Phar­ma­co­ge­net­ics: FDA re­leas­es ta­ble of gene-drug in­ter­ac­tions

The FDA on Thurs­day pub­lished a ta­ble iden­ti­fy­ing more than 50 gene-drug in­ter­ac­tions that the agency says are sup­port­ed by sci­en­tif­ic ev­i­dence and an­nounced it is con­sid­er­ing new ap­proach­es to eval­u­at­ing phar­ma­co­ge­net­ic as­so­ci­a­tions.

“Con­sis­tent with our mis­sion to pro­tect and pro­mote pub­lic health, we be­lieve it is im­por­tant to take steps now to help en­sure that claims be­ing made for phar­ma­co­ge­net­ic tests of­fered to­day are ground­ed in sound sci­ence to avoid in­ap­pro­pri­ate man­age­ment of pa­tients’ med­ica­tions,” said Cen­ter for De­vices and Ra­di­o­log­i­cal Health Di­rec­tor Jeff Shuren and Cen­ter for Drug Eval­u­a­tion and Re­search Di­rec­tor Janet Wood­cock.

Back­ground

The re­lease of the ta­ble comes af­ter years of grap­pling over how the FDA should ap­proach phar­ma­co­ge­net­ic (PGx) test­ing and the broad­er field of lab­o­ra­to­ry de­vel­oped tests (LDTs). In 2018, the FDA is­sued a safe­ty com­mu­ni­ca­tion and state­ment ad­vis­ing that many ge­net­ic tests pur­port­ing to pre­dict a pa­tient’s re­sponse to med­ica­tions have not been re­viewed by the agency and may not be sup­port­ed by sci­en­tif­ic or clin­i­cal ev­i­dence.

At the same time, var­i­ous in­dus­try groups, in­clud­ing the Amer­i­can Clin­i­cal Lab­o­ra­to­ry As­so­ci­a­tion (ACLA) and the Coali­tion to Pre­serve Ac­cess to Phar­ma­coge­nomics In­for­ma­tion, have pushed back against the FDA’s ef­forts to crack down on phar­ma­co­ge­net­ics tests.

In a cit­i­zen pe­ti­tion filed last month on be­half of the Coali­tion to Pre­serve Ac­cess to Phar­ma­coge­nomics In­for­ma­tion, law firm Hy­man, Phelps & Mc­Na­ma­ra called on the FDA to re­vise its safe­ty com­mu­ni­ca­tion to state that test mak­ers “may com­mu­ni­cate in­for­ma­tion about gene-drug in­ter­ac­tions as part of ge­net­ic test re­ports to the ex­tent that such in­for­ma­tion is sup­port­ed by ad­e­quate ev­i­dence and is not con­traindi­cat­ed by in­for­ma­tion in drug la­bels.”

Phar­ma­co­ge­net­ics As­so­ci­a­tions Table

The FDA says the ta­ble is “in­tend­ed to pro­vide the agency’s view of the state of the cur­rent sci­ence in phar­ma­co­ge­net­ics” and in­cludes es­tab­lished gene-drug in­ter­ac­tions that ap­pear in la­bel­ing and some in­ter­ac­tions that, while not ap­pear­ing in la­bel­ing, are sup­port­ed by suf­fi­cient sci­en­tif­ic ev­i­dence.

The ta­ble al­so de­notes phar­ma­co­ge­net­ic as­so­ci­a­tions that may in­di­cate an im­pact on a drug’s safe­ty or a pa­tient’s re­sponse and gene-drug as­so­ci­a­tions for which an im­pact has not been es­tab­lished.

The FDA stress­es that the ta­ble is not com­plete and that it will con­tin­ue to re­view sci­en­tif­ic ev­i­dence, in­clud­ing guide­lines de­vel­oped by the Clin­i­cal Phar­ma­co­ge­net­ics Im­ple­men­ta­tion Con­sor­tium, to ex­pand the list. The agency has al­so opened a pub­lic dock­et to so­lic­it com­ments from stake­hold­ers on spe­cif­ic phar­ma­co­ge­net­ic as­so­ci­a­tions that should or should not be con­sid­ered for the ta­ble.

The ta­ble comes with a host of dis­claimers, in­clud­ing that, “Each pa­tient’s ge­net­ic make­up is on­ly one of many fac­tors that may im­pact drug con­cen­tra­tions and re­sponse,” and that the FDA does not nec­es­sar­i­ly en­dorse phar­ma­co­ge­net­ic tests for in­ter­ac­tions in­clud­ed on the list.

The FDA al­so says the ta­ble “is not in­tend­ed to af­fect cur­rent reg­u­la­to­ry re­quire­ments or poli­cies, in­clud­ing the FDA’s pol­i­cy re­gard­ing com­pan­ion di­ag­nos­tics. Nor is the ta­ble in­tend­ed to make an as­sess­ment on the safe and ef­fec­tive use of, or reg­u­la­to­ry re­quire­ments for, tests that de­tect vari­ants in the ref­er­enced genes, or to pro­vide com­pre­hen­sive in­for­ma­tion on the de­scribed gene-drug in­ter­ac­tions.”

De­spite those dis­claimers, the list could of­fer in­sight to phar­ma­co­ge­net­ic test mak­ers on what the agency con­sid­ers suf­fi­cient ev­i­dence to sup­port spe­cif­ic phar­ma­co­ge­net­ic as­so­ci­a­tions.


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Ex-My­lan em­ploy­ee pleads guilty to in­sid­er trad­ing, il­le­gal­ly deal­ing on FDA ap­provals, earn­ings and Up­john merg­er

A former Mylan IT executive pleaded guilty Friday to an insider trading scheme where he bought and sold stock options on another executive’s advice.

Prosecutors secured the plea from Dayakar Mallu, Mylan’s former VP of global operations information technology, after uncovering the plan. Mallu collaborated with an unnamed “senior manager,” the SEC said, to trade options ahead of Mylan public announcements regarding FDA approvals, revenue reports and its merger with the Pfizer generics subsidiary Upjohn. The two subsequently shared profits.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Den­mark's Gubra to col­lab­o­rate with Bay­er on pep­tides; Sam­sung and Bio­gen re­ceive FDA ap­proval for Lu­cen­tis biosim­i­lar

Danish biotech Gubra announced a research collaboration and license agreement with Bayer to develop peptide therapeutics to treat cardiorenal diseases. The collaboration will utilize Gubra’s peptide drug discovery platform to identify potential candidates.

This is not the first time Gubra has partnered with a company on peptide therapeutics — they partnered with Boehringer Ingelheim back in 2017 to create peptide therapeutics to treat obesity.

Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.