Tucatinib Receives FDA Approval

Little tucatinib is all grown up! The TKI that started out at Array long, long ago has now been FDA approved in combination with Herceptin and Xeloda for the treatment of 2L+ HER2+ metastatic breast cancer. Additional international approvals could be imminent, as the submission was part of a concurrent review program between the FDA and worldwide regulatory authorities. This is fantastic news for everyone but the Kadcyla sales force, though Genentech will get a slice of the pie via some incremental Xeloda sales.

The approval was supported by data from the HER2CLIMB trial, which enrolled 612 subjects and randomized them 2:1 to tucatinib or placebo plus Herceptin and Xeloda. Subjects with brain mets at baseline comprised 47.5% of the study population. This is their story:

Among subjects with measurable disease at baseline, the confirmed objective response 40.6% in the tucatinib group and 22.8% in the placebo group. But look at those numbers! The brain mets patients didn’t do much worse than patients with visceral mets. Cascadian went in boldly by enrolling brain mets patients, and the gamble paid off. They have brain mets featured prominently in their labeling, and they’re an example for all the companies that have excluded brain mets patients from their trials for fear of muting response rates. But patients in the real world, in HER2+ breast cancer, have brain mets. I have brain mets. I’ve looked at a lot of eligibility criteria, and while we’ve seen brain mets exclusions gradually relax over the past decade, most trials that allow them still caution that they must be stable.

Cheers to you, Cascadian/SeaGen.

Immunomedics’ P3 Halted for Efficacy

After a slow-enrolling trial, a failed acquisition, an FDA Complete Response Letter, years of unspecified manufacturing issues and about eleven different management teams, Immunomedics finally had some good news last week: their phase 3 ASCENT trial was halted for efficacy. Wait, not just efficacy, compelling efficacy. (That’s a new one for me.) And since Immunomedics’ leadership roles are rented, not owned, there was naturally a concurrent announcement that they’ve appointed a new CEO.

The 529 subjects enrolled in ASCENT were randomized 1:1 to receive either sacituzumab (a TROP-2-directed ADC with an irinotecan metabolite payload) or standard of care chemo. Patients had to have had at least two prior lines of therapy in the metastatic setting, including a taxane, so the single-agent chemo options allowed by the trial are not particularly exciting and set sacituzumab up well on the efficacy endpoints: eribulin, capecitabine, gemcitabine, or vinorelbine. The primary endpoint is PFS, with secondary endpoints including OS and duration of response.

I do think sacituzumab will be approved under its current accelerated designation, which means the full analyses will have to be delivered at some point. A full approval could still be a year out, but I don’t think that’s the only reason behind what I expect to be a lack of fanfare come PDUFA day in June. This drug just isn’t going to be a blockbuster. It addresses a small market (TNBC patients number about 10-15% of the breast cancer population), and this “targeted” therapy brings with it some heinous toxicities that remind us it’s closer to a chemo reformulation than a Kadcyla, which I know has lost its luster but really felt like a game-changer circa 2010. And while a Kadcyla comparison isn’t apples-to-apples, as it’s HER2+ targeted and addresses a larger, likely healthier market, we’ll reference it here because, practically, there aren’t that many other ADCs kicking around to reference.

One of the benefits of ADCs is you take a supremely toxic payload and, by targeting it to a protein, minimize the adverse events and make the drug tolerable. Kadcyla did this with maytansine, which is a tubulin binder with side effects too severe to be clinically useful. Link it to Herceptin, and poof! Problem solved.

Even with the TROP-2 “targeting”, which I’ve always found suspect given the high reported AE rates (TROP-2 is thought to be expressed in many solid tumors but only minimally in normal tissue – so is the issue the antibody or the linker?), sacituzumab is a difficult drug to tolerate. In the phase 1/2 study, 41% of subjects experienced adverse events of grade 3 or higher, with 39% experiencing grade 3 or higher neutropenia. It did knock diarrhea, which is the biggest issue with irinotecan, down to 59% overall and 13% grade 3 or higher, which is … better. On the less deadly side, about half of patients lost their hair. Targeted, you say? EMILIA, Kadcyla’s P3, demonstrated a serious adverse event rate of 18%. That’s what an ADC can do. That’s how you improve quality, not just quantity, of life. Anyone can go on, and likely stay on, Kadcyla with a minimum of surveillance and intervention, though, in general, HER2+ patients are easier to manage and are more likely to be healthier at baseline. That’s what TNBC needs and what immunotherapy is trying to deliver, however modest the results have been so far. There are a lot of drugs out there, so when do we get quality and not just “options”?

