Tag: Business of Medicine

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4 DRUG AND BIOTECH STOCKS AWAITING FDA APPROVAL IN JULY 2017

FDA Decisions in July

by Kinjel Shah

http://bit.ly/2KqNeLd

We are into the second half of the year. It’s time to analyze how the first half turned out to be for pharma and biotech stocks in terms of FDA decisions. The regulatory body approved 17 novel drugs in the first half of 2018, which is less than the year-ago period figure of 23. However, with several FDA decision lined up for the second half, a higher number of drugs could be approved in the rest of the year.

Key FDA approvals in the first half included Amgen/Novartis’s first CGRP antibody Aimovig/erenumab for prevention of migraine, Johnson & Johnson’s next-generation oral androgen receptor (“AR”) inhibitor Erleada (apalutamide) for pre-metastatic prostate cancer (CRPC), Vertex Pharmaceuticals’ third medicine to treat the underlying cause of CF, Symdeko, which is a combination of tezacaftor and ivacaftor and BioMarin Pharmaceuticals’ Palynziq to treat phenylketonuria (PKU).

With the drug development process being lengthy and time-consuming, plus requiring the utilization of a lot of funds and resources, key pipeline events including data readouts and regulatory updates are of paramount importance and could act as major catalysts.

Let’s take a look at a few important regulatory events scheduled for the month of July.

Drug and Biotech Stocks Awaiting FDA Decisions in July: Indivior (INVVY)

FDA Decision on Indivior’s Schizophrenia Injection RBP-7000: On Jul 28, the FDA is expected to give its decision on Indivior‘s RBP-7000, which has been developed for the treatment of schizophrenia.

RBP-7000 is a once-monthly injectable risperidone given using the Atrigel delivery system. Indivior is a Zacks Rank #3 (Hold) stock.

Drug and Biotech Stocks Awaiting FDA Decisions in July: Progenics (PGNX)

Progenics Pharmaceuticals’ Azedra Review: Progenics new drug application (NDA), looking to get its pipeline candidate, Azedra approved for the treatment of patients suffering from malignant rare neuroendocrine tumors — pheochromocytoma and paraganglioma — is under review.

The FDA is expected to give its decision on Jul 30, after a three-month delay from the previous FDA action date in March. Azedra was added to Progenics’ portfolio with the acquisition of Molecular Insight Pharmaceuticals in 2013.

Drug and Biotech Stocks Awaiting FDA Decisions in July: Insys Therapeutics (INSY)

Decision on Insys Therapeutics’ Pain Candidate: On Jul 28, the FDA is also expected to give its decision on Insys Therapeutics’ buprenorphine sublingual spray for moderate-to-severe acute pain. It is important to remember that in May an FDA advisory committee voted against its approval.

The company had filed a new drug application (“NDA”) in September last year based on positive data from a pivotal study on the candidate. The FDA accepted the NDA for review in December assigning a PDUFA date of Jul 28, 2018.

It is quite possible that the unfavorable vote by the committee may influence the FDA’s decision and delay the approval of the drug.

Drug and Biotech Stocks Awaiting FDA Decisions in July: GlaxoSmithKline (GSK)

Will an FDA Panel Back New Indication for Glaxo’s Nucala?: Toward the end of the  month, an FDA panel is expected to give its opinion on GlaxoSmithKline‘s  label expansion filing for eosinophilic asthma drug, Nucala (mepolizumab) for a  new indication –  chronic obstructive pulmonary disease (COPD). With the latest filing, Glaxo is looking to get Nucala approved as an add-on maintenance treatment of COPD with an eosinophilic phenotype.

Nucala is presently approved for treating severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (“EGPA”). Glaxo hadfiled a supplemental Biologics License Application (sBLA) to the FDAfor label expansion of Nucala to include use in COPD in November last year.

Although the FDA takes the recommendations of its panels/advisory committee into account while reviewing applications, it is not bound to follow the same.

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CAN A NEW DEVEOPMENT MODEL PREVENT COSTLY PHASE III DRUG DEVELOPMENT FAILURES?

by Daniel Dupuis

Attaining FDA approval for a new drug is certainly the ultimate goal of any drug research initiative. Accelerating that process can not only prove to be beneficial to patients, but is also a key component of increasing the return on investment for any entity that has a vested interest in a new medication.

Due to decreased productivity, the internal return on investment for research and development within the pharmaceutical industry has been sliding for years, and reports have indicated that it is already below break-even when the cost of capital is included and it will continue to fall in the ensuing years.

Pharmaceutical companies share the characteristics of many large, multi-national corporations that have enjoyed substantial profits for decades in that they suffer from corporate paralysis. The ramifications of this malady have resulted in them being slow to adopt new development models.

One methodology that can offer great benefits to pharm aceutical companies is the patient-derived xenograft (PDX) model. Oncology has been the recipient of the largest share of venture capital over the last few years, with immuno-therapy being an area of considerable focus and the PDX model is especially applicable to this sector.

