AstraZeneca cannot breathe easy despite first triplet approval

Astrazeneca hopes that its new COPD triplet can gain share from Glaxosmithkline’s rival, but it is not planning a price war.

Astrazeneca now has a COPD triplet, Breztri Aerosphere, to compete with Glaxosmithkline’s Trelegy Ellipta. But Astra is not planning to go hard on price, the company told Vantage, and instead will rely on clinical data to grab market share.

Breztri Aerosphere, previously known as PD010, bagged its first approval today, in Japan. Still, investors in the product’s originator, Pearl Therapeutics, will have to wait a bit longer for their payday: their first milestone of $150m is not due until approval in the US, where a decision is expected in 2020.

This also puts Astra’s inhaler well behind Trelegy Ellipta, which got the FDA nod for COPD in 2017, and has since become a surprise success story for Glaxo. Both inhalers combine a long-acting beta agonist (LABA), long-acting muscarinic antagonist (LAMA) and corticosteroid in a single inhaler.

Competitive?

Despite Glaxo’s head start, its rival believes that it can claw back ground. Tom Keith-Roach, vice-president of Astra’s respiratory division, would not give details of Breztri Aerosphere’s price in Japan or elsewhere, but said this would not be a major point of differentiation, and instead highlighted the product’s “highly competitive clinical profile” and potentially more patient-friendly device.

He pointed to the pivotal Kronos trial, which found a 52% reduction in the rate of moderate or severe COPD exacerbations with Breztri Aerosphere compared with Astra’s marketed LAMA/LABA Bevespi Aerosphere; there was also a 17% reduction versus Astra’s LABA/steroid inhaler Symbicort.

According to its label, Trelegy Ellipta reduced rates of moderate to severe exacerbations by 25% compared with Anoro Ellipta, Glaxo’s LAMA/LABA combo, and by 15% versus Breo Ellipta, Glaxo’s LABA/steroid doublet.

Still, the use of different comparators makes it hard to ascertain whether Breztri Aerosphere is truly superior to Trelegy Ellipta here. And stacking Breztri Aerosphere up against Trelegy Ellipta on measures of respiratory function like forced expiratory volume in one second (FEV₁) is even trickier. As well as the usual issues with cross-trial comparisons, and different control medications, the task is made more difficult by the use of slightly different outcome measures.

The only way to answer the question of the triplets’ respective merits definitively would be a head-to-head study, but Astra said it was not planning one, and presumably neither is Glaxo.

BREZTRI AEROSPHERE VS TRELEGY ELLIPTA
Project	Company	Status	Reduction in exacerbations vs LAMA/LABA	2024e sales ($m)
Breztri Aerosphere	Astrazeneca	Approved Japan; filed elsewhere	52%	$400m
Trelegy Ellipta	Glaxosmithkline	Approved US, EU, Japan	25%	$1,584
Source: EvaluatePharma, company releases, product label.

Mr Keith-Roach also contended that patients might prefer Breztri Aerosphere, which comes in a pressurised metered-dose inhaler, over Trelegy Ellipta, which is delivered via a dry-powder device.

Many COPD patients initially receive reliever therapies given via pressurised metered-dose inhalers, so are more familiar with these, he argued.

He added that dry-powder inhalers were not always suitable for patients with more severe COPD, as these might lack the lung function needed to draw dry powder into the lungs.

Both companies are also evaluating their products in asthma where, again, Glaxo is ahead after recently reporting a win in the phase III Captain trial. Meanwhile, Breztri Aerosphere is in a phase II dose-ranging study in asthma, but Mr Keith-Roach would not say when Astra was expecting data.

The coming months could give some clues about whether Breztri Aerosphere has enough of an edge to challenge its more entrenched rival. The sellside certainly thinks that Glaxo will retain its upper hand: EvaluatePharma consensus forecasts 2024 sales of $1.6bn for Trelegy Ellipta and just $400m for Breztri Aerosphere.

Perhaps if Astra wants to build a bigger franchise for its triplet it might have no choice but to compete on price.

https://www.evaluate.com/vantage/articles/news/policy-and-regulation/astra-cannot-breathe-easy-despite-first-triplet

Allergan, following years of turmoil and resistance, heads for split

Allergan has grappled with numerous setbacks and plenty of investor uproar in recent years, but so far it’s resisted serious change. But now, the company seems ready to embark on a split, according to analysts.