In fairness, sacituzumab rates as an option. Immunomedics has been parading the early efficacy data around for so long that I nearly have it memorized: it’s about a 30% response rate and 6 months of PFS, right? That kind of response rate is good in TNBC; I’d expect standard of care to be 15-20%, worse as you move further away from first-line treatment, and PFS to be closer to 4 months. As for how that predicts the outcome of the study and the FDA decision, the AEs will be worse in the treatment group, but it’s going to get approved. The question is what kind of market is waiting for it. We haven’t seen much excitement from anyone not on Immunomedics’ payroll, but we know that at least as of 2017, Seattle Genetics was … less than enthused with their antics. I’m with Seattle. TNBC is a truly underserved population that needs better, but this drug has real limits.

DS-8201 has a PDUFA Date

Yes! The date is F1Q:20, so I might be getting a prolonged OS for Christmas!

Daiichi announced today that they’ve been granted FDA Priority Review for their highly worthy DS-8201, which looked promising out of the gate and recently demonstrated a 59.5% response rate in HER2+ metastatic breast cancer patients who had previously been treated with T-DM1. Those results, from a 118-subject Phase 1, were published in June. The study also reported some total insanity, like a 20.7-month duration of response (DOR) and a 22.1-month PFS. It’s not comparable given the phases, designs and number of subjects enrolled in this phase 1 versus EMILIA, but T-DM1 had a phase III PFS of around 9-10 months, so DS-8201 is likely to displace that agent as the second-line treatment of choice in this setting (first-line being taxane + Herceptin + Perjeta).

The data above are old news, but the press release says the submission package also includes pivotal phase 2 DESTINY-Breast01 data, which “validated” the phase 1 results and which no one has seen yet, though they note that it will be presented at San Antonio. DESTINY 1 looks at a similar population (T-DM1 pre-treated MBC), but its 230 subjects were randomized to varying dose levels. Primary endpoint is ORR, so it would be shocking if this result isn’t pretty compelling, considering what we’ve seen so far.

Like T-DM1, DS-8201 is an ADC where Herceptin is conjugated to a chemo agent; in DS-8201’s case, it’s a TOP-I inhibitor, similar to irinotecan.

Puma Hobbling Along a Year After Neratinib’s Launch

The Nerlynx needs your help. On their 3Q earnings call, Puma Biotech presented brutal sequential sales for neratinib, tanking the stock, hopes & dreams, etc.

In millions.

That’s a 3.5% increase from 2Q18 to 3Q18.

This is not the story for, say, Perjeta, which was initially launched in the small market of first-line HER2+ metastatic breast. A year out from its introduction, in an equivalent period as referenced above, sales increased 34.5% over the previous quarter. Six years later, after having picked up approvals in the adjuvant and neoadjuvant settings, Roche reported Perjeta sales of CHF 2.0 billion ($2.0 billion) for the first nine months of 2018, which is a 24% increase year-over-year. Kadcyla, another HER2+ drug which is still only approved for use in metastatic patients, grew 30.8% between its fourth and fifth quarters on the market and has booked CHF 728.0 ($743.3 million) in sales so far this year, an 8% increase over the prior-year period. Deviating from HER2 for a minute, Ibrance was launched in first-line, HR+ breast and was growing 36.2% a year from launch, only to report nearly $3 billion in sales in the first nine months of 2018, even as U.S. sales are being impacted by increased competition.

This is just an illustration of the growth trajectory that can be expected with a new breast cancer drug managed correctly. Puma’s performance is not normal. They continue to promise that Europe will deliver revenues, but there was one tidbit in the earnings call transcript that I missed before: their proposed label in the EU market is ER+, HER2+ patients, while in the U.S. it’s all HER2+ patients (about 20-25% of the 260k new U.S. breast cancer diagnoses each year). I checked the APHINITY demographics and was surprised to find the ER+/HER2+ cohort was as big as it was – about 64% of patients in that study (compared to 57% in Puma’s own EXTENET) – but they’re still losing a big chunk of the market. Whether the drug will get any traction in the conservative EU market is a different issue, but when Americans are skeptical, what does that tell you?

