Astellas gets safety win for phase 3 menopause drug, setting up US, EU filings

 Astellas Pharma has shown its menopause medicine is safe, teeing up regulatory filings in the U.S. and EU—but analysts aren’t sure whether fezolinetant will find a market once approved. 

The Japanese pharma reported said the study has met its primary objectives including safety and tolerability and improvements in endometrial health at week 52. The most common adverse events were headache and COVID-19, which matched the placebo arm. 

The topline results come from the phase 3 trial called Skylight 4, which examined the long-term safety of non-hormonal menopause treatment fezolinetant. The study featured 1,800 women with moderate-to-severe vasomotor symptoms of menopause such as hot flashes and night sweats.

The readout will be used to inform future regulatory filings in the U.S. and EU, Astellas said. Also included in the future data package will be results from two other late-stage pivotal trials, Skylight 1 and Skylight 2, the latter of which previously found that fezolinetant reduced the frequency and severity of menopause symptoms.

Fezolinetant could have a huge market potential of up to $2.3 billion, according to Jefferies. However, the firm pointed to the disappointing performance of Pfizer-Myovant's MyFembree, which was approved in May 2021 for uterine fibroids, which makes them “worry about the commercial potential of women's health products generally.” Myovant reported sales of $2.4 million for MyFembree for the fiscal third quarter of 2021 in January. 

What could be dogging MyFembree is a significant out-of-pocket cost, which Jefferies placed at several hundred dollars, for many U.S. women. This is a hindrance for the med because fibroids can be controlled, albeit less effectively, with inexpensive generic drugs. Hot flashes are, however, much more common than uterine fibroids, but also less serious, the firm noted. 

Jefferies predicted that Astellas’ shares may “struggle after the event,” as investors had been waiting for the safety data. The company closed the day on the Japanese market up 13% to ¥1,845 ($16). 

https://www.fiercebiotech.com/biotech/astellas-gets-safety-win-menopause-late-stage-trial-setting-regulatory-filings

Gilead’s Tropics readout makes investors sweat

 When a trial is upsized, has its primary endpoint changed, and sees its readout delayed the chances are that things are not going well. Gilead investors were reminded of this today when the company’s long-awaited Tropics-02 study of Trodelvy was essentially confirmed as a damp squib.

Technically, of course, the topline result is positive, with a short statement from Gilead saying Tropics-02 had met its primary endpoint with a statistically significant improvement in progression-free survival. Much more important is whether this effect was clinically meaningful, and to this question Gilead did not give an affirmative answer.

The company took the unusual move of filing a separate Q&A document with the SEC, whose first question was: did PFS meet your bar for clinically meaningful? “There is a broad range of views on what is ‘clinically meaningful’ in this population. We are evaluating the data and will explore potential pathways with regulatory authorities,” the company stated.

Analysts did not take kindly to this, with Wells Fargo saying the SEC filing comment sounded negative, and suggested that the bar for clinical relevance might not have been achieved.

Tropics-02 tested Trodelvy versus chemo in third-line Her2-negative ER-positive breast cancer. It represents a major expansion play for the drug, an anti-Trop-2 antibody-drug conjugate that is already approved in third-line or later triple-negative breast cancer, and in post-chemo/PD-(L)1 urothelial bladder cancer.

The readout was especially important because Gilead had paid $21bn for Immunomedics, Trodelvy’s maker, and because several other of the group’s business development moves, including Galapagos and Kite Pharma, have failed to live up to their billing.

Absolute benefit?

Though Gilead this morning pointed out that Tropics-02 had been designed to show a 30% reduction in risk of disease progression or death, the all-important absolute benefit has not been disclosed. Analysts had expected something in the region of two or three months of added PFS benefit, so presumably many must be assuming that this has been missed.

One problem is that the landscape of available treatments for ER-positive Her2-negative breast cancer has been changing. And the signs were that Tropics-02 was heading towards a negative readout when it was enlarged from 400 to 543 patients and had its primary measures amended from PFS and objective response rate to a sole PFS primary endpoint.

Readout slipped from the fourth quarter of 2021 to January/February, and in the event even the new deadline was missed. A further black mark is that the secondary overall survival endpoint is said to have been statistically non-significant, though in fairness today’s was an interim analysis that was likely immature.

