Puma wins big FDA OK for ner­a­tinib af­ter run­ning the gamut with in­vestors

Short in­vestors loved to hate Puma Biotech­nol­o­gy, tak­ing the com­pa­ny $PBYI to task for the side ef­fects that ham­pered its lead can­cer drug ner­a­tinib. But the FDA had no trou­ble sanc­tion­ing the prod­uct for breast can­cer, ap­prov­ing it to­day for use in pre­vent­ing re­cur­rence of the dis­ease af­ter the biotech gained a lop­sided vote in its fa­vor among out­side agency ex­perts.

The FDA ap­proved ner­a­tinib — to be sold as Ner­l­ynx — for pre­vent­ing the re­turn of breast can­cer af­ter ther­a­py in­clud­ing trastuzum­ab. And the em­pha­sis in the OK was on adding op­tions for doc­tors and pa­tients.

“HER2-pos­i­tive breast can­cers are ag­gres­sive tu­mors and can spread to oth­er parts of the body, mak­ing ad­ju­vant ther­a­py an im­por­tant part of the treat­ment plan,” said Richard Paz­dur, M.D., di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence and act­ing di­rec­tor of the Of­fice of Hema­tol­ogy and On­col­o­gy Prod­ucts in the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search. “Now, these pa­tients have an op­tion af­ter ini­tial treat­ment that may help keep the can­cer from com­ing back.”

There are some caveats in the la­bel. Con­cerned about the high rate of Grade 2 and Grade 3 di­ar­rhea in the clin­i­cal stud­ies, reg­u­la­tors are telling physi­cians to stop us­ing the drug if their pa­tient ex­pe­ri­ences Grade 4 di­ar­rhea or Grade 2 af­ter a max­i­mum dose re­duc­tion. But Michael Schmidt at Leerink sees the plus­es as well in a broad la­bel:

The prod­uct la­bel looks broad, not re­strict­ing use to spe­cif­ic pa­tient pop­u­la­tions (e.g., hor­mone-re­cep­tor [HR] pos­i­tive pa­tients) and there is no black box warn­ing. The pre­scrib­ing in­for­ma­tion con­tains fair­ly de­tailed in­for­ma­tion about the use of an­tidiar­rheal pro­phy­lax­is mea­sures, pro­vid­ing spe­cif­ic in­for­ma­tion on how to man­age the drug’s main side ef­fect.

Puma says it isn’t re­leas­ing the price yet and has no time­line on that. Its stock price still had some up­side left af­ter the OK, though, with shares surg­ing 7.5% on a com­pa­ny with a $3.2 bil­lion mar­ket cap. Now that the ap­proval has come through, look for lots more chat­ter about Puma as a po­ten­tial takeover tar­get — even though M&A has large­ly been MIA this year in biotech.

Alan Auer­bach

The FDA ex­perts raised a va­ri­ety of con­cerns in their re­view of ner­a­tinib, mak­ing some points that could hin­der the drug’s mar­ket po­ten­tial now that Puma CEO Alan Auer­bach has a green light to sell it. Crit­i­cal to its suc­cess is a bet­ter un­der­stand­ing of its prop­er role in treat­ing breast can­cer, and the lim­its of its ef­fec­tive­ness.

To get here, Puma had to over­come reg­u­la­tors’ ob­jec­tions in the spring of 2016 to fil­ing the drug with the da­ta that were avail­able, cit­ing a prob­lem­at­ic ap­proach to de­ci­pher­ing the re­sults. The shorts were al­so fix­at­ed on a high rate of grade 3 di­ar­rhea in the tri­als, but ex­perts hard­ly paid any at­ten­tion to that, hap­py to trade off the po­ten­tial for man­age­able side ef­fects for a chance of adding a new ar­row to their quiver of ther­a­pies.

“There’s no ex­cla­ma­tion point af­ter my ‘yes’,” said An­drew Sei­d­man, an on­col­o­gist at Memo­r­i­al Sloan Ket­ter­ing af­ter the FDA vote. “It’s just a yes.” He added that he was hap­py that the drug looks durable and the sta­tis­ti­cal analy­ses ap­plied to the da­ta giv­en the sig­nif­i­cant changes to the study de­sign. “I do think that physi­cians will se­lect pa­tients very se­lec­tive­ly for us­ing this,” he not­ed, echo­ing a con­cern that the ap­proval the com­pa­ny was seek­ing was too broad giv­en the da­ta avail­able.

Puma’s po­si­tion has been height­ened af­ter an­a­lysts fa­vor­ably com­pared ner­a­tinib’s 34% re­duc­tion in the risk of re­cur­rence or death against a mar­gin­al im­prove­ment seen in a Roche com­bi­na­tion study of Per­je­ta and Her­ceptin. It takes a leap to do these kinds of cross-tri­al analy­ses that dri­ve drug de­vel­op­ers a tad crazy now and then, but Wall Street an­a­lysts were quick to give Puma a thumbs up, par­tic­u­lar­ly af­ter it had just hand­i­ly won the FDA pan­el vote.

Eval­u­atePhar­ma pegged 2022 sales at $1.25 bil­lion, mak­ing it one of the top 15 drugs in the in­dus­try pipeline at the be­gin­ning of this year.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. The idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.

Ver­tex deal for Scot­land — no deal for Eng­land

Cystic fibrosis (CF) drug maker Vertex Pharmaceuticals — which is still locked in negotiation with NHS England to endorse the use of its medicines — has successfully negotiated a deal with Scottish authorities.

A month ago, the Scottish Medicines Consortium spurned two of the company’s medicines — Orkambi and Symkevi — citing uncertainty over their long-term efficacy in relation to their cost.

Tony Kulesa, Brian Baynes. Petri

Star founders, in­ves­ti­ga­tors hud­dle around new Boston ac­cel­er­a­tor spot­light­ing young en­tre­pre­neurs

As a widely recognized biotech hub, Boston is undoubtedly one of the best places to start a new company at the frontier of biology and engineering. With a dense network of incubators, venture capitalists and talent, seasoned company founders can have their pick of partners and models launching their latest startups.

But for young, aspiring entrepreneurs, it’s a very different scene.

Big VC firms might hire you to work on their ideas instead of yours, and accelerators may not offer the kind of deep technical expertise and guidance needed to make it in the field.

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From part­ner to knight in shin­ing ar­mor: Cas­tle Creek to buy Fi­bro­cell

In April, Castle Creek swooped in to partner with the embattled gene and cell therapy Fibrocell to shepherd its lead gene therapy for a type of “butterfly” disease into late-stage development. Now, the New Jersey-based dermatology company is acquiring its partner in a deal worth $63.3 million.

Pennsylvania-based Fibrocell last year initiated a review of strategic alternatives, including a sale.