Still no news on NALA in the metastatic setting, aside from reiterating that it’s going to be 4Q this year or the first half of next year. No urgency, it seems, though at this rate Kadcyla could be approved in the neoadjuvant setting before we even see NALA, further eating away at the utility of neratinib. For an anecdotal example of what Puma’s extended adjuvant delusion is costing them, my own doctor had a HER2+ metastatic patient with decent systemic control and progressive brain mets. Whatever I think of Puma management, we have one drug in breast cancer that passes the blood-brain barrier. Tucatinib is coming, but at the moment, if you’ve failed Tykerb, neratinib is the only marketed option. My doctor was worried insurance wouldn’t pay for it because of the early-stage label. I said of course they would. It’s in the guidelines.

She had no idea what I was talking about. I pulled up the press release about neratinib being added to the HER2+ CNS guidelines on my phone. I only knew about this because I stalk the company. An actual doctor who needs the drug available had no clue. This is how Puma thinks things should be done. Insurance apparently said yes to the neratinib request on the first go, and the patient is on it now, so you’re welcome, guys.

The unmanageable diarrhea came up on the earnings call, as it always does, and the keyword remains compliance. Puma assured investors that the specialty pharmacies are sufficiently hounding patients to refill, that they’re offering vouchers for loperamide, and that they’re working to get budesonide and colestipol prophylaxis added to the label (so many drugs for these patients!). What is the rationale? The patient is waffling on refilling their prescription, because, you know, there’s nothing wrong with them, and it’s the free Imodium that persuades her? Like the free hat when you sign up for the low-rent gym in the shopping center parking lot? I can’t think of another management team so out of touch with their own market. How many Puma staff and affiliates are charged with pressuring healthy patients to take unnecessary meds versus reaching the prescribers and patients who could actually benefit from neratinib – and have every motivation to take the drug as prescribed, with the hope of refilling all the way through improved OS?

Alpelisib Summits Mt. PI3K

ESMO was a snooze, right? No new drugs out of nowhere, no hotly-anticipated studies knocking it out of the park (cough, IMpassion, cough). Which I guess frees us up to talk about alpelisib.

Novartis announced results from their SOLAR-1 study, which succeeded where buparlisib (also NVS) and taselisib (Roche) failed. In patients with PI3K-mutated, hormone-positive and HER2-negative advanced breast cancer, alpelisib plus fulvestrant achieved a PFS of 11 months, compared to 5.7 months for fulvestrant alone, and an ORR of 36% for alpelisib + fulvestrant, which compares to 16% in fulvestrant alone. These are hormone-positive patients, so we won’t have OS data for another few decades, but these are good numbers. It wasn’t Ibrance/letrozole, which blew out a wild PFS in the first-line setting (notably, the SOLAR-1 patients will have progressed on an AI as well as possibly a CDK 4/6 inhibitor), but it’s good, and the first real validation we’ve seen of PI3K targeting in breast.

This would have been a perfect announcement if not for the AEs. Hyperglycemia was reported for 64% of alpelisib patients (compared to 10% among controls); in 37%, hyperglycemia was grade 3/4. Grade 3 hyperglycemia is defined as blood sugar of 250-500 mg/dL; grade 4 is >500 mg/dL. Which sounds challenging, even in patients who theoretically have bigger problems. These are patients that are poised to live a really long time with a good quality of life. Is any onc out in the community, dealing with real patients, psyched about managing blood sugar of 400? The press release didn’t break out the rate of dose reductions, but what does that inevitability do to efficacy?

To their credit, Novartis has been fairly relaxed about enrolling diabetics in its PI3K studies. SOLAR-1 excluded type 1, but allowed controlled type 2; BELLE-2 and BELLE-3, the buparlisib studies in HR+ MBC, didn’t appear to restrict based on diabetes or blood glucose, though other, investigator-led studies did. SANDPIPER, the P3 taselisib, excluded Type 1 or Type 2 diabetes requiring anti-hyperglycemic medications. Still, not everyone is going to be represented in the SOLAR-1 population, and there’s a reasonable likelihood that physicians will be prescribing for patients with high baseline blood glucose or less well-controlled diabetes. (And while there’s an argument that metformin and PI3K/AKT/mTOR inhibitors are synergistic, and that by adding metformin to one of these drugs you’d get both protection against a blood sugar crisis and enhanced anti-cancer efficacy, there’s at least some evidence with everolimus that it’s not so straightforward. Though these diabetic neuroendocrine patients who were on metformin when starting evero did better than their non-diabetic counterparts.)

