­er­ship over the re­sults.”

Alok Tayi

The com­pa­ny has launched two biotech com­pa­nies in part­ner­ship with two foun­da­tions: Chelsea’s Hope, which is fo­cused on Lafo­ra dis­ease, a fa­tal form of pro­gres­sive my­oclonus epilep­sy, and NF2 BioSo­lu­tions, which hopes to ac­cel­er­ate a gene ther­a­py for neu­rofi­bro­mato­sis Type 2, which caus­es the growth of non­cancer­ous tu­mors in the ner­vous sys­tem.

One rea­son more fam­i­lies strike out on their own is for greater con­trol.

Typ­i­cal­ly, if re­search ad­vances far enough, fam­i­lies en­trust biotech com­pa­nies to bring drugs to mar­ket. A com­pa­ny usu­al­ly gains in­tel­lec­tu­al prop­er­ty rights as part of tak­ing on the fi­nan­cial risks of de­vel­op­ing such treat­ments. But if that com­pa­ny shelves the pro­gram, par­ents are left help­less and heart­bro­ken.

The Cure Mi­to Foun­da­tion — along with oth­er fam­i­ly foun­da­tions — fund­ed re­search in Steven Gray’s lab at the Uni­ver­si­ty of Texas South­west­ern Med­ical Cen­ter.

Taysha Gene Ther­a­pies, a com­pa­ny formed in 2019, pledged to ac­cel­er­ate Gray’s re­search and take fi­nan­cial pres­sure off fam­i­lies. In re­turn, Taysha gained po­ten­tial­ly lu­cra­tive re­search li­cens­es and con­trols the rights to these pro­grams.

In March, Taysha an­nounced it would cut 35% of its staff and shelve much of its port­fo­lio, re­flect­ing an in­dus­try down­turn. The pause in­clud­ed Cure Mi­to’s cam­paign to de­vel­op a treat­ment for Leigh syn­drome, a neu­ro­gen­er­a­tive con­di­tion that leaves some chil­dren un­able to walk and breathe on their own.

Taysha’s pause has worn on Court­ney Bog­gs, a mem­ber of the Cure Mi­to Foun­da­tion. Her daugh­ter, Em­ma, is a cheer­ful 6-year-old who loves read­ing and play­ing with dolls. She eats through a feed­ing tube and can­not walk unas­sist­ed, and her con­di­tion will wors­en with­out treat­ment.

“We need some­thing for our kids, and not just our kids, but fu­ture gen­er­a­tions,” said Bog­gs, who lives in El Pa­so, Texas.

Taysha, which is among a small num­ber of com­pa­nies in­vest­ing in treat­ments for ul­tra-rare dis­ease, nar­rowed its fo­cus from more than 20 to four rare-drug pro­grams.

“We share the dis­ap­point­ment and frus­tra­tion of our pa­tients and their fam­i­lies right now,” the com­pa­ny said, “but tru­ly be­lieve the tough de­ci­sions we are mak­ing to­day will best po­si­tion us to con­duct new tri­als in the fu­ture.”

Oth­er fam­i­lies are try­ing to pre­vent that sce­nario by se­cur­ing more fa­vor­able terms when do­ing busi­ness with biotech com­pa­nies, such as li­cens­ing pay­ments and the abil­i­ty to claw back rights to med­ica­tions if drug­mak­ers take too long.

Craig Ben­son, a fi­nance ex­ec­u­tive from Austin, Texas, and his wife, Char­lotte, formed the Be­yond Bat­ten Dis­ease Foun­da­tion to find a treat­ment for their 19-year-old daugh­ter, Chris­tiane, who suf­fers from Bat­ten dis­ease, which caus­es vi­sion loss and seizures.

The Ben­sons’ foun­da­tion fund­ed a ther­a­py that the French phar­ma­ceu­ti­cal com­pa­ny Ther­anexus li­censed in 2020 and is in ear­ly-stage clin­i­cal tri­als. As part of the deal, Ther­anexus shoul­dered de­vel­op­ment costs and paid the foun­da­tion an undis­closed up­front sum. The foun­da­tion may re­ceive ad­di­tion­al pay­ments and roy­al­ties on sales if the drug wins reg­u­la­to­ry ap­proval. Be­yond Bat­ten is rein­vest­ing its mon­ey to search for ad­di­tion­al treat­ments that could com­ple­ment the po­ten­tial ther­a­py.

“We’re not re­liant on bake sales,” Ben­son said.

By Jared Whit­lock

First pub­lished at KHN (Kaiser Health News) — a non­prof­it news ser­vice cov­er­ing health is­sues. It is an ed­i­to­ri­al­ly in­de­pen­dent pro­gram of KFF (Kaiser Fam­i­ly Foun­da­tion), which is not af­fil­i­at­ed with Kaiser Per­ma­nente.

The mRNA player Moderna is further cementing its presence on the African continent.

Moderna announced on Thursday that it has finalized an agreement with Kenya’s government to partner up and bring an mRNA manufacturing facility to the east African nation. The new facility aims to manufacture up to 500 million doses of vaccines annually. Moderna also said the new facility will have the ability to spike its production capabilities to respond to public health emergencies on the continent or globally.

ViiV Healthcare has teamed up with the UN-backed Medicines Patent Pool and three generic manufacturers to expand access to medicine that can prevent HIV.

ViiV and the Medicines Patent Pool jointly announced Thursday that the MPP signed sub-licensing agreements with Aurobindo, Cipla and Viatris to manufacture generics of a long-acting form of cabotegravir for HIV pre-exposure prophylaxis (PrEP). As a result of the agreement, the manufacturers will be able to develop, manufacture and supply generic versions of cabotegravir LA in 90 countries — subject to regulatory approvals.