In a Tuesday note, Evercore ISI analyst Umer Raffat wrote that following a recent call with the company’s general counsel, “I walked away with the sense that Allergan is heading towards a split and may likely lay out timelines.” Raffat wrote that he thinks the company will announce the split on the second-quarter conference call. Allergan’s shares jumped 4% Tuesday after the note amid a yearslong downward trend.

Also on the call, Allergan’s VP of investor relations and strategic initiatives Manisha Narasimhan said there’s a “continued sense of urgency from both management and the board for ways which we think would unlock value.”

“In terms of timing, we’re working as quickly as we can, and we hope to be in a position to be able to make an announcement over the next couple of months,” she added.

The company’s shares have tumbled about 65% since the summer of 2015, fueling analyst and investor pressure for change. Allergan has resisted a split in favor of cost-cutting and other measures, but so far its efforts have not improved its fortunes.

In lieu of a breakup, activist investors have pushed to split up Allergan’s CEO and chairman roles—both currently held by Brent Saunders. David Tepper, manager of hedge fund Appaloosa, queued up a battle that Allergan won in early May as shareholders sided with the company and against Tepper’s role-split proposal.

But soon after the vote, Saunders said the company was reviewing “all options” to turn things around—and doing it with a sense of urgency. Now, Raffat believes a split announcement is coming within the next “couple of months.”

In his own note, RBC Capital Markets analyst Randall Stanicky—who has been advocating a breakup for years—wrote that the possibility of a split announcement “shouldn’t come as a surprise” given the company’s recent history.

“The reality is we’re not sure what else management can do at this point with stock pressure persisting and sentiment as low as it is,” he added. “Street attention on break-up is picking up as this remains the primary bull case for the stock.”

The “growth company” created from a split would likely include aesthetics, central nervous system treatments and eye care, Stanicky wrote. Gastrointestinal, primary care and women’s health—a unit Allergan tried unsuccessfully to hive off—would go into the “mature company,” he added. One question the analyst raised is who would run the growth company, as investor unease around Saunders and the current management team has swelled recently.

Meanwhile, regulatory and development hurdles have made matters worse for the Dublin drugmaker. After Allergan’s cost-cutting didn’t improve share prices, the company explored the women’s health sale. But after the FDA rejected uterine fibroids treatment Esmya, which Allergan had billed as a potential blockbuster, the company called the sale off. It’s also suffered recent pipeline setbacks, including a triple flop on closely watched depression drug rapastinel. And 2017’s controversial tribal patent deal on Restasis has lingered with the company through a blow from the Supreme Court.

Tepper, in pushing for management changes, said the current team is responsible for more than $13 billion in balance sheet write-downs in recent years, plus “embarrassing legal initiatives,” a “failed acquisition strategy resulting in an underperforming product pipeline,” a lower stock price and “stunningly excessive” management compensation.

https://www.fiercepharma.com/pharma/following-years-turmoil-and-resistance-allergan-preparing-to-split-analyst

Stoke Therapeutics Opens Above IPO Price

Stoke Therapeutics, Inc. NASDAQSTOK opened Wednesday morning at $27.21 per share. The company priced 7 million shares of common stock at $18 per share.

JPMorgan, Cowen, Credit Suisse and Cannacord Genuity are the underwriters for the offering. As Stoke qualifies as an “emerging growth company” and a “smaller reporting company” under the federal securities laws, it has the leeway to comply with certain reduced disclosure norms.

The Massachusetts-based early-stage biopharma company was founded in June 2014 and pioneers a new way of treating underlying causes of several genetic diseases by precisely upregulating protein expression.

Stoke is developing novel antisense oligonucleotide medicines targeting RNA and modulate precursor-mRNA, developed using its proprietary technology platform names TANGO – Targeted Augmentation of Nuclear Gene Output.

https://www.benzinga.com/general/biotech/19/06/13944139/stoke-therapeutics-opens-above-ipo-price

OrthoPediatrics started at Buy by Needham

Target $53

https://www.benzinga.com/stock/KIDS/ratings

Karyopharm Updates Phase 2b Data at Conference on Malignant Lymphoma

Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today reported updated results from the Phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study evaluating selinexor, the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue and CAR-T (chimeric antigen receptor modified T cell) therapy.  The data were highlighted in an oral presentation at the 2019 International Conference on Malignant Lymphoma (ICML) being held June 18-22, 2019, in Lugano, Switzerland.