Everolimus is an older, HR+ breast-approved mTOR inhibitor that popped up in a couple of ESMO abstracts (here and here) that aren’t really interesting enough to discuss on their own but that roughly echoed what we know from BOLERO-2, which is that evero doesn’t really care about PI3K positivity. This is notable since this drug for patients with targetable, frequently-mutated PI3K has been one of the prime examples of precision medicine in practice. It’s been offered to me a couple of times based on genomic sequencing (never in a large center, obvs), which I always declined because I was waiting for one of the next-gen PI3Ks. Taselisib turned out to be a disaster, despite the all the strategizing that preceded signing that consent. I think this is a good example of the kind of hold that sequencing has over patients; those mutations feel a lot like capital, and I put a huge amount of effort into deciding when and how to cash it in. Diabetes aside, if alpelisib works, and exclusively in PI3K-mutated patients (there is PI3K-wild-type cohort in SOLAR-1 being tracked for a secondary endpoint), it could help reverse what has felt like a big disappointment in personalized medicine.

Checking in on Breast ADCs

With Mersana struggling to dig its way out of the pain of a clinical hold, it seemed like a good time to check in on the many antibody-drug conjugates (ADCs) in development in metastatic breast cancer. T-DM1 made it look so easy.

	Sponsor	Target	Payload	Status
T-DM1	Genentech	HER2	DM1 (maytansinoid)	Approved
Sacituzumab govitecan (IMMU-132)	Immunomedics	TROP2*	SN-38 (irinotecan metabolite)	Phase 3
Trastuzumab deruxtecan (DS-8201a)	Daiichi Sankyo	HER2	Exatecan derivative	Phase 3
SYD985	Synthon	HER2	Duocarmycin	Phase 3
XMT-1522	Mersana	HER2	AF-HPA (auristatin)	Phase 1b
Ladiratuzumab vedotin (SGN-LIV1A)	Seattle Genetics	LIV-1*	MMAE (auristatin)	Phase 1
ARX788	Ambrx	HER2	MMAF (auristatin)	Phase 1
Glembatumumab vedotin	Celldex	GPNMB	MMAE (auristatin)	Discontinued at P2b (METRIC)

Development-stage drugs bookended with T-DM1 and Celldex, since they’re referenced in this blog; asterisk if Sponsor claims you don’t need confirmed expression of the marker to benefit from the drug.

Mersana was put under a partial clinical hold in July when a patient died on-study. The hold was lifted two months later with some protocol changes – “increased monitoring”, more limitations on hepatic function for future subjects and a new dosing schedule, with the drug being administered every four weeks instead of every three. The ClinicalTrials.gov status is still active, not recruiting, and they haven’t updated the enrollment criteria or dosing schedule yet. So, as the stock will attest, we’ve heard nothing good about XMT-1522 so far, only bad, but I’m not totally horrified by the safety signal this early. Mostly because this is a heterogenous population in something of a baby basket trial. They’re enrolling the traditional HER2+ MBC cohort, which is, generally, a pretty healthy bunch – but they’ve also got HER2-low MBC, HER2+ gastric and HER2 mutated or overexpressed NSCLC cohorts. The mix as of June was 18 breast patients (HER2 status unspecified), 3 gastric patients (again, no HER2 detail) and 1 HER2-amplified gallbladder patient. There’s some unpredictability there, and likely variation in clinical status.

Would I enroll? No way. The drug is too weird. I don’t want a “novel HER2 antibody”. Mersana says their antibody attaches to a different HER2 epitope than Herceptin and Perjeta; that’s about all we know about it. They’ve also developed a novel binding technique and aren’t using a traditional linker. Too many variables, guys. If you want patients to enroll in a phase 1, at least make them feel like they’re getting some Herceptin. Daiichi and Synthon have an antibody that is virtually identical to trastuzumab, and that strikes me as exactly right; leave the uncertainty to the linker. For what it’s worth, trastuzumab is believed to contribute to the efficacy of T-DM1 – not just due to efficient binding, but by exerting some immune-mediating effects. I’ll take it. Why get creative? We don’t need a more perfect antibody. The benefit is in the payload.

Synthon has been so quiet about their trastuzumab-duocarmycin (alkylating agent) ADC that I was surprised to find that it opened a P3 a year ago in HER2+ MBC, adorably called TULIP. They’re from the Netherlands. They had an ASCO abstract. Preliminary ORR of 33%, and no one died. Their eyes got a little runny. Cool. Sounds good.

Daiichi has been so busy with DS-8201a lately that they probably deserve a separate post (spoiler: am pumped for this drug), and we’ll skip over Ambrx, which no one knows anything about. That brings us to the ADCs that target, well, something. Maybe cancer.

