Replies to post #2284 on Spectrum Pharmaceutecals Inc (SPPI)

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Continuation of comments on short article.

Hi Kojak, I am responding as a reply to post 2284 so the responses are linked and easy to find.

If afatinib does what he claims it does why does he use a reference (http://ascopubs.org/doi/10.1200/JCO.2012.45.6095) from June 2013 to justify his claim. No new data? Why? Maybe because it's not worth generating? He also claims afatibib is more potent in pre-clinical HER2 models but when the WCLC abstracts came out that afternoon there was another non-MD Anderson abstract (see post 2282) that stated

Conclusion
Poziotinib showed the most potent activity against HER2 exon 20 mutations. We also found that secondary C805S HER2 mutation was the common mechanism of acquired resistance, which most likely inhibit covalent binding of poziotinib with HER2.

The MDA abstract shot up his theory questioning the clinical effectiveness of pozi in HER2 ex20in and this second abstract did the same in a pre-clinical environment. Too funny. Another claim he made is that pozi will have a high bar in 1st-line because it will compete against trastuzumab. Granted the link he gave was a good one since it was about HER2 ex30in in NSCLC but the data consisted of ~47% of the patients in first-line therapy.

outcome with HER2-targeted drugs
Thirty-six patients did not receive any anti-HER2 drugs, whereas 65 (64.4%) patients received at least one HER2-targeted drug, of which 47 received one line, 14 patients two lines, and 4 patients more than two lines of anti-HER2 drugs. Overall, 88 targeted treatments against HER2 were given and evaluated, including trastuzumab (n = 57), trastuzumab emtansine (T-DM1, n = 1), neratinib (n = 14), afatinib (n = 11), and lapatinib (n = 5). RR, disease control rate (DCR), and PFS were 50%, 75%, and 5.1 months, respectively, for trastuzumab in combination with chemotherapy. Chemotherapy included vinorelbine (n = 24), docetaxel (n = 12), paclitaxel (n = 12), cisplatin (n = 7), whereas two patients had trastuzumab alone. PFS and OS for patients treated with trastuzumab-based combination are shown in Figure 2. RR, DCR, and PFS were 18.2%, 63.7%, and 3.9 months, respectively, for afatinib. Patients receiving neratinib were included in a clinical trial (PUMA-NER). Preliminary results have been reported [5], and the final results are awaited. Lapatinib was prescribed to five patients in third- or fourth-line; all five patients had PD when the first response assessment was made. One patient had a rapid response to T-DM1, as reported elsewhere [11]. Putting together the results of trastuzumab-based treatment and T-DM1, we observed an RR of 50.9% and a PFS of 4.8 months (95% CI: 3.4; 6.5).

And as we found out from the abstract, posi limited data beat those #s

Furthermore, 13 patients were enrolled in the HER2 cohort. Observed toxicities were similar to the EGFR cohort except one case of grade 5 pneumonitis, assessed to be possibly drug related. Twelve patients were evaluated for response with an ORR of 50% (95% CI 21.1-78.9) at eight weeks and a DCR of 83%.

This data is early but still a good sign. Next week we’ll get further clarification with 4 plus more months of data will be added to that.

The last point I have to make is that the proof of the pudding also came after the short article was released, actually yesterday. And that is that Spectrum’s P2 trial was updated with the first-line cohorts. As JT said this is a registrational trial. They are just giving pozi and nothing else. If there was an existing standard of care out there such as trastuzumab or afatinib, pozi would have to be randomized against them but that is not the case. That says a lot. All IMHO.

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Continuing evidence discrediting Sept's short article pozi pricing. Pfizer Xalkori follow-up Lorbrena for ALT mutations was just approved

to treat ALK-positive NSCLC after Xalkori and at least one other ALK inhibitor have failed, or as a second-line-treatment after Roche’s Alecensa or Novartis’ Zykadia.

Continuing from an article from Fierce Pharma

Xalkori is now vying in the previously untreated ALK-positive market with both Alecensa—which topped it in a head-to-head trial—and Zykadia. And soon, Takeda’s Alunbrig, which already boasts a second-line nod, could make its front-line debut; it posted positive data in untreated patients this July, following up with a big Xalkori head-to-head win in September. And Xalkori’s sales have retreated in response. In the first half of this year, its top-line contribution declined to $290 million from $296 million year over year.

It's being priced at $16,055 per month (i.e. $193,000 per year) amongst all this competition. Note that pozi won't have any competition and most likely will be priced higher. So when the short article by a Bob Shurma came out stating a $66,000 per yr price comparable to afatinib I had to laugh. But one needs to points these lies out or at least a severe lack of Due Diligence. A week later the $66,000 per year price was mentioned in an article by Avisol Capital Partners of which I just posted the Lorbrena pricing so they are aware you can't use an afatinib price of 5 yrs or so ago that was second TKI in that space at that time.

Edit - looks like it won't let me post a comment to the Avisol article. At least I got my original post published.