But another problem awaits Gilead in the shape of Astrazeneca/Daiichi Sankyo’s Enhertu, which recently scored a major win in Her2-low patients, a population that might overlap significantly with Trodelvy's. And Astra/Daiichi's own anti-Trop-2 ADC datopotamab deruxtecan recently began Tropion Breast-01, a phase 3 study in second/third-line Her2-negative ER-positive breast cancer.

Though virtually nothing is known about the actual result Tropics-02 has generated, the worry must be that in enlarging the trial all Gilead managed to do was ensure its success on a technicality. Those investors who still hope for a happy ending must now sweat it out until the full dataset is presented at a medical meeting.

https://www.evaluate.com/vantage/articles/news/trial-results/gileads-tropics-readout-makes-investors-sweat

Bristol leapfrogs Roche in lung cancer

 The US green light for Bristol Myers Squibb’s Opdivo plus chemo for neoadjuvant lung cancer represents one of the fastest approvals on record. The filing, based on the Checkmate-816 study, had only been accepted for review on February 28, but just four days later – over four months before the filing’s Pdufa date – the FDA has given it the thumbs up. Bristol now boasts the first ever immunotherapy for neoadjuvant NSCLC treatment, an important accolade as the company attempts to make up with perioperative Opdivo uses the ground it lost in some metastatic cancers. The neoadjuvant approval puts Opdivo ahead of Roche’s Tecentriq, which was last October greenlit for adjuvant NSCLC in PD-L1-positive patients, and Merck & Co’s Keytruda, whose Keynote-091 trial in a slightly broader adjuvant NSCLC population read out positively in January. In neoadjuvant NSCLC the next anti-PD-(L)1 data catalysts will come from Roche’s Impower-030 and Astrazeneca’s Aegean trials, both of which have seen delays to their expected readouts.

Selected anti-PD-(L)1 MAb studies in perioperative NSCLC
	Neoadjuvant NSCLC	Adjuvant NSCLC
Tecentriq	Impower-030*	Impower-010
	Readout delayed from 2021 to 2022	FDA approved in PD-L1 +ve (≥1%) stage II-IIIA disease, 15 Oct 2021
Keytruda	Keynote-671	Keynote-091 (Pearls)
	2024 readout	At interim, positive in stage IB-IIIA all-comers but not in ≥50% PD-L1 expressers
Opdivo	Checkmate-816	Checkmate-77T
	FDA approved in stage IB-IIIA all-comers, 4 Mar 2022	2023-24 readout
Imfinzi	Aegean	Mermaid-1
	Readout delayed from 2022 to 2023	2024 readout
Source: clinicaltrials.gov & company expectations of timing. *Also has an adjuvant stage.

Policy and regulation

https://www.evaluate.com/vantage/articles/news/policy-and-regulation-snippets/bristol-leapfrogs-roche-lung-cancer

Optinose breathes easy

 According to today’s phase 3 data Optinose’s steroid nasal spray Xhance significantly improved the symptoms of chronic sinusitis and opening up of the nasal passages, as shown by CT imaging, versus placebo. With nothing else on the market for this disease, Xhance might be presumed to have a clear shot – and indeed the company has previously said that some doctors already prescribe the product off-label for sinusitis. The company’s share price opened down 3%, possibly owing to Optinose’s decision to schedule a conference call discussing the data for after today’s market close, but later recovered to trade up slightly. But there are reasons for caution, including the vanishingly slight dose response; the two doses assessed in the ReOpen1 study produced near-identical average reductions in symptom score despite one dose being twice as high as the other. Chronic sinusitis represents an important opportunity for Optinose; according to Evaluate Pharma’s sellside consensus sinusitis sales are set to be almost twice those in Xhance’s approved indication, nasal polyps. A second phase 3 sinusitis study, ReOpen2, is due to report by the summer, and this needs to replicate the positive topline findings to help ease Xhance's journey to market.

https://www.evaluate.com/vantage/articles/news/trial-results-snippets/optinose-breathes-easy

Source: company presentation.

Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH) Analysts Are Cutting Their Estimates

 Shareholders in Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH) had a terrible week, as shares crashed 32% to US$10.89 in the week since its latest annual results. It looks like a positive result overall, with revenues of US$46m beating forecasts by 3.6%. Statutory losses of US$1.40 per share were roughly in line with what the analysts had forecast. The analysts typically update their forecasts at each earnings report, and we can judge from their estimates whether their view of the company has changed or if there are any new concerns to be aware of. We've gathered the most recent statutory forecasts to see whether the analysts have changed their earnings models, following these results.

earnings-and-revenue-growth

Following the latest results, Aurinia Pharmaceuticals' seven analysts are now forecasting revenues of US$136.3m in 2022. This would be a major 199% improvement in sales compared to the last 12 months. Losses are predicted to fall substantially, shrinking 50% to US$0.64. Before this latest report, the consensus had been expecting revenues of US$178.3m and US$0.59 per share in losses. So there's been quite a change-up of views after the recent consensus updates, withthe analysts making a serious cut to their revenue outlook while also expecting losses per share to increase.