Seattle Genetics is developing what used to be called SGN-LIV1a, which purportedly targets LIV-1. What’s intriguing about this is the evolution of the study design on their P1, which has been open since the Year of Our Lord 2013. It’s progressed from a dose escalation in 50 subjects where positive LIV-1 expression on a new biopsy was required for enrollment to a 300-subject, multi-cohort free-for-all where a new biopsy is required for enrollment. The new biopsy thing kills me; where do sponsors get the audacity to require this? Despite making it a condition of enrollment, they don’t have to pay for it, as it can easily be billed as routine care. More importantly, it’s risky for many patients. Especially considering the risk/reward on P1s: if I can die from unexplored toxicity, you don’t get an invasive fresh biopsy. At any rate, SeaGen has now changed course to say that LIV-1 is expressed almost universally in metastatic breast cancer and reported some early results (25% ORR in a TNBC cohort of 60 subjects). I’m not sure the early responses will stand given Celldex, which also had an MMAE payload; whether the LIV-1 target is viable or not, these patients will have progressed on at least one tubulin binder and likely a couple. Let’s keep expectations low on this one, though they did beat IMMU on opening a first-line TNBC ADC + checkpoint inhibitor study (SGN-LIV1a + pembro) and got into the MORPHEUS study, so they’re definitely part of the conversation.

Immunomedics continues to be irritating. They are relentless in their promotion of their TNBC unicorn that has an SN-38 payload that’s – what is it? – four billion times as potent as irinotecan? Does that mean the patients will survive four billion times as long? IMMU has years of follow-up on these subjects by now, but we’ve only been fed the same tiny nibbles of data over and over; as a reminder, it was a 30% response rate on a cohort of MGH dream patients. This won’t hold up in phase 3, but IMMU got FDA to accept their BLA on Glitter Unicorn-umab on P1/2 data, with a PDUFA date set for January. It’s hard to call whether they’ll get approved or be forced to wait for the P3, but if they do get approved, here’s hoping they go away for a while. With weak data, IMMU should be pretty well trapped in the third-line setting, and we can let more interesting agents (and study designs) sort out earlier lines of TNBC treatment.

With all this activity and so many viable drug candidates, I’m wondering if investors aren’t being more forgiving of Mersana in part because we don’t really need them. We have some near-term approvals coming that will significantly increase the number of ADCs on the market, but the big change since T-DM1 in 2013 is that we’re now fully committed to combination therapy. Targeted drugs with manageable toxicity profiles are making creative cocktails possible, and the results are a lot more compelling than what we’re seeing in the box-checking monotherapy trials that get these agents approved. For instance, T-DM1 performs well on its own, but we’ve already been teased with a 60% response rate when you pair the drug with neratinib. It’s never been easy to enroll a phase 1, but when the sky’s the limit on combos where there’s already some comfort and clinical experience, the competition for patients and investigators is going to intensify.

I Tried It: Taselisib

Update: the morning after I posted, investigators presented SANDPIPER data in an MBC session. In response to modest benefit and AE concerns, Roche announced that they would not be pursuing an FDA submission.

Spoiler alert: check out this table presented today at ASCO.

I enrolled in a study combining taselisib with HER2-targeted therapy (T-DM1 or HP, with prior therapy on either option allowed) in metastatic breast cancer. Worth noting: PI3K mutations were not required for enrollment, in line with Genentech’s overall all-comers strategy (e.g., non-targeted atezo). My experience was not apples-to-apples with the MATCH patients, who were enrolled solely on the basis of a PI3K mutation, regardless of tumor origin. But I think it’s analagous, given that I only enrolled because of my PI3K mutation. In 2012 I had a Caris test, which was then much more exciting than it is now; so exciting that I wasn’t even mad that they depleted a five-centimeter block of tumor doing a panel of about a dozen genes plus chemosensitivity testing. We’ve come a long way in six years. Among the results was a PI3K mutation. The wonderful Dr. Cristofanilli, whose enthusiasm for targeted therapies and novel diagnostics is truly inspiring (whether he’s entirely right about their clinical relevance, it’s contagious), told me five years ago to try Afinitor in combination with Herceptin and vinorelbine. Afinitor targets mTOR, which shares a pathway with PI3K and is approved for use in hormone-positive breast cancer, in combination with Aromasin, among other indications. He recommended it over a T-DM1 trial, because he predicted, accurately, that in the near future it would be no problem to get T-DM1, though at the time it seemed like the drug would never make it to market; payer uncertainty with the off-label Afinitor was another issue (BOLERO-3 was published a couple of years later, and I imagine this would make reimbursement less of a wildcard, assuming the prescriber was willing to push for it). While I was touched that after one appointment, he would’ve gone to bat with my insurer, I went with the T-DM1 trial. There were so many next-gen PI3K inhibitors in development, and I had my eye on BKM120.