Top-line results for the SADAL study were previously presented at the American Society of Hematology (ASH) 2018 Annual Meeting in December 2018.   The results being presented at ICML remain consistent with those reported at ASH and include efficacy results from the final 12 patients who had not reached their first response assessment in time to be included in the previously released top-line efficacy analyses.  For the SADAL study’s primary endpoint, single-agent selinexor achieved an overall response rate (ORR) of 28.3%.  Two additional patients achieved a complete response (CR) since the ASH presentation for a total of 13 CRs and a CR rate of 10.2% in these patients with heavily pretreated relapsed or refractory DLBCL.  Key secondary endpoints included a median duration of response (DOR) in the responding patients of 9.2 months and median overall survival (OS) across the entire study population of 9.0 months.

https://www.globenewswire.com/news-release/2019/06/19/1871363/0/en/Karyopharm-Reports-Updated-Data-from-the-Phase-2b-SADAL-Study-at-the-2019-International-Conference-on-Malignant-Lymphoma.html

Portola Presents Interim Phase 2 Data on Follicular Lymphoma Combo

– Interim Phase 2a Data Highlight Efficacy and Safety Results of Cerdulatinib Alone and in Combination with Rituximab –

– Data Presented at the 15th International Conference on Malignant Lymphoma (ICML) –

Portola Pharmaceuticals, Inc.^® (Nasdaq: PTLA) today announced new interim results from the Company’s ongoing Phase 2a study of cerdulatinib, an investigational, oral SYK/JAK inhibitor, in patients with relapsed/refractory follicular lymphoma (FL) receiving cerdulatinib alone or in combination with rituximab. Data were presented this month in a poster session at the 24^th Congress of the European Hematology Association (EHA) in Amsterdam (June 13-16) and during an oral session today at the 15^th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (June 18-22).

Data included safety and efficacy findings for 40 patients who received single agent cerdulatinib at 30 mg twice daily (with the exception of two patients who initiated treatment at 35 mg) and 17 patients who received cerdulatinib at 30 mg twice daily in combination with a standard dosing regimen of rituximab. The number of prior treatment regimens including anti-CD20 antibody, bendamustine and anthracyclines ranged from one to nine, with a median of three.

Among the 40 patients in the cerdulatinib-only cohort, the objective response rate (ORR) was 45%; five patients (13%) achieved a complete response (CR), 13 patients (33%) achieved a partial response (PR) and 10 patients (25%) achieved stable disease (SD). Of the 27 patients with a PR or SD at first evaluation in the single agent cerdulatinib cohort, 17 (63%) had a further reduction in tumor volume at a subsequent efficacy evaluation. To date, 15 of the 40 patients (38%) in the cerdulatinib-only cohort have been on study drug for at least 10 months.

Among the 13 patients evaluated for efficacy in the cerdulatinib and rituximab combination cohort, the ORR was 62%; one patient (8%) achieved a CR, seven patients (54%) achieved a PR and five patients (39%) achieved SD. To date, 10 of the 13 patients have been on study drug from three to 10 months.

https://www.prnewswire.com/news-releases/portola-presents-new-interim-data-on-its-oral-sykjak-inhibitor-cerdulatinib-in-heavily-pre-treated-patients-with-relapsedrefractory-follicular-lymphoma-300870911.html

Sorrento has positive resiniferatoxin data

Sorrento Therapeutics (NASDAQ:SRNE) announces that the Phase 1b study has generated positive data and met the day 84 goals set for the resiniferatoxin (RTX) program to advance the investigational drug product into Phase 3 clinical trials.

This study is to assess the safety and preliminary efficacy of intra-articular administration of resiniferatoxin or saline control (as placebo group) for the treatment of moderate to severe pain due to osteoarthritis of the knee.

45 patients were treated in Phase 1b trial to date. 37 patients received RTX and 8 patients received saline (pooled as placebo group).

Most adverse events were expected and included pain, hypertension and tachycardia. These events were moderate and resolved in less than a day.

At the time of update, 30 patients were assessed at day 84.

Further analysis comparing RTX to saline response highlights persistent effect beyond day 84.

Two dose levels will be further expanded to confirm the final dose for upcoming Phase 3 studies.

https://seekingalpha.com/news/3472329-sorrento-plus-5-percent-positive-resiniferatoxin-data