The consensus price target fell 16% to US$27.71, with the analysts clearly concerned about the company following the weaker revenue and earnings outlook. Fixating on a single price target can be unwise though, since the consensus target is effectively the average of analyst price targets. As a result, some investors like to look at the range of estimates to see if there are any diverging opinions on the company's valuation. There are some variant perceptions on Aurinia Pharmaceuticals, with the most bullish analyst valuing it at US$34.00 and the most bearish at US$18.00 per share. There are definitely some different views on the stock, but the range of estimates is not wide enough as to imply that the situation is unforecastable, in our view.

These estimates are interesting, but it can be useful to paint some more broad strokes when seeing how forecasts compare, both to the Aurinia Pharmaceuticals' past performance and to peers in the same industry. It's clear from the latest estimates that Aurinia Pharmaceuticals' rate of growth is expected to accelerate meaningfully, with the forecast 199% annualised revenue growth to the end of 2022 noticeably faster than its historical growth of 86% p.a. over the past five years. By contrast, our data suggests that other companies (with analyst coverage) in a similar industry are forecast to grow their revenue at 12% per year. Factoring in the forecast acceleration in revenue, it's pretty clear that Aurinia Pharmaceuticals is expected to grow much faster than its industry.

The Bottom Line

The most important thing to note is the forecast of increased losses next year, suggesting all may not be well at Aurinia Pharmaceuticals. They also downgraded their revenue estimates, although industry data suggests that Aurinia Pharmaceuticals' revenues are expected to grow faster than the wider industry. The consensus price target fell measurably, with the analysts seemingly not reassured by the latest results, leading to a lower estimate of Aurinia Pharmaceuticals' future valuation.

With that in mind, we wouldn't be too quick to come to a conclusion on Aurinia Pharmaceuticals. Long-term earnings power is much more important than next year's profits. We have estimates - from multiple Aurinia Pharmaceuticals analysts - going out to 2024, and you can see them free on our platform here.

https://finance.yahoo.com/news/aurinia-pharmaceuticals-inc-nasdaq-auph-093752819.html

Spectrum: Positive Data for Poziotinib in Lung Cancer

 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, today announced the presentation of safety and efficacy results from Cohort 4 of the ZENITH20 clinical trial. This data is from 70 first-line patients with non-small lung cancer (NSCLC) with HER2 exon 20 insertion mutations who received 16 mg daily, given as 16 mg once daily (48 patients) or 8 mg twice daily (22 patients) of oral poziotinib. These results showed a confirmed objective response rate (ORR) of 41% (95% CI:30%-54%), as evaluated centrally by an independent image review committee using RECIST 1.1 criteria. The evaluable patient population showed an ORR of 50%. The study met its primary endpoint as the observed lower bound of 30% exceeded the pre-specified lower bound of 20%. The safety profile was consistent with the TKI class. The data is part of an oral presentation at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Congress 2022 being held virtually March 7-8, 2022.

"Cohort 4 from our ZENITH 20 study demonstrated positive results for treatment naïve lung cancer patients harboring HER2 Exon 20 insertion mutations. There is currently no approved treatment for NSCLC patients with these mutations," said Francois Lebel, M.D., Chief Medical Officer of Spectrum. "We are encouraged by these findings and look forward to further discussions with the FDA on the regulatory path forward."

The presentation is available on the Spectrum Pharmaceuticals website at: https://investor.sppirx.com/index.php/events-and-presentations.

https://finance.yahoo.com/news/spectrum-pharmaceuticals-presents-positive-data-110000068.html

Harpoon Therapeutics Granted Orphan Drug Tag for Lung Cancer Therapy

 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for HPN328, a delta like ligand 3- (DLL3) targeting TriTAC®, for the treatment of small cell lung cancer (SCLC). A Phase 1/2 clinical trial is currently ongoing for HPN328 in the SCLC patient population.

https://finance.yahoo.com/news/harpoon-therapeutics-granted-orphan-drug-123000436.html