I waited. And waited. Development was apparently discontinued sometime late last year. If you look at Novartis’ 2017 annual report, BKM120 is suddenly absent from the pipeline. This was not entirely surprising, to the extent that I didn’t even see it reported anywhere, given the AEs; PI3K inhibitors are known to cause neuro issues, and the poor ER+ study subjects with their indolent cancers were up and trying to kill themselves on trial. There were also efficacy concerns. BYL719 still has a heartbeat, but I haven’t heard much about it. They’re trying it with letrozole in HR+ breast, and it seems fine.

Anyway, this story is about taselisib. I enrolled, and I lasted one week. The nausea was terrible, terrible, ondansetron every eight hours terrible, which I usually avoid because I’m so scared that if I take it, I’ll build up some kind of anti-emetic tolerance and this drug that is considered magic and the best choice we have against nausea will no longer work for me. My usual strategy against nausea is to eat candied ginger (it’s stocked with all the nuts in Whole Foods) and to lie absolutely still, which is reasonably effective. Plus my skin progressed, after a few years of relative stability, and I panicked. It just went crazy.

ME: I feel like I did something mutagenic. That maybe the PI3K was there, but it wasn’t driving anything, and now I’ve woken it up.

DOCTOR: Yeah, that’s legitimate.

He’s the best because he tells me the truth.

Like 100% of the MATCHed patients referenced above, I was not a responder. There seems be some suspicion of the drug among physicians; my husband came home recently and said someone asked him, re: taselisib, “Does that thing even work?”

Well. We’ve associated the efficacy of drugs targeting the mTOR pathway with hormone-positive breast because that population is pretty overwhelmingly PI3K-mutated (it may be as high as 50%). But if you look at MATCH, the mutation doesn’t really explain it. For me personally, this also isn’t the first time I’ve targeted the mTOR pathway; I’ve taken metformin since diagnosis, and if that has any anti-cancer activity, it’s along this pathway, and I definitely haven’t associated it with rapid PD.

I haven’t written about my taselisib experience because I really don’t know what to make of it; it’s disappointing, and I don’t want this blog to be a series of lame anecdotes, because oncology is a thrill to me in ways that are separate from my own case. While I want to be honest about what happens to me, it’s a lens and not the thing itself. So when I see that I join the 0% of MATCH patients who were PI3K mutated and yet taselisib non-responders, there is some relief that I’m not going to be the one to be a black mark on this drug (I did ask my doctor if I would be on the record as non-evaluable, because I progressed halfway through the first cycle, or as a PD, and I don’t actually know what happened), but I also want us to believe in genomics until something better comes along. Maybe PI3K is just not an ALK, or, in ASCO 2018 terms, a RET. It’s not like chemo works so great. We can do better than that, right?

EXEL’s trash, Kadmon’s treasure? 10+ years with tesevatinib

Three years ago, I learned of KD-019, an EGFR-inhibiting wonder TKI for which there just happened be a study enrolling, right at the mid-tier academic institution/portal to hell in which I was currently sitting. I nodded along appreciatively to phrases like better than Tykerb! while thinking, Kadmon. Kadmon. Oh, right, the one where the CEO just got out of prison.

Continue reading “EXEL’s trash, Kadmon’s treasure? 10+ years with tesevatinib” →

Puma Post-APHINITY

Puma presented at Cowen today, and I listened to the webcast hoping for a reaction to APHINITY, but alas, they kept Q&A to the breakout session. The tone of the presentation did seem a little grim, but between the crushing of adjuvant dreams and half the slides being devoted to unmanageable diarrhea, I guess it was always going to play grim. Continue reading “Puma Post-APHINITY” →

Seattle Genetics Bags Irinotec- Er, IMMU-132

Two billion dollars seems spendy for a repackaged chemo agent that has been on the market since 1996. It’s no secret, either; irinotecan is standard of care in colon and lung, though, weirdly, it doesn’t get prescribed a lot in breast (despite the fact that irinotecan targets TOP-1, which is commonly overexpressed in breast).

What Seattle Genetics may be banking on is the branding; this is a “new drug” for triple negative breast cancer, which is great marketing when, in reality, there is no drug that is for TNBC. Continue reading “Seattle Genetics Bags Irinotec- Er, IMMU-132” →