In a PDX model, a live human tumor is grafted onto an immuno-deficient mouse and the results have demonstrated that it very closely replicates the therapeutic responses that take place in human trials. This allows companies to predict outcomes in the early stages of development and make the decision to abandon, or alter the molecular structure of a drug, long before the start pf pivotal Phase III trials.

What is the value of such a model? Companies often spend $700 to $800 million in development before they reach the pivotal Phase III trials. One only has to scan recent biotech news stories to quickly realize that adoption of PDX models, when applicable, will soon be viewed as the preferred methodology.

On April 6th of this year, shares of Incyte plummeted 23% in one day, while Merck shares fell 2.5%, on the news that the results of the Phase III trial of the combination of Merck’s Keytruda and Incyte’s epacadostat failed to show a significant improvement in efficacy over Keytruda as a stand-alone therapy. This unexpected outcome also cast doubt on other similar drugs in development and NewLInk Genetics saw its stock plummet by 42.6%.

A similar scenario befell Jounce Therapeutics on June 4th of 2018 as its stock fell 38% in one day when their drug candidate, JTX-2011, failed to deliver robust patient responses, either as a stand-alone treatment, or in combination with Opdivo (Bristol-Myers Squibb), against a range of solid tumor cancers.

The aim of immuno-therapy is to deliver efficacy, while either minimizing, or eliminating, the debilitating side effects of current cancer medications. In light of the precipitous drop in stock price of the aforementioned companies, recent criticism has now focused on the fact that none of the new formulations had any demonstrated efficacy as stand-alone therapies prior to being combined with current standard of care drugs.

There are current medications that are already in the marketplace, or in development, that have implemented the PDX model with unparalleled success. Of note, is that these single medications have been shown to be effective against several forms of cancer, which is a direct result of PDX models identifying biomarkers of therapeutic responses and allowing for numerous tests to be conducted at a cost effective rate.

Abraxane™, a cancer drug developed by Celgene, effectively utilized PDX models. It is a protein-bound paclitaxel in an injectable form that is used to treat breast cancer, lung cancer and pancreatic cancer. In June 2010, positive results were published for a Phase III trial for NSCLC (non-small cell lung cancer) when compared to solvent-based paclitaxel and Abraxene™ was approved in 2012 for the treatment of NSCLC. In September of 2013 it received approval for use in treating advanced pancreatic cancer as a less toxic alternative to FOLFIRINOX.

An immuno-oncology drug candidate that is now poised to enter a Phase II/III trial is perhaps the best example of how a PDX model was used to identify therapeutic responses for prostate cancer and also for its pipeline development. Aneustat™, a multivalent foundational drug developed by Omnitura Therapeutics, used a PDX model to derive their pre-clinical data proving Aneustat’s efficacy, both as a monotherapy and as a combination therapy with docetaxel, while exhibiting reduced toxicity, side effects, and drug resistance.   

The high rate of predictability of the PDX cancer model makes their upcoming pivotal trial much more of a foregone conclusion than a high level risk.

HOW A SHIFT IN DEVELOPMENT STRATEGY MAY AFFECT INVESTMENT

Venture capital over the last few years has focused almost exclusively on early-stage companies, while limiting investment in mid or late stage biotech companies. This is understandable in that the chances of successfully completing Phase III trials to the satisfaction of the FDA are 1 in 5. The emergence of the PDX model, however, may dramatically change this assessment as it directly mirrors what may transpire in Phase III trials, but in the early stages, when it’s cost effective. Would a a venture capitalist be far more willing to invest in a drug prior to a Phase III trial if their predictive model indicated their successful outcome was probable rather doubtful?

Some companies may be hesitant to utilize the PDX cancer model, as the results may not be favorable and companies have attracted substantial investment and/or shareholder capital long before proof of concept. Now that PDX models are known to accurately mirror therapeutic responses in human trials, however, investors may ultimately demand their inclusion.

Considering the enormous cost of the aforementioned Phase III failures, special attention should be focused on the utilization of PDX models and the drugs that are developed utilizing this strategy. It is ultimately cost effective and will be of great benefit to patients that are in need of safe and effective new therapies.

*The number of PDXs evaluated

The Predictive Value of PDXs for Clinical Outcome

A recent pooled study has been published that provides a clear relationship between PDXs and human clinical trials. In fact, it not only indicates how efficacious a medication may be, but also allows for targeting specific characteristics. For example, the study of non-small cell lung cancer indicated that Gefitinib was effective, but only with the EGFR Exon19 Del mutation, while EGFR wild-types were rendered ineffective. This directly correlates with the results accrued from the human studies. These results are indicative of the value of the PDX model, as it allows for the development of new drugs within a narrow parameter and provides valuable information in the early stages of development.

CONCLUSION:

It is clear that the utilization of PDX models in the development of cancer drugs is an increasingly valuable tool that is not only cost effective, but will help companies to more quickly develop medications that have considerably better odds of being ultimately approved.